A rare but serious complication of continuous ambulatory peritoneal dialysis: delayed perforation of the colon by the Tenckhoff catheter

DOI: 10.12809/hkmj144419
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
A rare but serious complication of continuous ambulatory peritoneal dialysis: delayed perforation of the colon by the Tenckhoff catheter
PY Chu, FRCR; KL Siu, FRCR
Department of Diagnostic Radiology, Tuen Mun Hospital, Tuen Mun, Hong Kong
 
Corresponding author: Dr PY Chu (idleadam@hotmail.com)
 
 Full paper in PDF
 
Case report
A 68-year-old male had end-stage renal failure due to diabetes mellitus. He underwent Tenckhoff catheter insertion in 2013 for continuous ambulatory peritoneal dialysis (CAPD). The catheter was flushed regularly once a week and was functional in the first 2 months following insertion.
 
The catheter became blocked 2 months following insertion after an episode of CAPD peritonitis. Peritoneal dialysate showed scanty growth of Stenotrophomonas (Xanthomonas) maltophilia. Kidney, ureter, and bladder X-ray (KUB) was ordered to identify catheter tip position that was subsequently revealed to be in the central part of the pelvic cavity (Fig 1a). The cause of blockage was suspected to be omental wrap. Omentectomy was planned and the Tenckhoff catheter was left in situ; CAPD peritonitis was successfully treated with antibiotics and the patient was discharged. The peritoneal membrane was rested for 2 weeks and the patient maintained on temporary twice-weekly haemodialysis.
 

Figure 1. (a) Initial kidney, ureter, bladder X-ray showing the Tenckhoff catheter in the central pelvic cavity (arrow), with coiling of catheter tip; (b) abdominal X-ray 5 months after insertion demonstrating inferior migration of the catheter tip with loss of tip coiling (arrow); (c) pelvic X-ray a few days after (b) showing the Tenckhoff catheter passing out through anus (arrow); (d) contrast-enhanced computed tomography of abdomen and pelvis showing Tenckhoff catheter perforation through the sigmoid colon (arrow)
 
The patient was admitted to Tuen Mun Hospital again in early 2014 because of fall. Computed tomographic (CT) brain revealed a significant left acute subdural haemorrhage. Urgent craniotomy with clot evacuation was performed. At that time, abdominal X-ray demonstrated inferior migration of the catheter tip with loss of coiling of the distal tip (Fig 1b). A few days later, the tip of Tenckhoff catheter was noticed in the anus of the patient. Follow-up KUB confirmed the clinical finding (Fig 1c).
 
The patient had no symptoms or signs of acute peritonitis. Contrast-enhanced CT abdomen and pelvis confirmed perforation of the Tenckhoff catheter through the sigmoid colon with the tip in the anus (Fig 1d).
 
The contrast-enhanced CT demonstrated Tenckhoff catheter perforation through the sigmoid colon (Fig 2a) with soft-tissue fibrosis around the catheter at the site of the perforation (Fig 2b). There was no ascites or inflammatory fluid collection. Contrast enema showed no evidence of contrast extravasation.
 

Figure 2. Contrast-enhanced computed tomographic abdomen and pelvis
(a) Tenckhoff catheter perforation through the sigmoid colon (arrow), and (b) soft-tissue fibrosis (arrow) around the catheter at the site of the perforation are shown
 
The patient became chair-bound after the head injury. It was decided not to remove or reposition the Tenckhoff catheter or perform omentectomy. The rectal side of the catheter was cut short.
 
Discussion
The pathogenesis of late perforation of the bowel has been proposed to involve intimate contact between the peritoneal catheter and the intestinal wall. The continuous pressure causes local ischaemia, eventually leading to erosion, laceration, and frank perforation.1 Lack of fluid in the peritoneal space after cessation of CAPD predisposes to pressure-induced necrosis because of loss of the fluid cushion.2 3 In our patient, perforation was unlikely when the catheter was in daily use because it did not come into continuous close contact with the bowel for any long period of time.4
 
In most previous studies, delayed perforation of the bowel was associated with acute peritonitis.1 3 5 6 Kagan and Bar-Khayim1 reviewed the publications from 1980 to 1995 and identified 24 cases of bowel perforation during the study period. All cases were associated with acute peritonitis, with 29% mortality and significant morbidity. The age of patients ranged from 22 to 80 years, with no gender predominance. The time to bowel perforation also ranged broadly from 0.5 to 96 months after initiation of dialysis. Sigmoid was the most common site of perforation, accounting for 14 of the 24 cases. Asymptomatic delayed perforation of the bowel by Tenckhoff catheter was rarely reported.7 8
 
Our patient had acute peritonitis in late 2013. The KUB showed normal position of Tenckhoff catheter (Fig 1a) . Since the Tenckhoff catheter was not functioning, omental wrap was suspected.
 
Later X-rays revealed progressive inferior migration of the catheter and loss of coiling of the catheter tip, suggesting perforation of the bowel (Figs 1b and 1c). The CT abdomen and pelvis confirmed perforation of the sigmoid by the Tenckhoff catheter in addition to soft-tissue fibrosis around the catheter tip (Figs 1d and 2).
 
In our case, in addition to the lack of peritoneal dialysis fluid, there were probably peritoneal adhesions arising from previous peritonitis that resulted in decreased bowel mobility. This in turn created a predisposition to impingement of bowel loops by the Tenckhoff catheter that subsequently led to pressure erosion and perforation.
 
The patient had no clinical or radiological evidence of peritonitis, possibly due to plugging of the bowel perforation site by the catheter and later sealed off by inflammatory adhesion and fibrosis. Thus, there was no leakage of faecal material from the sigmoid into the peritoneal cavity to incite inflammation and consequent faecal peritonitis. Occasionally the omentum can also surround and wall off focal inflammation to prevent extension of the inflammation to involve the rest of the peritoneal cavity, as may be seen in the formation of phlegmon or an abscess in ruptured acute peritonitis.
 
We present a rare but clinically important case of delayed perforation of the bowel by Tenckhoff catheter. According to this case report and several reported cases, regular flushing of the dialysis catheter and early removal if not in use (dysfunctional or not required) may help prevent this complication.
 
Declaration
No conflicts of interest were declared by the authors.
 
References
1. Kagan A, Bar-Khayim Y. Delayed decubitus perforation of the bowel is a sword of damocles in patients on peritoneal dialysis [Letter]. Nephron 1996;74:232-3. Crossref
2. Brady HR, Abraham G, Oreopoulos DG, et al. Bowel erosion due to a dormant peritoneal catheter in immunosuppressed renal transplant recipients. Perit Dial Int 1988;8:163-5.
3. Rambausek M, Zeier M, Weinreich T, Ritz E, Rau J, Pomer S. Bowel perforation with unused Tenckhoff catheters. Perit Dial Int 1989;9:82.
4. Parvin SD, Beaman M. Ileal erosion by the Tenckhoff catheter. Perit Dial Bull 1985;5:82.
5. Valles M, Cantarell C, Vila J, et al. Delayed perforation of the colon by a Tenckhoff catheter. Perit Dial Bull 1982;2:190.
6. Thibodeaux LC. Bowel perforation associated with continuous ambulatory peritoneal dialysis. Nephron 1995;70:265. Crossref
7. Saweirs WW, Casey J. Asymptomatic bowel perforation by a Tenckhoff catheter. Perit Dial Int 2005;25:195-6.
8. Balaji V, Digard N, Wise MH. Delayed bowel erosion due to functioning chronic ambulatory peritoneal dialysis catheter. Nephrol Dial Transplant 1996;11:368-9. Crossref

Primary gestational choriocarcinoma of the vagina: magnetic resonance imaging findings

Untitled Document
DOI: 10.12809/hkmj144362
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Primary gestational choriocarcinoma of the vagina: magnetic resonance imaging findings
T Wong, FRCR; Eliza PY Fung, FHKCR, FHKAM (Radiology); Alfred WT Yung, FHKCR, FHKAM (Radiology)
Department of Radiology, Princess Margaret Hospital, Laichikok, Hong Kong
 
Corresponding author: Dr T Wong (gloria_wong@live.com)
 
 Full paper in PDF
 
Case report
A 33-year-old nulligravid Filipino woman was admitted to the gynaecology ward of Princess Margaret Hospital in April 2014, with lower abdominal pain and recurrent retention of urine. Her pregnancy test was positive. Per-vaginal examination revealed a 4-cm firm, fixed, and wide-based vaginal mass with smooth wall over the upper anterior vagina. Bedside transabdominal ultrasonography confirmed a 4.5-cm solid mass in the anterior vagina and a 3.5-cm intramural fibroid over the left side of the uterus. No adnexal mass or free fluid was seen. Beta human chorionic gonadotropin (β-hCG) level was elevated to 270 743 IU/L (reference level, <5.0 IU/L for non-pregnant women), and repeated checking 3 days later was 253 957 IU/L. Alpha-fetoprotein, carcinoembryonic antigen, and Ca-125 were negative. A urologist was consulted and the patient underwent flexible cystoscopy that revealed indentation of the urinary bladder by an external mass. Mild erythematous changes were visualised at the right urinary bladder base. Biopsy revealed inflammation but no malignant cells.
 
Magnetic resonance imaging (MRI) of the pelvis revealed a 4.8 cm x 5.2 cm x 4 cm (craniocaudal x anteroposterior x transverse) mass located at the anterior aspect of the vagina. It was hypointense with a faint hyperintense rim on T1-weighted images (Fig 1a) and heterogeneously hyperintense with hypointense rim on T2-weighted images (Fig 1b). Peripheral enhancement was observed while the central part remained non-enhanced (Figs 1c and 1d). Part of the mass closely abutted the cervix and urinary bladder, where intervening fat planes could not be well-delineated. The urinary bladder wall was trabeculated. Dilated enhancing tortuous tubular structures were seen at the left adnexal region and numerous signal void foci were observed at the uterine wall. These were due to the presence of high-flow vasculatures related to tumour hypervascularity (Figs 1e to 1h). There was also an incidental finding of a predominantly T2 hypointense non-enhancing intramural fibroid at the posterior uterine fundus (Figs 1b and 1d). No ovarian mass was detected and no intra-uterine gestational sac or ectopic pregnancy.
 

Figure 1. Magnetic resonance imaging (MRI) scans
(a) A T1-weighted axial image showing approximately 4-cm hypointense mass with a slightly hyperintense rim in anterior aspect of the vagina (white arrow). (b) The mass (white arrow) is heterogeneously hyperintense with hypointense rim on T2-weighted images on sagittal plane. Note the incidental finding of a predominantly T2 hypointense fibroid at posterior uterine fundus (black arrow). (c) Axial and (d) sagittal post gadolinium contrast T1-weighted images showing enhancement of the peripheral zone and non-enhancing central zone (white arrows). The fibroid at posterior uterine fundus is again seen on sagittal image (black arrow). (e) Coronal, (f) sagittal, and (g) axial T2-weighted images showing dilated tortuous tubular structures at left adnexal region (white arrows) and numerous signal void foci at uterine wall (open arrows). These were suggestive of hypervascularity of the tumour with the presence of high-flow vasculatures. (h) A sagittal post gadolinium contrast T1-weighted image showing avid enhancement of the high-flow vasculatures (black arrows)
 
Later examination under anaesthesia revealed that the lower part of the vaginal lesion had ruptured. Excision of part of the vaginal lesion was performed. Tissue frozen section confirmed it to be choriocarcinoma with no other germ cell component. DNA polymorphism analysis was performed in a microsatellite analysis using six markers by extracting DNA from the microdissected tumour cells, then comparing it with normal DNA extracted from a peripheral blood sample. The result favoured gestational choriocarcinoma. In addition, chest X-ray revealed multiple ill-defined opacities in both lungs, measuring about 0.8 to 1.2 cm in size (Fig 2a).
 

Figure 2. Frontal chest radiographs of the patient
(a) Before treatment multiple ill-defined small opacities in both lungs (arrows) are shown, representing pulmonary metastases, and (b) radiograph after initiation of chemotherapy showing interval regression of the lesions
 
The patient was diagnosed with primary gestational choriocarcinoma of the vagina with lung metastases, and suspicious infiltration of the urinary bladder and cervix. She was further managed at the gynae-oncology specialist centre and given chemotherapy (etoposide, methotrexate, actinomycin, and cisplatinum). The β-hCG level dropped to 5604 IU/L with interval regression of the pulmonary nodules after initiation of chemotherapy (Fig 2b).
 
Discussion
Gestational trophoblastic disease comprises a wide spectrum of benign/premalignant to malignant conditions and includes hydatidiform mole (complete or partial), invasive mole, choriocarcinoma, and placental-site trophoblastic tumour. The incidence varies in different countries with the highest rate noted in South-East Asia. The cause of such variation is not well understood.1 Choriocarcinoma is a malignant form of gestational trophoblastic neoplasia, and generally arises in the uterine corpus of women of reproductive age with coincident or antecedent pregnancy. Primary extrauterine choriocarcinoma is rare and most reported cases have occurred in the uterine cervix.2 It is thought to arise along the path of migration of germ cells to gonads, or de-differentiated from another histological type.3 Our case was very unusual as it occurred in the vagina. The most common site of metastasis for choriocarcinoma is lung,1 and this also occurred in our patient.
 
