Click here to watch a video clip showing robotic-assisted laparoscopic Mitrofanoff appendicovesicostomy

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.

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).

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.

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.

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.

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 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.

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.

1. Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012;380:756-66. Crossref

2. Praga M, González E. Acute interstitial nephritis. Kidney Int 2010;77:956-61. Crossref

3. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol 2010;6:461-70. Crossref

4. Rossert J. Drug-induced acute interstitial nephritis. Kidney Int 2001;60:804-17. Crossref

5. Clarkson MR, Giblin L, O’Connell FP, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 2004;19:2778-83. Crossref

6. Kanofsky JD, Woesner ME, Harris AZ, Kelleher JP, Gittens K, Jerschow E. A case of acute renal failure in a patient recently treated with clozapine and a review of previously reported cases. Prim Care Companion CNS Disord 2011;13:PCC.10br01091.

7. An NY, Lee J, Noh JS. A case of clozapine induced acute renal failure. Psychiatry Investig 2013;10:92-4. Crossref

8. Mohan T, Chua J, Kartika J, Bastiampillai T, Dhillon R. Clozapine-induced nephritis and monitoring implications. Aust N Z J Psychiatry 2013;47:586-7. Crossref

Optic nerve aplasia is a very rare congenital anomaly that is typically unilateral, and is characterised by congenital absence of the optic nerve, central retinal vessels, and retinal ganglion cells.1 Bilateral cases are exceedingly rare. Various ocular anomalies are associated with it.

A female infant weighing 3225 g was born to a 26-year-old G1P1 female at full term via caesarean section because the umbilical cord was around the neck. She was found to have left microphthalmos on routine postnatal check-up in December 2013 in Hong Kong, at the age of 3 months. Family history was negative for ocular or other birth defects. Her mother was a housewife, with no history of any major illness during the pregnancy and antenatal workup was unremarkable. Physical examination was unremarkable with normal development for her age.

Eye examination of the infant at 4 months revealed left microphthalmos, and a left convergent squint with no definite visual following. The left pupil did not react to light stimulation and a persistent pupillary membrane was evident. Coloboma of the left optic disc was suspected. Fundus examination showed whitish choroidal atrophy with a flat optic disc on the left side. Right eye examination including fundus examination was unremarkable as were all blood tests and urinalysis.

Magnetic resonance imaging performed at 4 months revealed left microphthalmos, with no recognisable left optic nerve. The right optic nerve was present and normal in size. The optic chiasm was seen and slightly deviated towards the right side, likely related to the absence of the left optic nerve (Fig 1). Bilateral optic tracts and optic radiations were symmetrical. The septum pellucidum and corpus callosum were intact and all other cerebral and ocular structures were unremarkable (Fig 2).

Aplasia of the optic nerve is a rare congenital anomaly that is typically unilateral. It occurs sporadically in an otherwise healthy person without sexual or racial predilection,2 or any evidence of an inherited factor.

Prenatal history is usually normal, but the possible influence of external factors such as episodes of viral infection in the first trimester,3 acetone exposure, or smoking during pregnancy4 cannot be excluded.

The pathogenesis of optic nerve aplasia remains unclear although it was first described 140 years ago. Scheie and Adler5 suggested that the defect in aplasia was failure of the mesoderm to enter the fetal fissure and provide vascularisation of the retina and nerve tissue. Weiter et al6 doubted the defective mesodermal development, since the dural sheath (a mesodermal derivative) was present in the majority of their cases. Instead, they suggested that the ventral invagination of the optic vesicle causes nerve fibre misdirection and secondary atrophy. Yanoff et al7 postulated a primary failure of the ganglion cell to develop and send out axons, resulting in a lack of induction of mesodermal ingrowth including a lack of retinal blood vessel development. Hotchkiss and Green8 agreed that failure of mesodermal induction was secondary to third-order neuronal defect in the ganglion cell layer.

Plain X-ray can demonstrate a small optic foramen on the side of aplasia.9 Computed tomographic scan may show the globe and orbit on the affected side to be smaller than the normal side. Magnetic resonance imaging will show the absence of optic nerve on the affected side. The chiasm and lateral geniculate body may also appear small.10

Histopathological findings in optic nerve aplasia include the absence of ganglion cells and their axons as well as the absence of retinal vessels.7

According to many previous statements, aplasia of the optic nerve is a part of hypoplasia of the optic spectrum. According to an analysis performed by Alqahtani,2 of 42 cases in the literature, 29 were genuine aplasia of the optic nerve, while the remainder were hypoplastic optic nerve.

