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.

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.

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

Click here to watch a video clip showing robot-assisted laparoscopic hemi-hepatectomy with biliary reconstruction

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.

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.

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.

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

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.

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).

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.

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.

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.

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

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.

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).

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.

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.

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

5. Weledji EP, Theophile N. Primary small bowel volvulus in adults can be fatal: a report of two cases and brief review of the subject. Trop Doct 2013;43:75-6. Crossref

6. Ruiz-Tovar J, Morales V, Sanjuanbenito A, Lobo E, Martinez-Molina E. Volvulus of the small bowel in adults. Am Surg 2009;75:1179-82.

7. Li CH, Chen CH, Chou JW. Intestinal obstruction caused by small bowel volvulus. Am J Med 2011;124:e3-4. Crossref

8. Huang YM, Wu CC. Whirl sign in small bowel volvulus. BMJ Case Rep 2012;2012:bcr2012006688.

9. Ho YC. “Venous cut-off sign” as an adjunct to the “whirl sign” in recognizing acute small bowel volvulus via CT scan. J Gastrointest Surg 2012;16:2005-6. Crossref

10. Batke M, Cappell MS. Adynamic ileus and acute colonic pseudo-obstruction. Med Clin North Am 2008;92:649-70,ix. Crossref

11. Abboud B, El Hachem J, Yazbeck T, Doumit C. Hepatic portal venous gas: physiopathology, etiology, prognosis and treatment. World J Gastroenterol 2009;15:3585-90. Crossref

Hair growth pattern in humans depends on age, sex, and race.1 Hypertrichosis refers to excessive hair growth that is inappropriate for a patient after consideration of the normal variation of an individual’s reference group.2 Hypertrichosis is different from ‘hirsutism’, which is caused by excessive androgen-sensitive hair growth.1 Hypertrichosis can be categorised into congenital versus acquired and generalised versus localised, and it may cause considerable psychological stress.3 Acquired localised hypertrichosis (ALH) following a fracture or cast application has been reported in different countries. In this case report, a Chinese boy with localised hypertrichosis in the right leg after application of a cast following right leg fracture is described. To the best of our knowledge, this patient represents one of the youngest reported cases.

In January 2014, a 28-month-old Chinese boy presented to the general out-patient clinic at Tseung Kwan O Hospital in Hong Kong with limping gait after removal of a cast applied for right leg fracture. During the consultation, the child was observed to have excessive hair growth on his right leg. He had a history of right leg fracture 6 weeks previously after he accidentally fell from a height of 1.5 m. He had consulted a private orthopaedic surgeon and a cast was applied for 6 weeks. After removal of the cast, he was noticed to have a lot of new hair growth on his right leg. There was no increased hair growth over the left leg or other body parts. There was no history of systemic or topical medication use before the onset of increased hair growth. The mother was concerned about whether any treatment was needed for the excessive hair growth.

On physical examination, there was significantly increased thick dark hair growth over the anterior and lateral parts of the right leg previously covered by the cast (Fig 1). There was no other skin change. The new hair growth caused no skin symptoms to the child. The child walked with a mild limping gait, but there was no limb deformity, muscle wasting, or bony tenderness.

The patient was diagnosed with ALH due to cast application. The patient’s mother was reassured about the benign, transient, and self-limiting nature of the condition. His limping gait was treated with physiotherapy. He was followed up at 3 months, when his gait had become normal and there was spontaneous complete resolution of the localised hypertrichosis (Fig 2).

There are many causes of ALH such as chronic irritation (eg skin overlying areas of thrombophlebitis or chronic osteomyelitis), friction (eg lichen simplex chronicus, insect bites, atopic eczema), or inflammation (eg chemical-induced dermatitis, ultraviolet irradiation, vaccination sites).2 It is not uncommon to find ALH following prolonged cast or splint application for various orthopaedic conditions. A Turkish study involving 117 patients showed that post-cast hypertrichosis might occur in up to one third of patients.4 The study showed that there was no sex predisposition, but the frequency peaked in the adolescent age-group.4 Post-cast ALH has been reported in paediatric and young adult patients in various countries from 1989 to 2013, but the prevalence in local Chinese patients is unknown.5 6 7 8 9 10 11 Complete resolution of hypertrichosis was noted at around 3 to 9 months after removal of the cast or splint.

