A 7-year-old Nepalese boy with unremarkable past health was admitted in July 2013 with a 2-week history of headache, dizziness, and vomiting that subsided spontaneously. On admission, he was afebrile with unremarkable neurological and fundal examination.

He had been living in Nepal until the age of 5 years and then immigrated to Hong Kong. He recently travelled to Nepal but had otherwise no contact history with pigs or febrile persons.

Blood tests were unremarkable except mildly elevated erythrocyte sedimentation rate of 26 mm/h. Lumbar puncture yielded normal cerebrospinal fluid (CSF) white cell count, and protein and glucose level. Culture of blood and CSF was negative.

Initial contrast computed tomographic brain showed two subcentimetre (7 mm and 9 mm) left parieto-occipital adjacent rim-enhancing lesions (Fig a) with T1-weighted hypointense and T2-weighted/fluid-attenuated inversion recovery hyperintense signal on contrast magnetic resonance imaging (MRI) [Fig b]. Significant perifocal oedema and mass effect with compression on the left occipital horn was noted. Magnetic resonance spectroscopy showed a significant lipid-lactate peak (Fig c), decreased N-acetylaspartate, and no elevated choline. No amino acid peak was identified. Perfusion imaging with arterial spine labelling showed no elevated regional cerebral blood flow (Fig d). Contrast MRI of the spine showed no leptomeningeal enhancement, intradural nor extradural spinal mass lesions.

Subsequent extensive investigations of blood (including anti-Taenia solium immunoglobulin G), CSF, urine and stool for tuberculosis and T solium were performed, and all results were negative.

Overall review of the clinical presentation, travel history, laboratory and imaging findings, and the two cerebral rim-enhancing lesions were suggestive of an infective process, in particular, neurocysticercosis or tuberculosis.

After thorough investigations and interdepartmental discussions, it was decided to treat the patient as a probable case of neurocysticercosis and a course of empirical albendazole and prednisolone was prescribed.

The patient remained asymptomatic after treatment. Follow-up MRI performed after 2 and 5 months (Fig e) showed reduction in size of the two cerebral rim-enhancing lesions (3 mm and 1 mm), as well as the extent of perifocal oedema.

Neurocysticercosis is a parasitic infection of the central nervous system by T solium (ie pork tapeworm) usually through accidental ingestion of contaminated food containing its eggs. It has been a diagnostic challenge in developed areas owing to its infrequent occurrence, low sensitivity of serological tests, and highly variable and non-specific manifestations, both clinically and radiologically. It is further complicated by clinical and radiological features that overlap considerably with tuberculosis infection, particularly in tuberculosis-endemic areas.

A few international diagnostic criteria for neurocysticercosis have been proposed, and aim to stratify the diagnostic strength based on the interpretation of clinical, radiological, serological, and epidemiological information. One of the most widely accepted revised criteria was proposed by Del Brutto et al in 2001,1 and classifies patients into two degrees of diagnostic certainty—definitive or probable. Definitive diagnosis requires the presence of one absolute criterion or two major plus one minor epidemiological criteria. Probable diagnosis can be made if there are one major plus two minor criteria; one major plus one minor and one epidemiological criteria; or presence of three minor plus one epidemiological criteria. Four categories of criteria based on their diagnostic strength are shown in Table a.1

The diagnostic dilemma in our index case was the lack of characteristic imaging features and positive serological proof, hence difficult differentiation from tuberculosis infection, i.e. tuberculomas. Other common differential diagnoses of cystic lesions include pyogenic abscesses and metastases. Both were unlikely in our patient given the aseptic clinical presentation, normal blood and CSF profiles, absence of a known primary and lack of associated radiological findings (eg cerebritis, ventriculitis or meningeal enhancement). Biopsy or excision of the cerebral cystic lesions might offer a straightforward histopathological diagnosis, however, it is an invasive investigation and imposes potential risks.

Attempts have been made in the literature to distinguish cysticercosis and tuberculosis neurological infection by combined interpretation of the clinical, radiological, and serological features.2 3 4

Clinically, tuberculomas are more often associated with increased intracranial pressure and focal neurological deficits, whereas patients with neurocysticercosis are usually less symptomatic or present with seizures.2

Radiologically, the imaging findings of neurocysticercosis are variable, depending on the stage and location of infestation. A diagnostic dilemma lies in those who present with intracranial cystic lesions without presence of scolex, and that may be present in both neurocysticercosis and tuberculosis. Table b shows some MRI imaging features that may help distinguish the two diagnoses.2 3 4 5

Based on the neuroimaging features and the revised diagnostic criteria, a probable diagnosis of neurocysticercosis was made: presence of lesions compatible with neurocysticercosis that resolved after treatment with albendazole, and a history of travelling to an endemic area.