The clinical diagnosis of extrauterine choriocarcinoma is extremely difficult as symptoms are often non-specific. Vaginal bleeding is the most common presenting symptom,2 but as such often mimics other more common disease entities. Primary extrauterine choriocarcinoma has been misdiagnosed as ectopic pregnancy,2 4 dysfunctional uterine haemorrhage,5 and cervical polyp.6 This can often lead to a delay in proper management. Since trophoblastic neoplasm such as choriocarcinoma produces an excessive amount of β-hCG, serial monitoring of its trend is very helpful for diagnosis and follow-up of treatment response. The mainstay of treatment is chemotherapy, as choriocarcinoma is highly chemosensitive.2 For a nulligravid woman as in this case, differentiation between gestational or non-gestational origin merely from a clinical history can be confusing. Differentiation by DNA polymorphism analysis is useful to guide the management as non-gestational choriocarcinoma is known to have a worse prognosis and to be resistant to single-agent chemotherapy.7
 
To the best of our knowledge, the imaging findings of primary extrauterine choriocarcinoma are rarely described in the literature, particularly that of vaginal origin. In the present case, MRI showed a hypointense vaginal tumour with hyperintense rim on T1-weighted images and heterogeneously hyperintense with hypointense rim on T2-weighted images. Rim enhancement was observed on T1-weight images after gadolinium contrast injection. The non-enhancing centre of the tumour could be due to tumour necrosis, commonly seen in choriocarcinoma. Poor delineation of fat planes with cervix and urinary bladder raised the suspicion of tumour involvement. Features of chronic bladder outlet obstruction were present as suggested by the trabeculated bladder outline. The signal void foci over the uterine wall and the high-flow vasculatures at the left adnexal region signified angiogenesis and neovascularisation, thus the hypervascular nature of the tumour.1 This is in accordance with the characteristic hypervascularity of choriocarcinoma.5 6 The multiple nodular opacities on chest X-ray most likely represented lung metastases, although histological confirmation was not performed. Interval shrinkage of these nodules was observed on chest X-ray following initiation of treatment.
 
In summary, imaging findings of a hypervascular tumour and exceedingly high levels of β-hCG are useful in making the diagnosis of extrauterine choriocarcinoma, and MRI is valuable in assessing extrauterine extension, tumour vascularity, and overall staging of the tumour.
 
References
1. Allen SD, Lim AK, Seckl MJ, Blunt DM, Mitchell AW. Radiology of gestational trophoblastic neoplasia. Clin Radiol 2006;61:301-13. Crossref
2. Kairi-Vassilatou E, Papakonstantinou K, Grapsa D, Kondi-Paphiti A, Hasiakos D. Primary gestational choriocarcinoma of the uterine cervix. Report of a case and review of the literature. Int J Gynecol Cancer 2007;17:921-5. Crossref
3. Dilek S, Pata O, Tok E, Polat A. Extraovarian nongestational choriocarcinoma in a postmenopausal woman. Int J Gynecol Cancer 2004;14:1033-5. Crossref
4. Gerson RF, Lee EY, Gorman E. Primary extrauterine ovarian choriocarcinoma mistaken for ectopic pregnancy: sonographic imaging findings. AJR Am J Roentgenol 2007;189:W280-3. Crossref
5. Maestá I, Michelin OC, Traiman P, Hokama P, Rudge MV. Primary non-gestational choriocarcinoma of the uterine cervix: a case report. Gynecol Oncol 2005;98:146-50. Crossref
6. Yahata T, Kodama S, Kase H, et al. Primary choriocarcinoma of the uterine cervix: clinical, MRI, and color Doppler ultrasonographic study. Gynecol Oncol 1997;64:274-8. Crossref
7. Koo HL, Choi J, Kim KR, Kim JH. Pure non-gestational choriocarcinoma of the ovary diagnosed by DNA polymorphism analysis. Pathol Int 2006;56:613-6. Crossref

Anti-neutrophil cytoplasmic antibody– associated pauci-immune glomerulonephritis in a patient with chronic lymphocytic leukaemia

Untitled Document
DOI: 10.12809/hkmj144421
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Anti-neutrophil cytoplasmic antibody–associated pauci-immune glomerulonephritis in a patient with chronic lymphocytic leukaemia
CS Yeung, MB, BS, MRCP1; CY Cheung, PhD, FHKAM (Medicine)1; PT Chan, MB, BS, FHKAM (Pathology)2; John W Li, MB, BS, MRCP1; WL Chak, FRCP, FHKAM (Medicine)1; KF Chau, FRCP, FHKAM (Medicine)1
1 Department of Medicine, Queen Elizabeth Hospital, Jordan, Hong Kong
2 Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong
 
Corresponding author: Dr CY Cheung (simoncycheung@gmail.com)
 
 Full paper in PDF
 
Case report
A 71-year-old woman presented to us in August 2012 with a rash over both lower limbs. Blood tests revealed leukocytosis with white cell count of 22 x 109 /L (neutrophil 1.6 x 109 /L, lymphocytes 20 x 109 /L). Serum creatinine level was 53 µmol/L and serum albumin 42 g/L. Urinalysis showed no albuminuria or microscopic haematuria. Bone marrow biopsy confirmed the diagnosis of chronic lymphocytic leukaemia (CLL). Fluorescence in-situ hybridisation showed deletion of chromosome 11q22~23. Computed tomography revealed multiple enlarged lymph nodes in different regions such as submental, bilateral jugular, left supraclavicular fossa, mediastinal, hila, axillary, porta hepatis, para-aortic and bilateral common iliac regions. Chlorambucil 2 mg twice weekly was prescribed and the patient was followed up regularly in our clinic. During this period she had two episodes of sepsis that were treated successfully with antibiotics.
 
In October 2013, she was noted to have progressive bilateral lower limb swelling and facial puffiness. She also reported frothy urine but no gross haematuria. She denied taking any herbs or over-the-counter medication. Physical examination was unremarkable except for pitting oedema over both lower limbs. Urinalysis revealed the presence of 10-50 red blood cells/cm2. The spot urine protein-to-creatinine ratio was 13.1 g/g. Her serum creatinine concentration was 364 µmol/L (reference range [RR], 65-100 µmol/L), albumin was 32 g/L (RR, 35-52 g/L), globulin was 40 g/L (RR, 22-36 g/L), haemogloblin was 87 g/L (RR, 134-171 g/L), and white blood cell count was 26.4 x 109 /L (RR, 3.7-9.2 x 109 /L) [neutrophil 3.9 x 109 /L, lymphocytes 22.1 x 109 /L]. The liver function was normal. Anti-nuclear antibody was positive (titre 1:80, homogeneous pattern) but anti-DNA was negative. Her anti-neutrophil cytoplasmic antibodies (ANCA) were positive with perinuclear staining pattern (pANCA) and the anti-myeloperoxidase (anti-MPO) antibody titre was >100 U/mL (reference level, <5 U/mL). The complement level was normal and hepatitis serology was negative. Urine culture showed no bacterial growth. Ultrasound-guided renal biopsy was performed. Light microscopic examination showed 21 glomeruli, three of which showed global glomerulosclerosis (Fig 1). Twelve glomeruli featured crescent formation (3 had cellular crescent, 6 had fibrocellular crescent, and 3 had fibrous crescent). Fibrinoid necrosis was also identified. Nonetheless, immunohistochemical staining showed several atypical lymphoid cell aggregates composed of small- to medium-sized lymphoid cells expressing B-cell markers CD20, CD5, CD23 and LEF-1 (Fig 2). They were negative for T-cell marker CD3, follicular centre marker CD10 and cyclin D1. The overall features supported the diagnosis of ANCA-associated crescentic glomerulonephritis and renal involvement of CLL. She was given 3 days of intravenous pulse methylprednisolone 500 mg, followed by daily oral prednisolone 30 mg and cyclophosphamide 50 mg. In addition, chlorambucil was stopped and monthly rituximab (first dose 375 mg/m2, subsequent doses 500 mg/m2) was administered. After 6 months, her lymphocyte count was normal and serum creatinine level was around 142 µmol/L. Proteinuria also reduced to 1.12 g/day and her last anti-MPO level was 11 U/mL.
 

Figure 1. One of the glomeruli shows rupture of glomerular basement membrane with fibrinoid necrosis under light microscopy (PASM stain; original magnification, x 400)
 

Figure 2. Immunohistochemical study shows presence of several atypical lymphoid cell aggregates composed of small- to mediumsized lymphoid cells expressing B-cell marker CD20 and CD5 with negative CD3 (immunostain with polymer/multimer DAB detection system on paraffin embedded sections; original magnification, x 100)
 
Discussion
We present a rare case of a 71-year-old woman with ANCA-associated crescentic glomerulonephritis that occurred simultaneously with renal infiltration of CLL. Such leukaemia is one of the chronic lymphoproliferative disorders characterised by a progressive accumulation of functionally incompetent lymphocytes that are monoclonal in origin. In fact, CLL can be considered to be identical to the mature (peripheral) B cell neoplasm small lymphocytic lymphoma (SLL) but at different stages along a continuum. Patients in an early stage of CLL are usually asymptomatic. The most common presentation is the incidental finding of leukocytosis, especially lymphocytosis. Other presenting signs and symptoms include malaise, weakness, anaemic symptoms, night sweating, recurrent infection, and lymphadenopathy. The diagnosis of CLL requires demonstration of lymphocytes with monoclonal B cells in either serum or bone marrow. Monoclonal B cells can be demonstrated by the expression of CD5 antigen.
 
The disease CLL/SLL is commonly associated with various glomerular disease entities such as minimal-change glomerulopathy, membranoproliferative glomerulonephritis, membranous glomerulopathy, focal segmental glomerulosclerosis, light-chain deposition disease, amyloidosis, and immunotactoid glomerulopathy.1 In addition, CLL can infiltrate various internal organs such as the kidneys. Previous studies have shown on autopsy that the kidneys were involved in 60% to 90% of CLL cases.2 3 Renal infiltration of CLL can be easily missed however, because it is usually asymptomatic and is not a common cause of acute kidney injury or end-stage renal disease.4 5 As a result, the interstitial inflammatory cell infiltrate in the renal biopsy specimen should be examined with immunofluorescence and electron microscopy.
 
Moreover, CLL can also be associated with autoimmune diseases, notably haematological diseases such as haemolytic anaemia, thrombocytopenia, and pure red cell aplasia.6 Approximately 2% of patients with CLL have associated pANCA positivity.7 Titre of ANCA has been shown to be involved in the pathogenesis of pauci-immune crescentic glomerulonephritis.8 Hence, it is not surprising that CLL can be associated with rapidly progressive glomerulonephritis (RPGN). The association between CLL/SLL and RPGN, however, has been shown in only a few case reports, and while renal histology was lacking in some of these patients, most of them were found to have positivity for pANCA and anti-MPO when serologic tests were available.1 9 10 11 12 13 14
 
There have been no large-scale randomised controlled trials for the treatment of CLL-related pauci-immune glomerulonephritis because of the limited number of patients. Most reported cases have been treated in the same way as other pauci-immune glomerulonephritis.9 Medication used in the treatment of RPGN such as steroid, cyclophosphamide, chlorambucil, and rituximab can also be used to treat CLL. In comparison, the combination chemotherapy for high-risk CLL—which includes fludarabine, cyclophosphamide, and rituximab—shows a higher complete response rate.15 It has been postulated that successful treatment of CLL will eventually result in resolution of RPGN.
 
In conclusion, we report a rare case of anti-MPO antibody–related crescentic glomerulonephritis in a patient with a known history of CLL. Awareness of this rare complication in patients with CLL with early screening, close follow-up of renal function, and timely appropriate treatment are important. Further trials may be required to determine definitive treatment when these diseases co-exist.
 