One of the major mechanisms of hypertrichosis is conversion of vellus to terminal hair. Vellus hair is fine, non-pigmented, and produced by hair follicles located in the dermis. Vellus hair develops on almost all parts of the body, and its growth is not affected by hormones. Terminal hair is thick, pigmented, and produced by large hair follicles located in the subcutis. Terminal hair is found on sites where hair growth is affected by hormones, eg scalp, beard, axillae, and pubic area.12 Vellus-to-terminal switch on body sites that usually do not have terminal hairs will cause hypertrichosis. The underlying mechanism of this vellus-to-terminal switch is still poorly understood.13

Another major mechanism of hypertrichosis involves change in the hair growth cycle. Hair follicles undergo lifelong cyclic transformation in three stages: anagen, the active growth phase; catagen, the apoptosis-driven phase; and telogen, the resting phase followed by hair shedding.12 Hypertrichosis results when the hair follicles stay longer than usual in the anagen phase. Similar to vellus-to-terminal switch, control of the hair growth cycle is still not well understood.1

The pathogenesis of post-cast hypertrichosis after fracture is not well-established and different hypotheses have been postulated. Some authors suggested that prolonged cast application provides an occlusive, moist, and warm environment which, together with irritation caused by friction, promotes hair growth.11 Some authors, however, believe that the increase in regional blood flow to the bone following fracture provides abundant oxygen and nutrients that prolong the anagen phase of hair growth, resulting in transient hypertrichosis.6 This hypothesis is supported by the speculation that hypertrichosis has also been observed after splint application that does not occlude the injured area, suggesting that the fracture-healing process rather than the cast-occlusion effect led to hypertrichosis.10 Other hypotheses on the pathogenesis of ALH include transient cutaneous hyperaemia stimulating the hair follicles5 and reflex sympathetic dystrophy induced by immobilisation causing vasodilatation of the affected area and stimulating hair growth.7

Post-cast ALH is more commonly observed in children and young adults.4 This could be explained by age-related changes in hair growth. With ageing, the activity of the hair follicles declines and the hair growth rate decreases. Since older adult patients have a shorter anagen period of the hair growth cycle, ALH is less frequently observed in this age-group. Children and young adults do not have this unfavourable effect of the ageing process on hair growth to cancel stimulation of hair follicles after cast application, and therefore post-cast ALH is more commonly seen in this younger age-group.

Cases of ALH following fracture or cast application have been described by orthopaedic surgeons and dermatologists, but not in the primary care setting. Nonetheless, such cases may be encountered in primary care. Therefore, family physicians should be aware of the diagnosis and management of the condition and its implications for psychosocial consequences, since hypertrichosis may cause considerable emotional stress to patients due to the unsightly cosmetic appearance.10 We should address any psychological distress brought about by hypertrichosis and reassure patients and their parents about the benign and transient nature of ALH after cast application. In most cases, the abnormal hair growth will disappear within 6 months, as in this patient, and further investigation or intervention is not indicated. If, however, hypertrichosis causes cosmetic or psychological problems for the patient, hair removal—for example, by shaving or other mechanical methods—could be considered.2

1. Bertolino A, Freedberg I. Hair. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editors. Dermatology in general medicine. New York: McGraw-Hill; 1993: 671-96.

2. Wendelin DS, Pope DN, Mallory SB. Hypertrichosis. J Am Acad Dermatol 2003;48:161-79. Crossref

3. Vashi RA, Mancini AJ, Paller AS. Primary generalized and localized hypertrichosis in children. Arch Dermatol 2001;137:877-84.

4. Akoglu G, Emre S, Metin A, Bozkurt M. High frequency of hypertrichosis after cast application. Dermatology 2012;225:70-4. Crossref

5. Leung AK, Kiefer GN. Localized acquired hypertrichosis associated with fracture and cast application. J Natl Med Assoc 1989;81:65-7.

6. Kara A, Kanra G, Alanay Y. Localized acquired hypertrichosis following cast application. Pediatr Dermatol 2001;18:57-9. Crossref

7. Rathi SK. Localized acquired hypertrichosis following cast application. Indian J Dermatol Venereol Leprol 2007;73:367. Crossref

8. Leung AK, Wong AS. Localized acquired hypertrichosis associated with the application of a splint. Case Rep Pediatr 2012;2012:592092.

9. Ma HJ, Yang Y, Ma HY, Jia CY, Li TH. Acquired localized hypertrichosis induced by internal fixation and plaster cast application. Ann Dermatol 2013;25:365-7. Crossref

10. Harper MC. Localized acquired hypertrichosis associated with fractures of the arm in young females. A report of two cases. Orthopedics 1986;9:73-4.

11. Chang CH, Cohen PR. Ipsilateral post-cast hypertrichosis and dyshidrotic dermatitis. Arch Phys Med Rehabil 1995;76:97-100. Crossref

12. Wolff K, Johnson RA, Saavedra AP. Disorders of hair follicles and related disorders. In: Fitzpatrick’s color atlas and synopsis of clinical dermatology. New York: McGraw-Hill; 2013: 760-89.

13. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev 2001;81:449-94.