Neurocysticercosis is an uncommon parasitic infection of the central nervous system in Hong Kong and requires a high degree of clinical suspicion for diagnosis. Despite the advances in neuroimaging, accurate diagnosis is still sometimes difficult, which is related to the pleomorphic disease nature and significant overlapping features with tuberculosis. A combination of proper interpretation of diagnostic criteria and imaging findings is helpful in making the diagnosis without invasive and potentially harmful investigations.

1. Del Brutto OH, Rajshekhar V, White AC Jr, et al. Proposed diagnostic criteria for neurocysticercosis. Neurology 2001;57:177-83. Crossref

2. Rajshekhar V, Haran RP, Prakash GS, Chandy MJ. Differentiating solitary small cysticercus granulomas and tuberculomas in patients with epilepsy. Clinical and computerized tomographic criteria. J Neurosurg 1993;78:402-7. Crossref

3. Garg RK, Kar AM, Kumar T. Neurocysticercosis like presentation in a case of CNS tuberculosis. Neurol India 2000;48:260-2.

4. Garg RK. Diagnosis of intracranial tuberculoma. Indian J Tuberc 1996;43:35-9.

5. Pretell EJ, Martinot C Jr, Garcia HH, Alvarado M, Bustos JA, Martinot C; Cysticercosis Working Group in Peru. Differential diagnosis between cerebral tuberculosis and neurocysticercosis by magnetic resonance spectroscopy. J Comput Assist Tomogr 2005;29:112-4. Crossref

Hyperphenylalaninaemia refers to the clinical condition characterised by increased amounts of phenylalanine in blood and other tissues. It can result from either a deficiency of phenylalanine hydroxylase (PAH) or defects in synthesis or regeneration of tetrahydrobiopterin (BH4), a cofactor for PAH (Fig 1).

We describe a 2-year-old boy who was referred by the Maternity Child Health Clinic to the Department of Paediatrics in June 2014 for assessment of developmental delay. He was the second child in his family, born at term and following an uneventful pregnancy to non-consanguineous Chinese parents. His birth weight was 3475 g. He was formula-fed from birth, then gradually weaned to a normal toddler diet. Family history was unremarkable. The mother was from Hubei, a province in Central China, and father was from Shenzhen, a major city in Southern China. The 5-year-old brother was well and there were no developmental concerns.

The boy’s early developmental milestones were unremarkable. He developed social smile at 1 month of age, sat unsupported at 8 months, and walked independently at 1 year and 8 months. He started saying single words at 15 months but at the age of 2 years was still saying only a few single words and no phrases. Also he was noted to be hyperactive with behaviour that was at times difficult to control. His physical growth was satisfactory. His head circumference was 48.5 cm (50th centile), weight 14.1 kg (90th centile), and height 87 cm (50th centile). There were no dysmorphic features and no abnormalities were detected on physical examination. His hair was slightly brownish.

Initial baseline investigations revealed normal blood count and liver, renal, and thyroid function. Urine organic acid analysis showed markedly elevated phenylalanine metabolites including phenyllactic, 3-phenylpyruvic, and phenylacetic acids. Plasma phenylalanine level was markedly elevated at 1948 µmol/L (reference range [RR], 26-91 µmol/L) and tyrosine was 47 µmol/L (RR, 24-115 µmol/L). Urine biopterin was mildly elevated at 5.0 µmol/mmol creatinine (RR, 0.5-3.0) while neopterin was normal at 1.7 µmol/mmol creatinine (RR, 1.1-4.0). Erythrocyte dihydropteridine reductase activity was normal. A BH4 loading test was performed to check for BH4 responsiveness according to standard protocol.1 Blood for phenylalanine and tyrosine was checked serially at 8, 16, and 24 hours after each administration of 20 mg/kg BH4 (Kuvan) orally on day 1 and day 2 of the loading test. No appreciable drop in blood phenylalanine level was observed confirming BH4 non-responsiveness.

All coding exons and flanking introns of the PAH gene (reference sequence NM_000277.1) were sequenced using the standard Sanger method. A heterozygous missense mutation c.860T>C was detected in exon 8 of the PAH gene. This mutation changes the highly conserved leucine at position 287 to proline (p.Leu287Pro) [Fig 2]. Another mutation affecting the same amino acid p.Leu287Gly has been reported previously in patients with phenylketonuria (PKU).2 In-silico analyses by four prediction software (PolyPhen-2, SIFT, Mutation Taster, PON-P2) also consistently predicted that the mutation is pathogenic. Therefore, PAH c.860T>C (p.Leu287Pro) is highly likely to be a pathogenic mutation. The mother was a carrier of this missense mutation. PAH gene dosage analysis by multiplex ligation probe amplification (SALSA MLPA probemix P055-C1 PAH) did not detect any PAH gross deletion or duplication. Therefore, the second PAH mutation of this patient remained unidentified.