References
1. Moulin B, Ronco PM, Mougenot B, Francois A, Fillastre JP, Mignon F. Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas. Kidney Int 1992;42:127-35. Crossref
2. Barcos M, Lane W, Gomez G, et al. An autopsy study of 1206 acute and chronic leukemias (1958 to 1982). Cancer 1987;60:827-37. Crossref
3. Schwartz J, Shamsuddin A. The effects of leukemic infiltrates in various organs in chronic lymphocytic leukemia. Hum Pathol 1981;12:432-40. Crossref
4. Boudville N, Latham B, Cordingly F, Warr K. Renal failure in a patient with leukaemic infiltration of the kidney and polyomavirus infection. Nephrol Dial Transplant 2001;16:1059-61. Crossref
5. Hewamana S, Pepper C, Jenkins C, Rowntree C. Acute renal failure as the presenting feature of leukaemic infiltration in chronic lymphocytic leukaemia. Clin Exp Nephrol 2009;13:179-81. Crossref
6. Diehl LF, Ketchum LH. Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia. Semin Oncol 1998;25:80-97.
7. Cil T, Altintas A, Isikdogan A, Batun S. Prevalence of antineutrophil cytoplasmic antibody positivity in patients with Hodgkin’s and non-Hodgkin lymphoma: a single center experience. Int J Hematol 2009;9:52-7. Crossref
8. Xiao H, Heeringa P, Hu P, et al. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 2002;110:955-63. Crossref
9. Henriksen KJ, Hong RB, Sobrero MI, Chang A. Rare association of chronic lymphocytic leukemia/small lymphocytic lymphoma, ANCAs, and pauci-immune crescentic glomerulonephritis. Am J Kidney Dis 2011;57:170-4. Crossref
10. Biava CG, Gonwa TA, Naughton JL, Hopper J Jr. Crescentic glomerulonephritis associated with nonrenal malignancies. Am J Nephrol 1984;4:208-14. Crossref
11. Rivera M, González C, Gonzalo A, Quereda C, Fogué L, Ortuño J. Vasculitis associated with non-Hodgkin’s lymphoma. Nephron 1993;65:167-8. Crossref
12. Dussol B, Brunet P, Vacher-Coponat H, Bouabdallah R, Chetaille P, Berland Y. Crescentic glomerulonephritis with antineutrophil cytoplasmic antibodies associated with chronic lymphocytic leukaemia. Nephrol Dial Transplant 1997;12:785-6. Crossref
13. Tisler A, Pierratos A, Lipton JH. Crescentic glomerulonephritis associated with p-ANCA positivity in fludarabine-treated chronic lymphocytic leukaemia. Nephrol Dial Transplant 1996;11:2306-8. Crossref
14. Hamidou MA, El Kouri D, Audrain M, Grolleau JY. Systemic antineutrophil cytoplasmic antibody vasculitis associated with lymphoid neoplasia. Ann Rheum Dis 2001;60:293-5. Crossref
15. Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28:1756-65. Crossref

Trampoline-related injuries in Hong Kong

DOI: 10.12809/hkmj144411
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Trampoline-related injuries in Hong Kong
MY Cheung, MB, BS; CL Lai, MB, BS; Wilson HY Lam, MB, BS; James SK Lau, BSc, MB, BS; Aaron KH Lee, MB, ChB; Gabrielle G Yuen, MB, BS; YK Chan, FRCS, FHKAM (Orthopaedic Surgery); WL Tsang, FRCS, FHKAM (Orthopaedic Surgery)
Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
 
Corresponding author: Dr James SK Lau (jameslau@gmail.com)
 
 Full paper in PDF
 
Case reports
The following three cases highlight the potential serious consequences of trampolining.
 
Case 1: Lisfranc fracture
A 27-year-old woman with good past health was admitted with left foot pain and swelling in July 2014. She fell with axial loading on an inverted and plantar-flexed left foot while trampolining. Physical examination showed bruising on the dorsum of her left foot with tenderness over the base of the first and second metatarsals. Range of movement was limited by pain. Subsequent X-ray showed widening of the Lisfranc joint with base avulsion (Fig a). Lisfranc fracture was diagnosed. Open reduction with screw and K-wire fixation were performed and a resting ankle-foot orthosis was given. On follow-up 2 weeks after surgery, sensation and circulation in the toes were good. Range of movement was still limited by pain, however. She was encouraged to move her ankle and toes, and to mobilise with heel-walking at 6 weeks postoperatively.
 

Figure. Images of the case illustrations
(a) X-ray of the left foot (dorsoplantar view) of patient 1 showing widening of Lisfranc joint (arrow). (b) Computed tomography of the spine (reconstructed sagittal view) of patient 2 demonstrating two-column fractures of T12 and L1 (arrows). (c) X-ray of the left ankle (lateral view) of patient 3 illustrating posterior talus dislocation (arrow)
 
Case 2: vertebral fracture
A 25-year-old swimming instructor with good past health was admitted for thoracolumbar back pain after jumping and falling from 1 metre while trampolining in August 2014. He landed on his upper back with his body flexed on a trampoline. On examination, there was local tenderness at the thoracolumbar junction. His power and sensation across L2 to S1 were normal, reflexes were present, and anal sensation and tone were intact. Lumbosacral spine X-ray showed collapsed T12 and L1 with local kyphosis of 25°. Computed tomographic scan was performed subsequently, detailing a two-column fracture of T12 and L1 with anterior wedging of 20% (Fig b). He was put on a rigid thoracolumbar orthosis for 8 weeks and prescribed analgesics. Close monitoring for further collapse was warranted. During follow-up, he had no complaints of pain or neurological symptoms. Follow-up X-ray of the lumbosacral spine was static.
 
Case 3: ankle dislocation
A 22-year-old woman with good past health was admitted with left ankle pain and deformity after landing on a trampoline with plantar flexion and ankle inversion in August 2014. Physical examination revealed a deformed left ankle joint in medial rotation and plantar flexion. There was bruising over the left foot dorsum and marked tenderness over the whole ankle joint line. She could move her toes only slightly. Distal circulation was intact, but sensation was reduced over her left foot and toes. X-ray of the left ankle showed posterior talus dislocation without definite fracture (Fig c). Closed reduction was performed under sedation and a short leg slab was applied. Post-reduction X-ray showed a congruent ankle joint. Computed tomography showed no fracture. Magnetic resonance imaging of the left ankle showed small cortical fractures at the medial body of talus and posterior aspect of distal talus, complete tear of the calcaneofibular ligament and anterior talofibular ligament, and a partial thickness tear of the deep deltoid ligament. Immobilisation with a short leg cast is planned after oedema has subsided.
 
Discussion
In Hong Kong, trampolining was once a part of school physical education classes since it improves motor control and increases physical activity.1 However, following a trampoline incident in 1991 that resulted in quadriplegia,2 its popularity dwindled. Since the opening of the first trampoline park in Hong Kong in late July 2014,3 an increase in the number of trampoline-related injuries requiring admission to our department has been noted. Eight trampoline-related admissions were observed in less than 2 months. It has been estimated that the incidence of injuries that required admission to our unit was 1.9 per 10 000.4 The reasons of admission included Lisfranc fracture, vertebral fracture, ankle dislocation, anterior cruciate ligament tear of the knee, and neck and back sprains (Table). All patients were previously healthy but had no trampolining experience when they attended the indoor trampoline park for recreation and injured themselves while landing on a trampoline mat. Physicians and the general public need to be aware that trampolining can result in significant injuries, leading to acute hospital admission or even early surgical attention.
 

Table. Summary of cases admitted to Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital from 25 July to 6 September 2014
 
Literature review
In a New Zealand study, most trampoline injuries occurred on home trampolines.5 With its limited space, home trampolining is not popular in Hong Kong, thus there is a lack of local studies. Nonetheless since the recent opening of a trampoline park in our cluster, the awareness of trampoline-related injuries has risen rapidly. In less than 2 months, eight patients were admitted for trampoline-related injuries. Their age ranged from 22 to 48 years, with seven aged between 22 and 30 years. In overseas studies, the highest incidence of injury occurred in patients under 20 years of age.5 6 This is related to accessibility to home trampolines.
 
Nysted and Drogset1 evaluated a total of 551 injuries, among which 292 cases were secondary to awkward landing on the trampoline1 in comparison with seven out of eight cases observed locally. The second and third most common mechanism of injury was falling off the trampoline and collision with another person, respectively.1 Falling off the trampoline is not possible in our setting since there are multiple interconnected trampolines that are levelled with a padded ground. The fourth commonly reported injury was caused by performing a somersault (11%)1 on the trampoline which was the cause of injury in our eighth patient. In another study by Alexander et al,7 a similar trend is seen. A majority of injuries (42%) were due to landing badly on the trampoline. Injuries from the frame/springs, presence of multiple jumpers, and getting on/off constituted 19%, 10% and 2% of all trampoline injuries, respectively. In short, serious injuries can happen even when landing on a soft surface such as a trampoline mat where participants may be less cautious.
 
In our report, there was a lack of injuries involving the upper extremities, contrary to the findings of overseas studies. This could be skewed by the small sample size as well as the nature of trampolining; untrained adults tend to be more conservative and land axially on their feet. Hence the majority of our cases involved the lower extremities (50%), and is congruent with the findings of Hume et al5 and Nysted and Drogset1 (46% and 45%, respectively). Another important point to note is that injuries involving the spine are not uncommon (25%).
 
Regarding the types of injury, fractures constituted a significant proportion of injuries in the studies of Nysted and Drogset1 and Chalmers et al8 (36% and 68%, respectively), and was also the case in our study (37.5%). A small proportion of local injuries were dislocation, which is observed in the same studies.1 8
 
Safety measures
In addition to regular maintenance and a readily available first-aid kit, a number of measures can be taken that may lower the injury rates. Most importantly, participants should be verbally briefed by the facility provider about the risks and dangers of trampoline use.9 For example, only one participant should be on a trampoline mat at any given time.9 Black and Amadeo10 emphasised the importance of multiple jumpers as a risk factor for injuries due to the elastic recoil generated by a larger person jumping on the mat.
 
In order to familiarise participants with the elasticity of a trampoline, trampolines of lower elasticity should be provided for warm-up. This is a common practice in formal training,11 and may reduce the chance of awkward landing due to motor incoordination. Another suggestion is to restrict beginners from performing complex movements such as somersaults and flips.9 To achieve this, the provider may provide a separate area for advanced participants. It is important to note that padding to cover frames has not been shown to reduce injuries.7 Injury rates should be monitored8 closely by the provider so that the effectiveness of safety measures can be evaluated.
 
Limitations and suggestions
Injuries that did not require hospital admission were not included, such as those in patients who presented to general practitioners or who were discharged from the emergency department. Furthermore, this report can only include cases that occurred up to the time of writing. This may underestimate the problem and lead to inaccurate interpretation. It is also difficult to draw comparisons with epidemiological data from other countries where the majority of injuries arise from home trampoline use and not from trampoline parks. Lastly, although trampolining may be perceived as a dangerous physical activity, this may not be the case; the risk of injury is not high compared with other physical activities.
 
Acknowledgement
We thank Dr Siu-ho Wan for encouragement, guidance, and assistance throughout the preparation of the case reports.
 
References
1. Nysted M, Drogset JO. Trampoline injuries. Br J Sports Med 2006;40:984-7. Crossref
2. Tang SP. I want euthanasia [In Chinese]. Hong Kong: Joint Publishing (HK) Co Ltd; 2007.
3. South China Morning Post. Hong Kong’s first trampoline park, Ryze, is bound to be fun. Available from: http://yp.scmp.com/news/sports/article/90339/hong-kongs-first-trampoline-park-ryze-bound-be-fun. Accessed 4 Sep 2014.
4. South China Morning Post. Trampoline centre Ryze proves a summer hit with Hong Kong youth. Available from: http://www.scmp.com/news/hong-kong/article/1565201/trampoline-centre-ryze-proves-summer-hit-hong-kong-youth. Accessed 26 Feb 2014.
5. Hume PA, Chalmers DJ, Wilson BD. Trampoline injury in New Zealand: emergency care. Br J Sports Med 1996;30:327-30. Crossref
6. Hammer A, Schwartzbach AL, Paulev PE. Trampoline training injuries—one hundred and ninety-five cases. Br J Sports Med 1981;15:151-8. Crossref
7. Alexander K, Eager D, Scarrott C, Sushinsky G. Effectiveness of pads and enclosures as safety interventions on consumer trampolines. Inj Prev 2010;16:185-9. Crossref
8. Chalmers DJ, Hume PA, Wilson BD. Trampolines in New Zealand: a decade of injuries. Br J Sports Med 1994;28:234-8. Crossref
9. Council on Sports Medicine and Fitness, American Academy of Pediatrics, Briskin S, LaBotz M. Trampoline safety in childhood and adolescence. Pediatrics 2012;130:774-9. Crossref
10. Black BG, Amadeo R. Orthopedic injuries associated with backyard trampoline use in children. Can J Surg 2003;46:199-201.
11. USA Gymnastics. Basic trampoline—the beginning steps. Available from: https://usagym.org/pages/home/publications/technique/2000/3/basictrampoline.pdf. Accessed 8 Sep 2014.

Robotic left hepatectomy and Roux-en-Y right hepatico-jejunostomy for biliary papillomatosis

DOI: 10.12809/hkmj144324
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Robotic left hepatectomy and Roux-en-Y right hepatico-jejunostomy for biliary papillomatosis
Carmen CW Chu, MB, ChB, FRCSEd; Eric CH Lai, MB, ChB, FRACS; Oliver CY Chan, MB, ChB, FRCSEd; Daniel TM Chung, MB, ChB, FRCSEd; CN Tang, MB, BS, FRCSEd
Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
 
Corresponding author: Dr Eric CH Lai (ericlai@alumni.cuhk.edu.hk)
 
 Full paper in PDF
 
Click here to watch a video clip showing robot-assisted laparoscopic hemi-hepatectomy with biliary reconstruction
 
Case report
An 83-year-old male was referred to us for deranged liver function in December 2010. There was mildly elevated bilirubin level of 36 µmol/L, alkaline phosphatase level of 281 µmol/L, and transaminase level of 98 µmol/L. Tumour markers (carcinoembryonic antigen, alpha-fetoprotein, and carbohydrate antigen 19-9) were normal. Ultrasonography revealed a markedly dilated common bile duct (CBD) and intrahepatic ducts with irregular mural lesions.
 
Endoscopic retrograde cholangiopancreatography (ERCP) showed a grossly dilated CBD and intrahepatic ducts filled with thick mucus and multiple large filling defects. Brush cytology revealed atypical cells. A nasobiliary drainage catheter was inserted for biliary decompression. Bilateral percutaneous transhepatic biliary drainage (PTBD) catheters were later inserted due to inefficient nasobiliary drainage.
 
Further evaluation by computed tomographic scan showed dilatation of the whole biliary system with multiple papilloma-like lesions as shown in Figure 1. The presence of mucus in the biliary tree and image findings raised the suspicion of biliary papillomatosis. In order to localise and assess the extent of involvement, intra-operative choledochoscopy was performed via the PTBD tract. The PTBD tract was serially dilated up to 14 Fr to allow passage of a choledochoscope. Multiple biliary papillomas over the left hepatic duct, hilar bifurcation, and upper main bile duct were visualised. The right biliary system, lower CBD, and ampullary region were disease-free. After thorough assessment by intra-operative choledochoscopy, left hepatectomy and main bile duct excision with right hepatico-jejunostomy via robot-assisted laparoscopic approach was performed.
 

Figure 1. Computed tomography showing cystic dilatation of biliary tree with intramural components (arrow)
 
The patient was placed in the reverse Trendelenburg position with legs spread apart, and a 5- to 12-mm subumbilical port was inserted with the establishment of carbon dioxide pneumoperitoneum. After diagnostic laparoscopy, five trocars were inserted under direct vision. The extent of disease was assessed by intra-operative ultrasonography (BK Medical, Denmark). The da Vinci S Surgical System (Intuitive Surgical Inc, Sunnyvale [CA], US) was brought into position over the patient’s head and docked in. The assistant surgeon stayed on the right side of the patient and performed suction, stapling, and clipping through an assistant port over the right lower quadrant.
 
The intended extent of parenchymal resection was first marked on the liver surface with electrocautery. The main extrahepatic bile duct was dissected and slung with vascular tape. The right hepatic duct and lower CBD were transected and confirmed to have clear resection margins on frozen section. Porta dissection was performed. The left hepatic artery and left porta vein were dissected and transected. The main and right hepatic artery, and main and right portal vein were identified and protected. Left hemihepatectomy was performed with an ultrasonic surgical aspirator (SonoSurg, SS; Olympus Medical Systems Corporation, Tokyo, Japan) and coagulative scissors, under hemivascular inflow control. Large branches of vascular structures were controlled with endostaplers. A right hepatico-jejunostomy via Roux-en-Y reconstruction was fashioned with 3-0 poliglecaprone 25 (Monocryl, Ethicon; Johnson & Johnson, Amersfoort, The Netherlands) sutures intracorporeally. The side-to-side jejunojejunostomy was performed and the enterotomy site closed intracorporeally with an endostapler and 3-0 monocryl sutures. The specimen (Fig 2) was delivered via the extension of the left abdominal port. Operating time was 367 minutes and operative blood loss was 200 mL. The postoperative course was uneventful and the patient was discharged on postoperative day 13. Histopathological examination revealed extensive papillomatosis with villous adenomatous changes over both left hepatic ducts and the CBD associated with moderate-to-severe dysplasia. There was no evidence of invasion to suggest malignant transformation. At 50-month follow-up, the patient remained disease-free with no further biliary obstruction.
 

Figure 2. Resected specimen comprising gall bladder (G), left hemi liver (L), and common bile duct (B)
 
Discussion
Biliary papillomatosis is a rare condition characterised by papillary proliferation of the lining columnar epithelium of the bile ducts. It was first reported by Chappet1 in 1894 and was initially thought to be an entity with low malignant potential. Malignant transformation, however, is noted in 20% to 50% of cases as a consequence of adenoma carcinoma sequence.2 3
 
Middle-aged to elderly patients are commonly affected with a slight male predominance. The clinical presentation varies from being asymptomatic, as in our patient, to the presence of recurrent abdominal pain, obstructive jaundice, or recurrent cholangitis due to biliary obstruction by mucus.
 
The exact pathogenesis remains to be elucidated, but biliary papillomatosis is associated with conditions such as recurrent pyogenic cholangitis and congenital choledochal cyst. It has been postulated that longstanding irritation by stones or infection stimulates reactive hyperplasia with subsequent dysplasia in the biliary system.
 
Despite considerable improvements in imaging techniques, diagnosis remains a challenge as the presenting symptoms are more commonly caused by choledocholithiasis. Ultrasonography and computed tomography reveal intrabiliary masses with cystic dilatation in the proximal biliary tree. On the other hand, ERCP or magnetic resonance cholangiopancreatography shows an irregular filling defect that causes obstruction with proximal dilatation. The presence of mucobilia should raise the suspicion of biliary papillomatosis.
 
Histopathological examination reveals that the biliary system is often replaced by velvety papillary growth that possesses a fibrovascular core lined by columnar epithelium with varying degrees of cellular atypia.
 
Management is difficult due to the diffuse nature of the disease. A range of treatment strategies that include local ablation, photodynamic therapy, radical excision, or total hepatectomy with liver transplantation have been reported. Local ablative therapy and curettage, and radical excision with clear resection margins are associated with better survival.2 4
 
Accurate localisation and assessment of the extent of disease involvement remains pertinent to an accurate choice of treatment. In a Korean series by Lee et al,2 curative resection was associated with significantly better survival (60 months in curative resection vs 36 months in palliative surgery group); similar results were demonstrated by another series of 18 cases in China.5 Due to the high propensity for diffuse involvement, recurrence and malignant transformation, timely diagnosis and radical resection remain the cornerstone for successful treatment.
 
The advent of robotic surgery has brought about revolutionary changes in current surgical developments, but the feasibility and benefits in hepatobiliary surgeries are yet to be explored. Deep anatomical locations, complex vascularity, and large organ volume in hepatobiliary surgery often pose a challenge to the conventional laparoscopic approach. Such hurdles can be overcome by robotic surgery: recent studies have shown that a robot-assisted approach offers a safe and feasible option for hepatobiliary surgery with promising results.6 7 8 9 10 The enhanced dexterity of EndoWrist (Intuitive Surgical Inc, Sunnyvale [CA], US), with its 7 degrees of freedom of movement, allows meticulous dissection and precise tissue handling, enabling intracorporeal suturing even in the most technically demanding areas that would otherwise be impossible to access in conventional laparoscopic surgery. The three-dimensional stereoscopic video system with magnification enhances visualisation and depth perception. The third robotic arm also allows better organ retraction. The improving technical abilities of the robotic system for dissection and suturing extend the indications of minimally invasive liver surgery to liver resection requiring a biliary reconstruction. Without any doubt, the operation described in this case requires high technical skill and experience, and cannot be quickly introduced into routine practice. We performed this operation following accumulation of 10 years’ experience of conventional laparoscopic liver surgery and 2 years’ experience of robotic liver resection and robotic biliary surgery.8 9 10 11 12 Nonetheless, we believe that with the increasing popularity of robotic surgery, the required skill can be acquired with time. With the help of a robotic system, unilateral hepatico-jejunostomy reconstruction and porta structure dissection can be performed more easily than with the conventional laparoscopic technique.
 
In conclusion, the robotic approach to treatment of biliary papillomatosis is feasible and safe in selected patients. It also has the advantage of being minimally invasive.
 
References
1. Chappet V. Cancer epithelial primitif du canal cholédoque. Lyon Med 1894;76:145-57.
2. Lee SS, Kim MH, Lee SK, et al. Clinicopathologic review of 58 patients with biliary papillomatosis. Cancer 2004;100:783-93. Crossref
3. Wu SD, Lu CD, Lu CJ, Huang J, Zhou J. Mucin-producing intrahepatic biliary papillomatosis. Surg Today 2010;40:845-50. Crossref
4. Ludwig L, Büchler P, Kleeff J, et al. Multidisciplinary treatment of aggressive and rapidly progressing biliary papillomatosis. Dig Dis Sci 2010;55:3627-9. Crossref
5. Jiang L, Yan LN, Jiang LS, et al. Biliary papillomatosis: analysis of 18 cases. Chin Med J (Engl) 2008;121:2610-2.
6. Giulianotti PC, Sbrana F, Coratti A, et al. Totally robotic right hepatectomy: surgical technique and outcomes. Arch Surg 2011;146:844-50. Crossref
7. Choi GH, Choi SH, Kim SH, et al. Robotic liver resection: technique and results of 30 consecutive procedures. Surg Endosc 2012;26:2247-58. Crossref
8. Lai EC, Tang CN, Yang GP, Li MK. Multimodality laparoscopic liver resection for hepatic malignancy—from conventional total laparoscopic approach to robot-assisted laparoscopic approach. Int J Surg 2011;9:324-8. Crossref
9. Lai EC, Tang CN, Li MK. Robot-assisted laparoscopic hemi-hepatectomy: technique and surgical outcomes. Int J Surg 2012;10:11-5. Crossref
10. Lai EC, Yang GP, Tang CN. Robot-assisted laparoscopic liver resection for hepatocellular carcinoma: short-term outcome. Am J Surg 2013;205:697-702. Crossref
11. Lai EC, Tang CN, Ha JP, Li MK. Laparoscopic liver resection for hepatocellular carcinoma: ten-year experience in a single center. Arch Surg 2009;144:143-7; discussion 148. Crossref
12. Lai EC, Tang CN, Yang GP, Li MK. Minimally invasive surgical treatment of hepatocellular carcinoma: long-term outcome. World J Surg 2009;33:2150-4. Crossref

Extrapulmonary involvement associated with Mycoplasma pneumoniae infection

DOI: 10.12809/hkmj144403
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Extrapulmonary involvement associated with Mycoplasma pneumoniae infection
T Liong, FHKCP, FHKAM (Medicine)1; KL Lee, FHKCP, FHKAM (Medicine)1; YS Poon, FHKCP, FHKAM (Medicine)1; SY Lam, FHKCP, FHKAM (Medicine)1; KM Kwok, MRCP1; WF Ng, FHKAM (Pathology)2; TL Lam, FHKAM (Pathology)2; KI Law, FHKCP, FHKAM (Medicine)1
1 Intensive Care Unit, United Christian Hospital, Kwun Tong, Hong Kong
2 Department of Pathology, United Christian Hospital, Kwun Tong, Hong Kong
 
Corresponding author: Dr KI Law (lawki@ha.org.hk)
 
 Full paper in PDF
Abstract
Mycoplasma pneumoniae infection usually presents with upper and lower respiratory tract infection. Extrapulmonary involvement is not uncommon, however. We report two cases of predominantly extrapulmonary manifestations of Mycoplasma pneumoniae infection without significant pulmonary involvement. Both cases were diagnosed by serology. These cases illustrate the diversity of clinical presentations of Mycoplasma pneumoniae infection. Clinicians should maintain a high index of suspicion.
 
 
Case reports
Case 1
A 20-year-old man who worked as a car mechanic and enjoyed good health presented to United Christian Hospital in Hong Kong in August 2013 after collapsing suddenly at work. Ventricular arrhythmia was detected by ambulance men and defibrillation was performed 3 times with an automated external defibrillator. He was then transferred to the emergency department of the same hospital where he was observed to have persistent ventricular tachycardia and fibrillation. Advanced cardiac life support was continued, repeated defibrillation was performed and spontaneous circulation was restored 53 minutes later when he was then intubated.
 
Initial electrocardiogram after successful resuscitation showed diffuse ST elevation over the chest leads (Fig 1). Echocardiogram revealed poor left ventricular systolic function with global hypokinesia. Ad-hoc cardiac catheterisation was carried out. There was no coronary lesion and the patient was transferred to the intensive care unit (ICU) for therapeutic hypothermia.

Figure 1. Initial electrocardiogram of case 1
 
On arrival in ICU, the patient had a high fever up to 39.7°C. Blood pressure was normal on low-dose inotropes and pulse rate was 140 beats/minute. Glasgow Coma Scale score was 2 for eye opening, 1 for verbal response, and 1 for motor response. His pupils were equal and reactive, and bilateral plantar reflexes were equivocal. Frothy sputum was evident from the endotracheal tube but physical examination was otherwise unremarkable.
 