The patient was started on a phenylalaninere-stricted diet after diagnosis. Special formula XP-2 powder from SHS was used as the phenylalanine-free and tyrosine supplement source. With dietary advice and close supervision, his phenylalanine levels gradually came down to 300 to 500 µmol/L while tyrosine levels were maintained at 50 to 80 µmol/L over the following 6 months. It is too early to report on his progress in terms of development and behaviour consequent to better control of the blood phenylalanine level.

We believe this is the first reported case of a locally born child with classic PKU in Hong Kong. Although a low phenylalanine diet was commenced promptly upon diagnosis, the cognitive impairment that has occurred as a result of the unrecognised long-standing hyperphenylalaninaemia is likely irreversible. Other than this patient reported here, two other classic PKU patients are being followed up at the authors’ metabolic clinic. Both patients were born in Guangzhou, the capital city of Guangdong province in South China. They were diagnosed through the newborn screening programme in Guangdong province. With good dietary compliance, both children have achieved normal growth and development.

This year marked the 56th anniversary of PKU newborn screening. Effective newborn screening programmes worldwide including those in China have identified thousands of infants with PKU and prevented intellectual disability through early diagnosis and treatment. Yet in Hong Kong the need for PKU screening has never been seriously addressed. Over the last 30 years, newborn screening in Hong Kong has remained unchanged with cord blood screening for G6PD (glucose-6-phosphate dehydrogenase) deficiency and congenital hypothyroidism. The current practice of newborn screening lags behind the rest of the world, and has never been challenged because for years there have been only scant cases of 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and no classic PKU cases reported locally. In the absence of newborn screening, why has only PTPS deficiency and no classic PKU patients been identified in Hong Kong? One reason could be that individuals with PTPS deficiency often present with more complex neurological manifestations and are more likely to undergo extensive investigations. On the contrary, those with classic PKU present with variable degrees of intellectual disability and behavioural problems and no overt neurological signs, and may not have been as extensively investigated. In addition, there is a general misconception among practising clinicians in Hong Kong that PKU is a disease of the Caucasian population. Even if it does affect the Chinese population, only the Northern Chinese are affected. As such, plasma amino acid or urine organic acid profile may not have been routinely requested for investigation in children with unexplained developmental delay, intellectual disability, behavioural problems, or autistic spectrum disorders. Further, these investigations may not be as widely available in non–hospital-based private laboratories.

Without a territory-wide newborn screening programme, it is impossible to ascertain the true incidence of PKU in Hong Kong. Irrespective of whether Hong Kong does have a different PKU incidence compared with the rest of China, the presence of confirmed cases locally provides a strong argument for diagnosis and treatment of affected individuals at the earliest instance rather than after symptomatic presentation. Hong Kong cannot afford to have more intellectual disability as a result of the unavailability of PKU screening. Until this programme becomes universally available, we advocate plasma amino acid and urine organic acid analysis to be incorporated into the diagnostic workup for all children with unexplained developmental delay, intellectual disability, behavioural problems, and autistic spectrum disorders.

1. Blau N, Hennermann JB, Langenbeck U, Lichter-Konecki U. Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies. Mol Genet Metab 2011;104 Suppl:S2-9. Crossref

2. Bardelli T, Donati MA, Gasperini S, et al. Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia. Mol Genet Metab 2002;77:260-6. Crossref

In August 2014, an 18-year-old boy with no prior history of coronary or cardiac disease presented to our tertiary cardiovascular and thoracic surgery hospital in Turkey with crushing substernal chest pain, nausea, and vomiting that had persisted for 1 hour. He had started work as a barman at a beach club 3 months earlier and denied any use of off-label drugs. His first electrocardiography (ECG) was normal with sinus rhythm (heart rate, 90 beats/min; Fig 1a). The patient, however, was tachypnoeic and reported a heavy squeezing chest discomfort. On physical examination, the pain was not relieved by position change and increased continuously. Blood pressure was 142/75 mm Hg and pulse oximetry showed oxygen saturation to be 94%. Chest auscultation was normal, as was chest X-ray. Cardiomegaly and pneumothorax were absent and the mediastinum was not widened.

Smoking was the only risk factor for developing coronary artery disease in this young patient. Hypertension, diabetes mellitus, hyperlipidaemia, family history of heart disease, and obesity were absent as risk factors for coronary artery disease.