Initial blood tests revealed elevated white cell count (WCC) of 25.1 x 109 /L (reference range [RR], 3.9-9.3 x 109 /L), neutrophilia of 21.6 x 109 /L (RR, 1.8-6.2 x 109 /L), and normal lymphocyte count of 2.9 x 109 /L (RR, 1.0-3.2 x 109 /L). Haemoglobin level and platelet count were normal. He had mild renal and liver impairment with urea 8.2 mmol/L (RR, 2.8-8.1 mmol/L), and creatinine 138 µmol/L (RR, 62-106 µmol/L). Sodium and potassium levels were normal and alanine transferase (ALT) was 152 IU/L (reference level [RL], <41 IU/L). Creatinine kinase was 6439 IU/L (RR, 39-308 IU/L), and troponin I was 12 886 ng/L (RL, ≤14 ng/L). Initial urine toxic screening was negative. His first chest X-ray (CXR) showed right upper lobe consolidation, but repeated CXR the next morning showed almost complete resolution. Initial computed tomography (CT) of the brain was unremarkable.
 
Amoxicillin/clavulanate was started to cover aspiration pneumonia. Therapeutic hypothermia for neuroprotection and continuous veno-venous haemofiltration for acute kidney injury were commenced. On day 4 the patient developed convulsions and repeated CT brain showed diffuse cerebral oedema. An electroencephalogram showed diffuse encephalopathy compatible with severe hypoxic-ischaemic insult. The patient remained in a vegetative state and a tracheostomy was performed. He had repeated episodes of ventilator-associated pneumonia that were unresponsive to multiple regimens of antibiotics and finally succumbed on day 24 of admission.
 
Serology for viral studies was all negative. Nonetheless, paired serology for Mycoplasma pneumoniae on 26 August 2013 and 4 September 2013 showed a 4-fold decrease in antibody titres from 1:160 to 1:40, suggestive of recent M pneumoniae infection. Postmortem examination showed diffuse lymphocytic infiltrates and extensive myocardial necrosis within myocardial fibres (Fig 2). Reversetranscriptase polymerase chain reaction (RT-PCR) for M pneumoniae on bilateral lung tissue and myocardium were negative.

Figure 2. Case 1: (a) lymphocytic infiltrates within myocardial fibres (H&E; original magnification, x 200); (b) extensive myocardial necrosis (H&E; original magnification, x 400)
 
Case 2
A 57-year-old security guard with a history of infrequent asthma attacks but no regular follow-up attended the emergency department of United Christian Hospital in September 2013 with fever, chills, and rigors. He also complained of a new-onset maculopapular rash over the trunk and limbs that developed 1 day prior to admission. He volunteered that he was constantly exposed to insect bites due to the close proximity of rural areas to his working environment.
 
After admission to the medical ward, he developed a high fever of 40.3°C. Blood pressure was normal and pulse rate was 110 beats/minute. Oxygen saturation could be maintained on low-flow oxygen. Physical examination of the cardiovascular system, chest, and abdomen was normal but a maculopapular rash compatible with erythema multiforme over the back, lower abdomen, and bilateral lower limbs was observed. No eschar could be seen.
 
Initial investigations revealed the following: elevated WCC at 22.1 x 109 /L, neutrophilia of 21 x 109 /L, and lymphopenia of 0.2 x 109 /L. The haemoglobin level was 117 g/L (RR, 135-173 g/L) and platelet count was 79 x 109 /L (RR, 160-420 x 109 /L). The clotting profile was mildly deranged, with international normalised ratio of 1.3. He also had mild renal and liver impairment: creatinine 111 µmol/L, ALT 74 IU/L, and aspartate aminotransferase 101 IU/L. Initial CXR did not reveal any consolidative changes.
 
Amoxicillin/clavulanate was commenced but the patient’s condition deteriorated with development of septic shock that required high-dose inotropes, type I respiratory failure requiring high-flow oxygen, acute kidney injury, and disseminated intravascular coagulopathy despite change in antibiotic therapy to piperacillin/tazobactam and azithromycin soon after admission. He was transferred to ICU on day 3 of admission and required intubation due to aspiration. Antibiotics were changed to piperacillin/tazobactam and doxycycline. His condition gradually improved and he was successfully extubated and weaned off all inotropes. The skin rash also resolved spontaneously and repeated biochemistry tests revealed complete resolution of renal and liver derangement.
 
Skin biopsy was not performed. The Widal test and Weil-Felix tests were all negative. Paired serology of M pneumoniae showed a 4-fold rise in antibody titres from 1:<10 to 1:40, with confirmation of M pneumoniae infection. Viral serology for rubella and salmonella was not increased.
 
Discussion
We report two cases of M pneumoniae infection that presented with extrapulmonary symptoms and no significant respiratory involvement. Mycoplasma pneumoniae usually infects the upper and lower respiratory tract. Up to 50% of patients develop only mild upper respiratory tract symptoms such as cough, sore throat, malaise, and only 3% to 10% of patients develop pneumonia.1
 
Approximately 25% of patients infected with M pneumoniae develop extrapulmonary complications. This can happen before, during, or after the onset of or even in the absence of respiratory symptoms.1 An autoimmune reaction has been suggested as the pathogenesis of many of these extrapulmonary complications.1 The presence of organisms at an extrapulmonary site, however, suggests that direct invasion is also an important mechanism.2 3
 
The extrapulmonary manifestations associated with M pneumoniae may be neurological, cardiac, dermatological, musculoskeletal, haematological, and gastro-intestinal.4 Of these, neurological and dermatological symptoms are recognised as among the most common extrapulmonary manifestations of M pneumoniae infection.1 4
 
A wide range of dermatological manifestations has been described in patients with M pneumoniae infection. Mild symptoms include a maculopapular or vesicular rash.5 Erythema multiforme and Stevens-Johnson syndrome have a strong association with M pneumoniae infection.4 6 7 8
 
The patient in case 2 presented with sepsis and erythema multiforme. He was not prescribed any medication associated with erythema multiforme. Since a list of infective causes of erythema multiforme had been excluded by serology tests, his skin manifestation was most likely due to M pneumoniae infection.
 
Cardiac involvement is regarded as an uncommon complication of M pneumoniae infection.1 Pericarditis, myocarditis or pericardial effusion with or without tamponade effect have been described.1 It is more commonly found in adults than in paediatric patients.9 Fortunately, the outcome is generally good. Only a minority of patients had long-term sequelae and mortality is rare.10
 
Myocarditis associated with M pneumoniae infection that presents with ventricular arrhythmia as in case 1 is rare. We excluded other common causes of ventricular arrhythmia by initial blood tests, toxic screening, cardiac catheterisation, and CT brain. A 4-fold decrease in antibody titre of paired sera confirmed recent M pneumoniae infection. Autopsy results showed lymphocytic myocarditis. It is plausible, although not confirmative, that M pneumonia–associated myocarditis due to direct invasion of M pneumoniae cannot be shown by RT-PCR. Other differential diagnoses of lymphocytic myocarditis such as viral myocarditis were excluded by viral serology.
 
In addition to the diverse clinical manifestations, clinicians should also be aware of widespread macrolide resistance of M pneumoniae in Asia, including Hong Kong.11 High rates of macrolide resistance of up to 70% to 80% have been reported in China and Japan.12 13 14 Prompt adjustment of antibiotics to cover atypical pathogens is essential to successful treatment, as in our second patient. Consideration of alternatives such as doxycycline or fluoroquinolones as empirical treatment of atypical pathogens in areas with high rates of resistance may be appropriate.14
 
In conclusion, although M pneumoniae most commonly presents with respiratory tract symptoms, extrapulmonary manifestations are not uncommon. Clinicians should be aware of variable clinical presentations of M pneumoniae and macrolide resistance in our locality.
 
References
1. Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev 2004;17:697-728. Crossref
2. Kasahara I, Otsubo Y, Yanase T, Oshima H, Ichimaru H, Nakamura M. Isolation and characterization of Mycoplasma pneumoniae from cerebrospinal fluid of a patient with pneumonia and meningoencephalitis. J Infect Dis 1985;152:823-5. Crossref
3. Saïd MH, Layani MP, Colon S, Faraj G, Glastre C, Cochat P. Mycoplasma pneumoniae–associated nephritis in children. Pediatr Nephrol 1999;13:39-44. Crossref
4. Sánchez-Vargas FM, Gómez-Duarte OG. Mycoplasma pneumoniae—an emerging extra-pulmonary pathogen. Clin Microbiol Infect 2008;14:105-17. Crossref
5. Baum SG. Mycoplasma pneumoniae infection in adults. Available from: http://www.uptodate.com/contents/mycoplasma-pneumoniae-infection-in-adults? source=search_result&search=Mycoplasma+pneumoniae+infection+in+adults.&selectedTitle=1%7E116. Accessed Aug 2015.
6. Vanfleteren I, Van Gysel D, De Brandt C. Stevens-Johnson syndrome: a diagnostic challenge in the absence of skin lesions. Pediatr Dermatol 2003;20:52-6. Crossref
7. Vargas-Hitos JA, Manzano-Gamero MV, Jiménez-Alonso J. Erythema multiforme associated with Mycoplasma pneumoniae. Infection 2014;42:797-8. Crossref
8. Rock N, Belli D, Bajwa N. Erythema bullous multiforme: a complication of Mycoplasma pneumoniae infection. J Pediatr 2014;164:421. Crossref
9. Formosa GM, Bailey M, Barbara C, Muscat C, Grech V. Mycoplasma pneumonia—an unusual cause of acute myocarditis in childhood. Images Paediatr Cardiol 2006;8:7-10.
10. Paz A, Potasman I. Mycoplasma-associated carditis. Case reports and review. Cardiology 2002;97:83-8. Crossref
11. Ho PL, Wong SY, editors. Reducing bacterial resistance with IMPACT—Interhospital Multi-disciplinary Programme on Antimicrobial ChemoTherapy. 4th ed. Hong Kong SAR: Centre for Health Protection; 2012.
12. Yin YD, Cao B, Wang H, et al. Survey of macrolide resistance in Mycoplasma pneumoniae in adult patients with community-acquired pneumonia in Beijing, China [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi 2013;36:954-8.
13. Eshaghi A, Memari N, Tang P, et al. Macrolide-resistant Mycoplasma pneumoniae in humans, Ontario, Canada, 2010-2011. Emerg Infect Dis 2013;19(9). doi: 10.3201/eid1909.121466. Crossref
14. Okada T, Morozumi M, Tajima T, et al. Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children. Clin Infect Dis 2012;55:1642-9. Crossref

Churg-Strauss syndrome from an orthopaedic perspective

DOI: 10.12809/hkmj144357
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Churg-Strauss syndrome from an orthopaedic perspective
KL Kung, MB, BS; PK Yee, MB, ChB, FHKCOS
Department of Orthopaedics and Traumatology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong
 
Corresponding author: Dr KL Kung (lepetitcarmen@gmail.com)
 
 Full paper in PDF
Abstract
Churg-Strauss syndrome, which has been frequently described by physicians in the literature, is a small and medium-sized vessel systemic vasculitis typically associated with asthma, lung infiltrates, and hypereosinophilia. We report a case of Churg-Strauss syndrome with presenting symptoms of bilateral lower limb weakness and numbness only. The patient was admitted to an orthopaedic ward for management and a final diagnosis was reached following sural nerve biopsy. The patient’s symptoms responded promptly to steroid treatment and she was able to walk with a stick 3 weeks following admission. This report emphasises the need to be aware of this syndrome when managing patients with neurological deficit in order to achieve prompt diagnosis and treatment.
 
 
Introduction
Churg-Strauss syndrome (CSS) is a small and medium-sized vessel vasculitis that can affect different organs. The usual presentation is sub-optimised control of asthma together with involvement of other organs such as the heart, skin, and nervous system. It seldom presents with isolated neurological symptoms and has thus far not been reported from an orthopaedic aspect. We report a case of CSS in a patient who presented with neurological symptoms and who was admitted to the orthopaedic ward via casualty because of lower limb weakness and numbness.
 
Case report
A 66-year-old Chinese woman was admitted to the orthopaedic ward for 2 weeks in May 2013 because of weakness and numbness in both lower limbs. She had a more than 10 years’ history of asthma that was controlled with an inhaled bronchodilator and oral theophylline and terbutaline. The patient was prescribed an oral steroid intermittently for acute control. From January 2012 until the current admission, she had also been taking a leukotriene receptor antagonist (montelukast).
 
On admission, the patient complained of severe dysesthesia over both lower limbs, mainly below knee level. There was mild left proximal thigh pain. She had no low back pain and denied a history of recent trauma. The symptoms rendered the patient unable to walk.
 
Upon physical examination, she was afebrile, and cardiopulmonary and dermatological examination was unremarkable. Neurological examination revealed decreased sensation over both lower limbs in a glove and stocking distribution. Power of the muscles supplied by the peroneal and tibial nerves was grade 4 according to Medical Research Council grading system. Reflexes were diminished over both lower limbs. Per rectal examination revealed normal anal tone.
 
Blood tests revealed elevated white cell count to 28.07 x 109 /L with a predominance of eosinophils (20.46 x 109 /L). C-reactive protein was 65 mg/L. Erythrocyte sedimentation rate was 52 mm/h. Serum calcium, phosphate, alkaline phosphatase and creatine kinase level were normal. Sepsis workup including blood culture and urine culture were negative (Table).

Table. Summary of investigations
 
Radiography of the lumbar spine revealed grade-one spondylolisthesis at the lumbar 4 and 5 level. Radiography of the pelvis was unremarkable. Chest radiography showed slightly hyperinflated lung. Subsequent magnetic resonance imaging with contrast of the lumbar spine and pelvis was performed in view of the radiographic findings of the lumbar spine and the neurological deficit in the lower limbs. There was neither evidence of nerve root and cord compression nor infection around the lumbar spine.
 
Nerve conduction study showed absence of the compound muscle action potential (CMAP) of the right peroneal nerve recorded at the extensor digitorum brevis muscle. The CMAP was also decreased over bilateral tibialis anterior muscles. These results were suggestive of an axonal type of motor neuropathy over bilateral peroneal nerves and a sensory type of axonal neuropathy over the right lower limb. There was no involvement of the upper limbs.
 
Left sural nerve biopsy revealed epineurial extravascular eosinophils and vasculitis associated with axonal degeneration (Fig). There was one small epineurial artery infiltrated by eosinophils, polymorphs, and lymphocytes. Vague granuloma were present in the vascular wall. These features were consistent with CSS based on the American College of Rheumatology Classification criteria.1 The Table summarises the investigations.

Figure. Microscopy of sural nerve biopsy showing epineurial extravascular eosinophils and vasculitis associated with axonal degeneration; vague granuloma is formed in the vascular wall (arrow) [H&E; original magnification, x 100]
 
A rheumatologist was consulted who diagnosed CSS with peripheral neuropathy. Montelukast was discontinued in view of the possible association of the CSS. Oral prednisolone 40 mg daily was prescribed to the patient and an oral bisphosphonate was given to prevent osteoporosis. Distal lower limb power improved to grade 5 shortly following steroid treatment and there was marked improvement in pain and numbness. The eosinophil count and elevated inflammatory markers reduced rapidly over 6 days. The patient was discharged from the orthopaedic ward 2 weeks after treatment and was able to walk with a stick. The patient has been referred to a day hospital for further rehabilitation.
 
Discussion
Churg-Strauss syndrome is an entity frequently described by rheumatologists in the literature.2 It has seldom been reported by an orthopaedic surgeon. This case illustrates that common symptoms such as pain and numbness, frequently encountered when treating orthopaedic patients, may not be necessarily due to an orthopaedic problem. It may be a medical disease that requires prompt and specific treatment.
 
Allergic granulomatosis angiitis, or CSS, is a type of antineutrophil cytoplasmic antibody–associated small-vessel systemic vasculitis. Other diseases under the same group include microscopic polyangiitis and granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis.3 It was first described in 1951 by Dr Jacob Churg and Dr Lotte Strauss at Mount Sinai Hospital and is characterised by eosinophilic vasculitis that affects the small and medium-sized vessels. It describes the clinical symptoms of the pathological entity allergic angiitis and granulomatosis. The American College of Rheumatology has recommended that diagnosis of the syndrome is considered when four of the following features are present: (1) asthma, (2) eosinophils constituting more than 10% of the white cell count, (3) neuropathy, (4) non-fixed pulmonary infiltrates on radiography, (5) extravascular granulomas, and (6) abnormalities of the paranasal sinuses.1 The presence of four or more criteria yields a diagnostic sensitivity of 85% and a specificity of 99%.1
 
Despite variable clinical manifestations, pathological findings will include necrotising eosinophilic vasculitis that may result from endothelial cell adhesion and leukocyte activation, with subsequent necrotising vasculitis in several organ systems.
 
The pathogenesis of the syndrome is unclear, but it has been shown that HLA-DRB3 is a genetic risk factor for development. There have been reports about the strong association between CSS and the use of a leukotriene receptor antagonist (LTRA) such as montelukast. The mechanism by which LTRAs might cause eosinophilic vasculitis remains unclear, however. It is known that LTRAs do not inhibit leukotriene B4 (LTB4), which is a powerful chemoattractant for eosinophils. This could lead to increased plasma levels of LTB4 and trigger eosinophilic inflammation. Nevertheless, LTRA has a somewhat causative role in the development of CSS. A controlled study with a large number of patients is required to verify this conclusion.
 
The clinical presentation is variable. Some people have only mild symptoms, while others experience severe or life-threatening complications. There are three stages of CSS, but not every patient will develop all three phases or in the same order. They include:
(1) Allergic stage: the first stage of the syndrome in which the patient develops a number of allergic reactions including asthma, hay fever, and sinusitis.
(2) Eosinophilic stage: hypereosinophilia is found in the blood or tissue causing serious local damage. The lungs and digestive tract are most often involved. The symptoms may be relapsing and remitting and last for months or years.
(3) Vasculitic stage: the hallmark of this stage is blood vessel inflammation. The blood vessels are narrowed by inflammation and blood flow to tissue is jeopardised. During this phase, a feeling of general ill-health along with unintended weight loss, lymphadenopathy, weakness, and fatigue may occur.
 
Asthma is the central feature of CSS and precedes the systemic manifestations in almost all cases. Upper airway findings can include sinusitis, allergic rhinitis, and nasal polyps. Cardiac involvement represents the major cause of mortality. Granulomatous infiltration of the myocardium and coronary vessel vasculitis are the most common lesions. Congestive heart failure may develop rapidly and is often responsible for the mortality. Gastro-intestinal involvement such as abdominal pain, diarrhoea, and bleeding may also occur. Bowel perforation is the most severe manifestation and is one of the major causes of death. The glomerular lesion that typifies CSS is focal segmental glomerulonephritis with necrotising crescents. Its involvement is one of the poor prognostic factors. Arthralgias are frequent but arthritis with local inflammatory findings is rare, and joint deformity and radiographic erosions are usually not seen. Large articular joints are affected more than small joints. The symptoms usually regress quickly with treatment. Skin involvement occurs in 50% to 68% of patients and reflects the predilection for small vessels. Lesions are red or violaceous, and occur primarily on the scalp and the limbs or hands and feet. They are often bilateral and symmetrical.4
 
Peripheral neuropathy, as in our case, is common in patients with CSS (65-75%).5 6 The initial symptoms of neuropathy usually include an acute onset of tingling or painful paresthesia in the extremities. These symptoms predominantly occur in the distal portions of the extremities, particularly the lower limbs. In the initial phase, the distribution of sensory impairment usually takes the form of a mononeuritis multiplex pattern. As the disease progresses, it eventually evolves into a polyneuropathic pattern. Muscle weakness, to a variable extent and degree of asymmetry, may also be evident. There will be decreased or absent deep tendon reflexes corresponding to the distribution of nerves involved. Electromyography reveals axonal nerve involvement and often detects more extensive involvement than the clinical symptoms would indicate. With treatment, mononeuritis multiplex regresses progressively and patients may recover without sequelae. Prompt diagnosis and treatment are of paramount importance in managing CSS with neuropathy. If medical treatment is delayed, atrophy and weakness of the limbs may be irreversible and will require additional rehabilitation therapy including strengthening exercises, balance training, and ambulation training.
 
In the treatment of CSS, as with other forms of vasculitis, the symptoms respond to corticosteroids or other immunosuppressive drugs, eg cyclophosphamide and methotrexate.7 If refractory to these agents, intravenous immunoglobulin is the treatment of choice. Leukocytosis, eosinophilia, and raised erythrocyte sedimentation rates usually respond promptly after administration of these agents. Neuropathic pain also decreases rapidly in 85% of patients. There is speculation that the initial clinical course and the degree of systemic inflammatory involvement may influence long-term functional prognosis. Recent trials of treatment include immunomodulators such as rituximab, an anti-CD20 monoclonal antibody, and tumour necrosis factor–alpha.8
 
In this article, we have reviewed the clinical features, diagnostic criteria, and treatment options of CSS. In middle-aged or elderly patients, lower limb numbness and pain are frequently attributed to the degenerative spine with stenosis or nerve root compression. It is tempting to conclude that a patient has spinal stenosis or lumbar spondylosis in the presence of degenerative lumbar spine radiographs. This case highlights the need for clinicians to be vigilant for these manifestations in addition to the various diagnoses of spinal pathology when a patient presents with limb numbness and weakness together with a history of asthma and raised eosinophil count. Because signs and symptoms are both numerous and at times unassuming, it is notoriously difficult to diagnose CSS at the very initial phase. Nonetheless, significant neuropathic involvement may be prevented if a patient receives adequate therapy to induce remission of disease and prevent relapse. With treatment, most of the symptoms in any of the three phases can be relieved. We would like to raise the awareness of such an entity in treating patients with neuropathy. Close collaboration with rheumatologists in treating such a complex illness, including prompt diagnosis by performing nerve biopsy by an orthopaedic surgeon and prompt medical treatment by a rheumatologist, is the key to successful management.
 
References
1. Masi AT, Hunder GG, Lie TT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-100. Crossref
2. Churg J, Strauss L. Allergic granulomatosis, allergic rhinitis, and periarthritis nodosa. Am J Pathol 1951;27:277-301.
3. Falk RJ, Gross WL, Guillvein L, et al. Granulomatosis with polyangiitis (Wegener’s): An alternative name for Wegener’s granulomatosis. Arthritis Rheum 2011;63:863-4. Crossref
4. Guillevin L, Pagnoux C, Mouthon L. Churg-Strauss syndrome. Semin Respir Crit Care Med 2004;25:535-45. Crossref
5. Sehgal M, Swanson JW, DeRemee RA, Colby TV. Neurologic manifestations of Churg-Strauss syndrome. Mayo Clin Proc 1995;70:337-41. Crossref
6. Hattori N, Ichimura M, Nagamatsu M, et al. Clinicopathological features of Churg-Strauss syndrome–associated neuropathy. Brain 1999;122:427-39. Crossref
7. Bosch X, Guilabert A, Espinosa G, Mirapeix E. Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA 2007;298:655-69. Crossref
8. Thiel J, Hässler F, Salzer U, Voll RE, Venhoff N. Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Arthritis Res Ther 2013;15:R133. Crossref

Use of robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy in a paediatric patient: problem encountered

DOI: 10.12809/hkmj144340
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Use of robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy in a paediatric patient: problem encountered
Ivy HY Chan, FRCSEd(Paed), FHKAM (Surgery); Florence HQ Li, MB, ChB; Lawrence CL Lan, FRCSEd, FHKAM (Surgery); Kenneth KY Wong, FRCSEd, FHKAM (Surgery); Peter KF Yip, FRCSEd, FHKAM (Surgery); Paul KH Tam, FRCS (Edin, Glasg, Irel), FHKAM (Surgery)
Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong
Corresponding author: Dr Ivy HY Chan (ivyhychan@gmail.com)
 
 Full paper in PDF
 
Click here to watch a video clip showing robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy
 
Abstract
This report is of robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy in a 12-year-old patient with detrusor underactivity and hereditary sensory neuropathy. The whole operation was performed in 555 minutes with no open conversion. The patient experienced one episode of stomal stenosis, which required dilatation. At 3-year follow-up, the patient had both stomal and urinary continence. This is a safe and effective procedure to create a means of urinary catheterisation with avoidance of a large unsightly scar and comparable clinical outcome to an open procedure.
 
 
 
Introduction
The da Vinci Surgical System for robotic-assisted laparoscopic surgery was approved by the US Food and Drug Administration in 2000.1 Since its introduction, various types of operations have been successfully performed by robotic-assisted laparoscopic surgery. This technique, however, is limited by its lack of flexibility in the operative field and the size of paediatric patients. Therefore, its use is mainly confined in adult patients. Here, we describe the use of robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy in a paediatric patient with detrusor underactivity and sensory neuropathy.
 
Case report
In September 2009, a 12-year-old girl with hereditary sensory neuropathy presented to Queen Mary Hospital with overflow incontinence. She had a rare hereditary sensory neuropathy, which resulted in no pain sensation and no sensation of bladder fullness. As well as sensory neuropathy, she had mild mental retardation, and studied in a special school.
 
She presented with overflow incontinence, difficulty in initiating voiding, long voiding time, and large volume of post-void residual urine. The results of investigations—including renal function test, ultrasound of the urinary system, and magnetic resonance imaging of the lumbosacral spine—were normal. Video urodynamics revealed poor bladder sensation despite high detrusor pressure, low voiding detrusor pressure, and incomplete emptying. The overall impression was detrusor underactivity.
 
The initial treatment plan was for transurethral clean intermittent urinary catheterisation (CIC) to be performed regularly by the patient’s caregiver. Because of the patient’s mental status and uncooperability, however, she could not tolerate CIC. After thorough discussion, the patient’s parents agreed to the patient undergoing Mitrofanoff appendicovesicostomy.
 
The operation was performed in a Trendelenburg position. A 12-mm camera port was placed at the circumumbilical position. Two 8-mm working ports were placed one each at the left lower quadrant and right upper quadrant. A 5-mm assistant port was placed at the epigastric area, mainly for bowel retraction and passing sutures (Fig).
 