The patient was thought to have myocarditis and ibuprofen was prescribed for symptom relief. The pain worsened, however, and ECG showed widened QRS complexes (right bundle branch block pattern in precordial derivations) with a rate of 112 beats/min (Fig 1b). The ECG was interpreted as idioventricular rhythm. Bedside transthoracic echocardiography was performed and left ventricular anterior wall hypokinesis with 40% ejection fraction was observed. Clopidogrel and acetylsalicylic acid were started and immediate coronary angiography (CAG) was performed to identify the cause. A significant stenosis of the mid-segment of the left anterior descending (LAD) artery with a fresh thrombus image was present with distal TIMI-3 flow (Thrombolysis In Myocardial Infarction grade 3, which implies normal flow that fills the distal coronary bed completely) [Fig 2a]. Right coronary artery and left circumflex artery were normal. Since the patient’s haemodynamic parameters were stable with TIMI-3 distal blood flow in the LAD, conservative treatment with intravenous glycoprotein 2b/3a (GP-2b3a) inhibitor was prescribed. After successful infusion of GP-2b3a without any complications, control CAG was performed (Fig 2b). Complete dissolution of thrombus was observed and left ventricular anterior hypokinesis was reversed.

The patient’s laboratory findings were all within normal range except markers of myocardial damage. Troponin I level was 24 µg/L. Platelet count and liver function tests were normal, as was clotting panel. The patient’s blood was screened for factor V Leiden mutation, prothrombin gene mutation, MTHFR gene mutation, protein C activity, protein S activity, plasminogen activator inhibitor–1 activity, homocysteine levels, and anti-cardiolipin antibodies. No secondary aetiology was evident that could account for such thrombus formation in an 18-year-old boy so he was further questioned about drug use. This time he admitted the use of marijuana 1 hour prior to the onset of intense chest pain.

Acute myocardial infarction (AMI) is the leading cause of death in North America and Europe.1 Despite this, AMI in an 18-year-old teenage boy is very rare. In our case the possible causes of thrombophilia were excluded and smoking of cannabis was thought to be the main cause of AMI.

Recent cannabis use is associated with acute coronary syndrome and can lead to severe cardiovascular problems and sudden death, not only in people at increased cardiovascular risk but also in young people without any medical history or risk factors.2 The effects of cannabinoids are primarily mediated by the activation of cannabinoid receptors that are present in a variety of tissues including the brain (basal ganglia, pars reticulata of the substantia nigra, entopeduncular nucleus, globus pallidus, putamen, cerebellum, hippocampus, and cerebral cortex) and cells of the immune system, spleen, blood vessels, and the heart.3

The pharmacological effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2 that are widely distributed in the cardiovascular system, have been well described. A dose-dependent increase in heart rate up to 100% of basal rate occurs 10 to 30 minutes after beginning to smoke.4 Most users experience an increase in blood pressure especially while supine4 although postural hypotension after smoking marijuana is common. Tolerance to this drug can occur with frequent repeated use.5 Another harmful effect of smoked marijuana is associated with an increase in carboxyhaemoglobin, resulting in decreased oxygen-carrying capacity6 and subsequent demand-supply mismatch by decreasing oxygen transportation to the heart. This mechanism is suggested to underlie atherosclerotic stable coronary disease and concomitant cannabinoid use. Nonetheless in our case, the patient was too young and the lesion appearance on CAG was suggestive of a small plaque rupture with superimposed thrombus formation rather than stable atherosclerotic disease. Acute myocardial infarction associated with cannabinoid use and with normal coronary artery has been reported in the literature. Ours is an interesting case report associated with cannabinoid inhalation and superimposed thrombus formation detected by CAG. In our patient, implantation of a stent in the LAD artery was not an option because the lesion was thought to be thrombotic. Dissolution of the thrombus was achieved with GP-2b3a infusion.

Clinicians are reminded of this very rare aetiology of acute coronary syndrome and its management among young patients. Bearing in mind the increasing use of drugs such as marijuana and other synthetic cannabinoids among young people, management of associated cardiac problems is vital. A CAG should be performed whenever drug abuse is suspected in any patient who presents with chest pain. If a thrombotic lesion is detected on CAG, infusion of GP-2b3a may dissolve the thrombus.

1. Griffin BP, editor. Manual of cardiovascular medicine. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2009: 1.

2. Casier I, Vanduynhoven P, Haine S, Vrints C, Jorens PG. Is recent cannabis use associated with acute coronary syndromes? An illustrative case series. Acta Cardiol 2014;69:131-6.

3. Járai Z, Wagner JA, Varga K, et al. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci USA 1999;96:14136-41. Crossref

4. Johnson S, Domino EF. Some cardiovascular effects of marihuana smoking in normal volunteers. Clin Pharmacol Ther 1971;12:762-8. Crossref

5. Benowitz NL, Jones RT. Cardiovascular effects of prolonged delta-9-tetrahydrocannabinol ingestion. Clin Pharmacol Ther 1975;18:287-97. Crossref

6. Aronow WS, Cassidy J. Effect of marihuana and placebo-marihuana smoking on angina pectoris. N Engl J Med 1974;291:65-7. Crossref

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.

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.

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.

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.

No conflicts of interest were declared by the authors.

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

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