Figure. Position of the ports for the robotic-assisted laparoscopic Mitrofanoff procedure
‘12 mm’ denotes the camera port placed at the circumumbilical position, ‘8 mm’ denotes the two working ports placed at the left lower quadrant and right upper quadrant, and ‘5 mm’ denotes the assistant port placed at the epigastric area for bowel retraction and passing sutures
 
Preoperative intravenous antibiotics of amoxicillin-clavulanic acid 30 mg/kg were administered. A urinary catheter was inserted under aseptic conditions. The appendix was mobilised with its mesentery. However, the appendix and its mesentery appeared to be relatively short (appendix was approximately 6 cm and mesentery was approximately 4 cm) in this patient so the right colon was mobilised en bloc up to the hepatic flexure to create mobility of the appendix and its mesentery.
 
Initial mobilisation of the right colon and bladder was performed with conventional laparoscopy. The robotic system was docked in to perform the anastomosis between the bladder and appendix.
 
The urinary bladder was partially infused with normal saline via the urinary catheter. The tip of the appendix was opened and an 8-French infant feeding tube was inserted to ease manipulation of the appendix. The detrusor muscle was incised and opened by electrocautery at the supero-anterior aspect of the urinary bladder. Appendicovesicostomy was performed with 5/0 vicryl in an interrupted manner. The other end of the appendix was retrieved at the right lower quadrant of the abdominal wall. A V flap was created and the stoma was fashioned with 5/0 vicryl. The infant feeding tube was kept in situ as a stent. The whole operation took 555 minutes (9.25 hours).
 
The patient’s recovery was complicated by urinary tract infection with extended-spectrum beta-lactamase–producing Escherichia coli. Intravenous meropenem 20 mg/kg every 8 hours was initiated for 14 days. The infant feeding catheter was removed and the technique of CIC was taught to the patient’s caregiver.
 
The continence outcome was good as reported by the patient’s caregiver. There was no urine leak from the stoma or urethra. The technique of CIC with an 8-French catheter 4 times a day was performed uneventfully by the patient’s caregiver until around 6 months after the operation, when examination under anaesthesia and cystogram found mild stenosis of the stoma. Serial dilatation of the stoma site was suggested. There is no urine leak until the bladder reaches 400 mL in capacity. At 3-year follow-up, the patient’s caregiver can catheterise the bladder with ease and the patient has both stomal and urinary continence.
 
Discussion
The Mitrofanoff procedure was described in 1980.2 It uses the appendix to create a channel from the urinary bladder to the skin surface. This procedure has helped many patients who cannot tolerate urethral catheterisation over the past three decades. The procedure, however, was done via a conventional open surgery approach until 1993, when Jordan and Winslow3 described the technique of laparoscopic-assisted appendicovesicostomy. Despite the benefit of minimally invasive surgery, this technique has not become popular. In 2004, Pedraza et al4 and Hsu and Shortliffe5 described the use of the robotic-assisted technique in creating an appendicovesicostomy. Since then, a few case reports or case series6 7 8 have described this technique. This is largely attributed to the delicacy of the appendiceal blood supply and challenging intracorporeal anastomosis. The surgical robot offers three-dimensional visualisation, downscaling of surgeons’ tremor and hand movements, range of motion resembling that of the human wrist, and increased degrees of freedom.
 
The benefits of applying robotic technology for this procedure are greatest at two stages: first when dissecting the appendiceal blood supply and second when recreating a circumferential sealed anastomosis joining the appendix and bladder. Maintaining the blood supply to the appendix is one of the most important steps for avoiding cutaneous stomal stenosis and scarring. The challenge of making an intracorporeal watertight anastomosis may also be an important reason for the scarce reports of the pure laparoscopic approach for this technique. In view of this, there is no doubt that the surgical robot has a fine ability to mimic the open procedure without introducing a large unsightly abdominal incision.
 
On the other hand, the operative field is limited with the robotic system. This created a problem for this patient, as the appendix and its mesentery was short. The robotic machine was docked towards the feet of the patient and the targeted area of interest was at the pelvis and right lower quadrant. During mobilisation of the upper part of the right colon, crowding of instruments was encountered. As the port was placed as shown in the Figure, the operative field was fixed in the right lower quadrant. For mobilisation of the right colon, the operative field moved from the right lower quadrant to the right upper quadrant. The robotic instruments were not sufficiently flexible for the different surgical fields required for this patient, so we reverted to conventional laparoscopic mobilisation of the right colon. This necessitated more time to redock the whole system back to perform the appendicovesicostomy anastomosis. This is one of the drawbacks of the robotic-assisted Mitrofanoff procedure.
 
The short-term and mid-term outcomes of this patient are good. She recovered well and became fully mobilised on day 3 after operation. The continence outcome of this patient is good, and the caregiver also found this helpful for doing CIC for this patient.
 
Conclusion
The robotic-assisted laparoscopic Mitrofanoff procedure is a feasible and safe operation. The technique has the advantage of performing the delicate anastomosis between the appendix and the bladder intracorporeally. Lack of flexibility when changing the surgical field is the major drawback. The robotic-assisted laparoscopic Mitrofanoff procedure can produce a smaller scar and better cosmetic outcome.
 
References
1. Meadows M. Computer-assisted surgery: an update. Available from: http://web.archive.org/web/20090301135726/http://www.fda.gov/fdac/features/2005/405_computer.html. Accessed 9 Jul 2015.
2. Mitrofanoff P. Trans-appendicular continent cystostomy in the management of the neurogenic bladder [in French]. Chir Pediatr 1980;21:297-305.
3. Jordan GH, Winslow BH. Laparoscopically assisted continent catheterizable cutaneous appendicovesicostomy. J Endourol 1993;7:517-20. Crossref
4. Pedraza R, Weiser A, Franco I. Laparoscopic appendicovesicostomy (Mitrofanoff procedure) in a child using the da Vinci robotic system. J Urol 2004;171:1652-3. Crossref
5. Hsu TH, Shortliffe LD. Laparoscopic Mitrofanoff appendicovesicostomy. Urology 2004;64:802-4. Crossref
6. Storm DW, Fulmer BR, Sumfest JM. Laparoscopic robot-assisted appendicovesicostomy: an initial experience. J Endourol 2007;21:1015-8. Crossref
7. Thakre AA, Yeung CK, Peters C. Robot-assisted Mitrofanoff and Malone antegrade continence enema reconstruction using divided appendix. J Endourol 2008;22:2393-6. Crossref
8. Willie MA, Zagaja GP, Shalhav AL, Gundeti MS. Continence outcomes in patients undergoing robotic assisted laparoscopic mitrofanoff appendicovesicostomy. J Urol 2011;185:1438-43. Crossref

A lucky and reversible cause of 'ischaemic bowel'

DOI: 10.12809/hkmj144306
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
A lucky and reversible cause of ‘ischaemic bowel’
YF Shea, MRCP, FHKAM (Medicine)1; Felix CL Chow, MB, BS, MRCS2; F Chan, MRCP, FHKAM (Medicine)1; Janice JK Ip, MB, BS, FRCR3; Patrick KC Chiu, FRCP(Glasg), FHKAM (Medicine)1; Fion SY Chan, FRCS, FHKAM (Surgery)2; LW Chu, MD, FRCP1
1 Acute Geriatric Unit, Grantham Hospital, Aberdeen, Hong Kong
2 Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong
3 Department of Radiology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong
Corresponding author: Dr YF Shea (elphashea@gmail.com)
 
 Full paper in PDF
 
Abstract
An 81-year-old man was admitted with an infective exacerbation of chronic obstructive pulmonary disease. He also had clinical and radiological features suggestive of ileus. On day 6 after admission, he developed generalised abdominal pain. Urgent computed tomography of the abdomen showed presence of portovenous gas and dilated small bowel with pneumatosis intestinalis and whirl sign. Emergency laparotomy was performed, which showed a 7-mm perforated ulcer over the first part of the duodenum and small bowel volvulus. Omental patch repair and reduction of small bowel volvulus were performed. No bowel resection was required. The patient had a favourable outcome. Clinicians should suspect small bowel volvulus as a cause of ischaemic bowel. Presence of portovenous gas and pneumatosis intestinalis are normally considered to be signs of frank ischaemic bowel. The absence of bowel ischaemia at laparotomy in this patient shows that this is not necessarily the case and prompt surgical treatment could potentially save the bowels and lives of these patients.
 
 
Introduction
Ischaemic bowel is often associated with high mortality. Common causes of ischaemic bowel include atrial fibrillation with arterial embolism, incarcerated hernia, volvulus, profound shock, and vasculitis. Volvulus in adults most often occurs in the colon and sigmoid colon (70-80%), and less commonly in caecum (10-20%).1 Small bowel volvulus (SBV) is rarely encountered in adults.1 2 3 4 5 6 7 8 9 Intra-operatively, if gangrenous small bowel is found, it needs to be resected and may potentially cause long-term complications, including short bowel syndrome.2 We report on a patient with primary SBV associated with a perforated duodenal ulcer (PDU), but the patient had a favourable outcome without the need for bowel resection, thereby avoiding the long-term complications associated with extensive bowel resection.
 
Case report
In February 2014, an 81-year-old man was admitted with an infective exacerbation of chronic obstructive pulmonary disease caused by influenza B virus. He had a history of left inguinal hernia repair. On admission, he had a temperature of 38°C. He was tachypnoeic with diffuse expiratory wheeze on chest auscultation. His abdomen was slightly distended and bowel sounds were sluggish. There was no recurrence of the hernia. Complete blood count showed leukocytosis (23.7 x 109 /L [reference range, 4.5-11.0 x 109 /L]) and a haemoglobin level of 109 g/L (reference range, 140-175 g/L). Liver and renal function tests and electrolytes were normal. Chest radiograph showed hyperinflation of the lungs with no consolidation. Abdominal radiograph showed dilated small bowel without air-fluid level.
 
The patient was treated with inhaled bronchodilators (albuterol 4 puffs every 4 hours and ipratropium bromide 2 puffs every 4 hours) and intravenous amoxicillin-clavulanate 1.2 g every 8 hours for 6 days. The dilated small bowel was initially attributed to ileus and the patient was kept nil-by-mouth. Daily abdominal radiograph did not reveal any worsening of the small bowel dilatation. He developed an episode of fast atrial fibrillation on day 2, which was controlled with amiodarone (initially with intravenous loading and infusion, then followed by 200 mg orally twice a day). Flatus and bowel opening returned on day 5 and diet was resumed. On day 6, the patient developed generalised abdominal pain. His abdomen was distended with no localised tenderness, but bowel sounds were absent. Arterial blood gas showed no metabolic acidosis. Computed tomography (CT) of the abdomen with contrast showed presence of portovenous gas, dilated small bowel with pneumatosis intestinalis, and whirl sign (Fig 1).
 

Figure 1. Computed tomography images of the abdomen with contrast on day 6
(a) Axial view showing portovenous gas in the hepatic parenchyma (arrows) and ascites (asterisk); and (b) coronal view showing the whirl sign (white arrow) with mesentery appearing as a whirl-like pattern twisting around the axis of the superior mesenteric artery with small bowel dilatation (asterisk), pneumatosis intestinalis (black arrow), bowel wall oedema (white arrowheads) and impairment in bowel wall enhancement
 
Emergency laparotomy was performed that showed a 7-mm perforated ulcer over the first part of the duodenum, which was sealed off by the adjacent liver and falciform ligament. The small bowel was grossly distended. There was SBV with twisting of the small bowel along the root of the mesentery by 180° with mild dusky appearance. Omental patch repair of the duodenal ulcer and reduction of the SBV were performed. Small bowel perfusion improved significantly and a strong superior mesenteric artery pulse was confirmed. Bowel resection was not required. Histological examination of the duodenal ulcer showed no evidence of Helicobacter pylori infection. Repeated CT of the abdomen on day 8 showed resolution of portovenous gas (Fig 2). Postoperatively, the patient had the complication of an intra-abdominal abscess, which was managed successfully by percutaneous drainage and systemic antibiotics (vancomycin 500 mg daily and meropenem 1 g every 12 hours intravenously for 2 weeks followed by levofloxacin 500 mg orally daily for 1 week). He was discharged on day 36.
 

Figure 2. Computed tomography images of the abdomen with contrast 8 days after operation
(a) Axial view showing resolution of portovenous gas in the hepatic parenchyma and postoperative pneumoperitoneum (asterisk); (b) axial view showing resolution of the whirl sign and small bowel obstruction; and (c) coronal view showing untwisted mesentery
 
Discussion
The initial clinical feature of dilated small bowel with sluggish bowel sound in the background of an infective exacerbation of chronic obstructive pulmonary disease was interpreted as being caused by paralytic ileus.10 With the sudden worsening in abdominal pain and the presence of paroxysmal atrial fibrillation, the possibility of ischaemic bowel was reconsidered. This explains why SBV was only diagnosed by CT of the abdomen on day 6 after admission. Small bowel volvulus refers to the twisting of a small bowel segment around the axis of its own mesentery. In the elderly patients, a secondary type with an underlying cause is most commonly encountered.3 These secondary causes include tumours, mesenteric lymph nodes, adhesions after previous surgery, malrotation, congenital bands, intussusception, colostomy, and internal hernias.3 If no underlying cause is found, as in this patient, the SBV is considered to be a primary SBV (some surgeons may regard malrotation and congenital adhesions as primary SBV).3 4 There are certain risk factors that have been linked to primary SBV, including long mobile mesentery, short mesenteric base, long small bowel, and consumption of a large amount of fibre-rich food after prolonged fasting, with overloading of an empty intestine.1 3 6 With torsion of the small bowel and its mesentery, the superior mesenteric arterial blood supply is compromised, which results in bowel infarction that usually occurs within 6 hours.3
 
The most important clinical feature is persistent abdominal pain with absence of bowel sounds on physical examination.1 2 3 4 5 6 7 8 9 Plain abdominal radiography is of limited diagnostic value.4 Abdominal CT is the most useful tool for obtaining the correct preoperative diagnosis.4 The findings on CT of the abdomen reflect the underlying pathophysiology of the SBV. Whirl sign, which refers to the twisting of mesentery around the origin of the torsion, is the most typical radiological sign of SBV.4 7 8 9 Alternatively, a venous cut-off sign, referring to the occlusion of the superior mesenteric vein, may also be found.9 With lymphatic and venous occlusions, there will be small bowel wall oedema and thickening.4 Small bowel dilatation is caused by intestinal obstruction resulting from the torsion.4 The bowel wall ischaemia results from the pneumatosis intestinalis and portovenous gas.4 It has been proposed that with intestinal ischaemia, the gas produced by gas-forming organisms accumulates in the bowel wall (pneumatosis intestinalis) and circulates to the liver (portovenous gas); alternatively the gas-producing organisms may enter the portal circulation and produce the gas there (portovenous gas).11
 
The causal relationship between SBV and PDU in this patient is not well established. We suspected that both the SBV and a non-PDU might be present during the early phase of admission. The resumption of a meal after a period of fasting exacerbated the volvulus. It has been proposed that the transit of food contents into the empty proximal jejunum could cause a gravitational migration of this segment into the left lower quadrant; forcing the distal empty bowel loops in a clockwise direction to the right upper quadrant with torsion of the mesentery.6 The mechanical obstruction contributes to the perforation of the duodenal ulcer which was a weak point and, together with the impending bowel ischaemia, led to the generalised abdominal pain. The possibility of ileus converting into SBV was less likely because of the usually reversible nature of ileus with treatment of the infection.
 
A favourable outcome for patients with SBV depends on prompt emergency laparotomy.1 2 3 4 5 6 7 8 9 The absence of bowel gangrene intra-operatively predicted a favourable outcome for this patient. Strictly, volvulus is defined by more than 180° of rotation, so the intra-operative finding of small bowel twisting around the mesentery root by 180° may signify that the SBV was in the process of partially reversing by itself. In one case series involving 19 patients, Ruiz-Tovar et al6 noted 100% mortality in patients with an intra-operative finding of bowel wall gangrene. Birnbaum et al3 also reported the use of enteropexy to prevent recurrence of primary SBV in a 69-year-old man with long mobile mesentery.
 
In summary, clinicians should suspect SBV as a cause of ischaemic bowel. Presence of portovenous gas and pneumatosis intestinalis are normally considered signs of frank ischaemic bowel. The absence of bowel infarction in this patient illustrates that this is not necessarily the case and prompt surgical treatment could potentially save the bowels and lives of these patients.
 
References
1. Kim KH, Kim MC, Kim SH, Park KJ, Jung GJ. Laparoscopic management of a primary small bowel volvulus: a case report. Surg Laparosc Endosc Percutan Tech 2007;17:335-8. Crossref
2. Rubio PA, Galloway RE. Complete jejunoileal necrosis due to torsion of the superior mesenteric artery. South Med J 1990;83:1482-3. Crossref
3. Birnbaum DJ, Grègoire E, Campan P, Hardwigsen J, Le Treut YP. Primary small bowel volvulus in adult. J Emerg Med 2013;44:e329-30. Crossref
4. Jaramillo D, Raval B. CT diagnosis of primary small-bowel volvulus. AJR Am J Roentgenol 1986;147:941-2. Crossref
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7. Li CH, Chen CH, Chou JW. Intestinal obstruction caused by small bowel volvulus. Am J Med 2011;124:e3-4. Crossref
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Clozapine-induced acute interstitial nephritis

DOI: 10.12809/hkmj144312
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Clozapine-induced acute interstitial nephritis
SY Chan, MRCP (UK), FHKCP1; CY Cheung, PhD, FHKCP1; PT Chan, MB, BS, FHKCPath2; KF Chau, FHKCP, FRCP (Lond)1
1 Department of Medicine, Queen Elizabeth Hospital, Jordan, Hong Kong
2 Department of Pathology, Queen Elizabeth Hospital, Jordan, Hong Kong
Corresponding author: Dr SY Chan (helenchansy@gmail.com)
 
 Full paper in PDF
 
Abstract
Acute interstitial nephritis is a common cause of acute kidney injury. Acute interstitial nephritis is most commonly induced by drug although the cause may also be infective, autoimmune, or idiopathic. Although eosinophilia and eosinophiluria may help identify this disease entity, the gold standard for diagnosis remains renal biopsy. Prompt diagnosis is important because discontinuation of the culprit drugs can reduce further kidney injury. We present a patient with an underlying psychiatric disorder who was subsequently diagnosed with clozapine-induced acute interstitial nephritis. Monitoring of renal function during clozapine therapy is recommended for early recognition of this rare side-effect.
 
 
 
Case report
A 29-year-old woman with a known history of bipolar affective disorder and paranoid schizophrenia admitted to our hospital because of relapse of psychiatric symptoms in June 2011. She had no significant medical illness. Her medication included quetiapine fumarate and sodium valproate but was changed to haloperidol decanoate depot injection, trihexyphenidyl, and clozapine following hospitalisation. Clozapine was commenced at 50 mg once per day and gradually stepped up to 400 mg once per day. One week later she developed fever but had no respiratory or urinary symptoms. She remained conscious and alert with stable vital signs. Physical examination revealed no significant abnormality and preliminary investigations showed normochromic and normocytic anaemia with haemoglobin level of 87 g/L, white cell count of 11.8 x 109 /L (eosinophils 15.1%; absolute count 2.3 x 109 /L), and serum creatinine of 229 µmol/L (baseline serum creatinine 1 week ago, 39 µmol/L). Her liver enzymes, lactate dehydrogenase, and haptoglobin were all within normal range. Chest radiograph showed clear lung fields. She was empirically given amoxicillin/clavulanic acid but treatment was complicated by gastro-intestinal side-effects such as vomiting and diarrhoea. The antibiotics were stopped immediately and the symptoms subsided. Clozapine was further titrated up to 700 mg once per day with consequent improvement in her mental state. Nonetheless, fever persisted with further deterioration in renal function (serum creatinine rose to 356 µmol/L). Autoimmune markers including anti–nuclear antibody, anti–neutrophil cytoplasmic antibodies, and anti–glomerular basement membrane antibody were all within normal range. Urinalysis revealed the presence of red blood cells and eosinophils but urine culture showed no bacterial growth. The 24-hour urine protein was 1.18 g. Ultrasound of the urinary system showed normal-sized kidneys with no hydronephrosis. Ultrasound-guided renal biopsy was performed and the histology showed features of tubulointerstitial nephritis with eosinophil-rich interstitial infiltrates and occasional granulomas (Fig). The likely diagnosis was drug-induced acute interstitial nephritis (AIN). Clozapine was withheld, fever subsided afterwards and renal function gradually returned to normal 4 weeks following cessation of clozapine.
 

Figure. Histology of renal tissue showing eosinophil-rich interstitial infiltrates and occasional granulomas (arrows) [H&E; original magnification, x 200]
 
Discussion
Drug-induced AIN is not uncommon. Common nephrotoxic drugs include non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics such as aminoglycosides and vancomycin. Although amoxicillin/clavulanic acid remains a possible culprit in this case for AIN, the short duration of amoxicillin/clavulanic acid use and sequence of events are more suggestive of clozapine-induced AIN.
 
Acute interstitial nephritis is defined as an immune-mediated condition characterised by the presence of inflammation and oedema in the tubulointerstitium of the kidneys. It accounts for 15% to 27% of biopsy-proven acute kidney injury. Acute interstitial nephritis is most commonly drug-induced although the cause may also be infective, autoimmune, or idiopathic.1 2 3 4 5 The classic triad—fever, skin rash, and eosinophilia—is only present in 5% to 10% of patients with AIN.2 3 4 5 As a result, a high level of clinical suspicion is essential since around 40% of patients with AIN eventually required dialysis.2 A detailed drug history, especially herbal medicine which is common in our locality, recreational drugs and radio-contrast, are important for diagnosis. Other history including water exposure and animal contact (pets or stray animals) can help exclude or confirm several infective causes such as Legionnaires’ disease and leptospirosis. Systemic manifestations of vasculitis should also be specifically looked for during physical examination.
 
There are no specific signs and symptoms to differentiate drug-induced AIN from other causes of AIN. Fever is present in around 30% of patients with drug-induced AIN3 5 and it typically occurs within 2 weeks of initiation of a new drug.3 Skin rash, usually of morbilliform or maculopapular appearance, is found in only 15% to 50% of patients, depending on the type of medication.3 5 One retrospective review showed that around 45% of patients have arthralgia, and 15% and 21% of patients have dysuria and loin pain, respectively.5 Eosinophilia is thought to have great diagnostic value in drug-induced AIN as it signifies a hypersensitivity reaction although the degree and frequency of eosinophilia vary with different medications.4 Methicillin-induced AIN is associated with eosinophilia in 80% of cases while AIN due to NSAID is less commonly associated with eosinophilia, which is only around 35% of cases.4 However, the presence of eosinophilia can also be found in infections, especially those caused by helminths, allergic diseases such as asthma and eczema, and even malignant conditions such as lymphoma and carcinoma of the colon. Like eosinophilia, the presence of eosinophiluria is neither sensitive nor specific for drug-induced AIN. The sensitivity ranges from 63% to 91%, and specificity from 52% to 94%.3 4 Other conditions such as lower urinary tract infection, pyelonephritis, prostatitis, acute tubular necrosis, glomerulonephritis, and urinary schistosomiasis can also result in eosinophiluria.3 Other parameters from urine samples may also provide clues for drug-induced AIN. Proteinuria is present in 93% of patients but only 2.5% have a nephrotic range of proteinuria.2 Haematuria is usually microscopic and is present in 60% to 80% of cases while gross haematuria is only present in 5% of patients.2 Renal biopsy can confirm the diagnosis of AIN by demonstrating inflammation and oedema of the renal interstitium and tubulitis.2 3 4 5 The presence of a considerable number of eosinophils in the interstitium will point to a diagnosis of drug-induced AIN, while an abundance of neutrophils is suggestive of an infective cause.3
 
As drug-induced AIN is idiosyncratic and not dose-dependent, the mainstay of treatment is cessation of the causative agents. Nonetheless, not all patients experience complete recovery despite withdrawal of the index medication. Neither the severity of renal failure, the extent of interstitial involvement (including fibrosis), nor the severity of tubulitis predicts the clinical outcome.2 3 4 5 More established prognostic factors are the duration of renal failure and creatinine level 6 to 8 weeks after diagnosis.4 Some studies advocate the use of corticosteroid to hasten recovery and prevent progression to chronic kidney disease6 but these studies have usually been small and retrospective.2 3 4
 
Since 1999, 10 cases of clozapine-induced AIN have been described.6 7 8 Among these patients, the ages ranged from 24 to 69 years, and six were male. In patients who presented within 2 weeks of commencing clozapine, 80% exhibited a hypersensitivity reaction. In those who presented late, symptoms developed up to 3 months after starting clozapine. Fever was present in 80% but, surprisingly, none reported skin rash or arthralgia. Proteinuria was detected in 80% of cases, but only four patients had red blood cells in the urine. Eosinophilia was present in half of the patients only. Four patients had the diagnosis of AIN confirmed by histology. A phenomenon is observed wherein the effect of clozapine on the kidney can be potentiated by the concomitant use of antibiotics, especially those that are known to have higher risks of interstitial damage, such as the penicillin derivatives.6 In our patient, the temporal relationship between the initiation of clozapine and the development of acute kidney injury matched the time frame described in the literature. In addition, the presence of fever, eosinophilia, and eosinophiluria also raised the possibility of clozapine-induced AIN, subsequently confirmed by histology. The renal function of our patient also improved spontaneously after removing the index medication.
 
In conclusion, this case highlights the rare but important potential side-effect of clozapine. In addition to monitoring cell counts, regular monitoring of renal function is recommended after initiation of clozapine. Early involvement of nephrologists can provide early recognition of this entity with prompt investigation and treatment.
 
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