Unilateral aplasia of the optic nerve is often present in malformed eyes, with no abnormality in brain tissue. Possible malformations of the eye include microphthalmos, cataract, retinal dysplasia, coloboma of the iris and ciliary body, iris hypoplasia, malformation of the chamber angle, and persistent hyperplastic primary vitreous.11 No light perception is present in the affected eye and light stimulation elicits no direct or consensual pupillary response. Light stimulation of the normal eye results in a direct or consensual pupillary response.11 Possible malformation of the central nervous system includes hydranencephaly, orbital meningoencephalocele, and anencephaly.5 6

The prognosis of optic nerve aplasia is poor. There is no specific treatment and blindness occurs in the affected eye. Management of such cases is directed towards identifying any associated ophthalmological or neurological problems. Cavallini et al12 recommended ocular prosthesis in patients with associated microphthalmos, to enable normal development of the orbit, at least for aesthetic purposes.

Optic nerve aplasia should be suspected in a patient who presents with unilateral microphthalmos that is associated with the absence of central retinal vessels and ganglion cells. Magnetic resonance imaging is useful to screen for other associated intracranial abnormality.

1. Blanco R, Salvador F, Galan A, Gil-Gibernau JJ. Aplasia of the optic nerve: report of three cases. J Pediatr Ophthalmol Strabismus 1992;29:228-31.

2. Alqahtani J. Optic nerve aplasia: a case report and literature review. J Pediatr Neurosci 2008;3:150-3. Crossref

3. Ginsberg J, Bove KE, Cuesta MG. Aplasia of the optic nerve with aniridia. Ann Ophthalmol 1980;12:433-9.

4. Barry DR. Aplasia of the optic nerves. Int Ophthalmol 1985;7:235-42. Crossref

5. Scheie HG, Adler FH. Aplasia of the optic nerve. Arch Ophthalmol 1941;26:61-70. Crossref

6. Weiter JJ, McLean IW, Zimmerman LE. Aplasia of the optic nerve and disk. Am J Ophthalmol 1977;83:569-76. Crossref

7. Yanoff M, Rorke LB, Allman MI. Bilateral optic system aplasia with relatively normal eyes. Arch Ophthalmol 1978;96:97-101. Crossref

8. Hotchkiss LH, Green WR. Optic nerve aplasia and hypoplasia. J Pediatr Ophthalmol Strabismus 1979;16:225-40.

9. Little LE, Whitmore PV, Wells TW Jr. Aplasia of the optic nerve. J Pediatr Ophthalmol 1976;13:84-8.

10. Margo CE, Hamed LM, Fang E, Dawson WW. Optic nerve aplasia. Arch Ophthalmol 1992;110:1610-3. Crossref

11. Howard MA, Thompson JT, Howard RO. Aplasia of the optic nerve. Trans Am Ophthalmol Soc 1993;91:267-76; discussion 276-81.

12. Cavallini GM, Forlini M, Gramajo AL, et al. Optic nerve aplasia and microphthalmos: a case report. J Genet Syndr Gene Ther 2013;4:175. Crossref

Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition characterised by fibrosis and thickening of the dura mater. Diagnosis of idiopathic hypertrophic pachymeningitis requires a high index of suspicion, as its initial manifestation could be subtle clinically and radiologically. Idiopathic hypertrophic pachymeningitis has posed considerable diagnostic challenges to attending clinicians, including radiologists, neurologists, and ophthalmologists because of its highly variable presentation. Apart from clinical subtlety and variability, idiopathic hypertrophic pachymeningitis is also a great imposter because it can mimic other common and important neurological conditions such as prolactinoma.

A 28-year-old Chinese woman with a history of granulomatous mastitis 7 years previously was noted to have oligomenorrhoea, nausea, headache, and raised prolactin level of 1261.0 mIU/L (reference range [RR], 108.8-557.1 mIU/L) since March 2011. Her baseline hormone profile was otherwise normal. Plain magnetic resonance imaging (MRI) scan showed an enlarged pituitary gland of up to 1.6 cm (Figs 1a and 1b). At that time she was diagnosed with prolactinoma and treated with bromocriptine; her prolactin level was well-controlled subsequently.

After cessation of bromocriptine at the end of 2012, she developed periodic headache and flickering vision loss since May 2013. Her best-corrected visual acuities were 20/40 and 20/30 in her right and left eyes, respectively. She developed red colour desaturation of around 30%. Humphrey visual field 30-2 test showed superior field loss in the right eye, while the left eye was full field loss. Six weeks later her visual acuity decreased to 20/800 in the right eye and 20/400 in the left eye. She was given dexamethasone and her visual acuity increased to 20/20 and 20/16 in the right and left eyes, respectively. Other slit-lamp and fundal examinations were unremarkable. There was no papilloedema. There was no involvement of other cranial nerves. Glasgow Coma Scale Score was 15/15 throughout. Magnetic resonance imaging with contrast showed increased contrast enhancement and inflammation over the dura of the sella and cavernous sinus (Figs 1c and 1d). Her symptoms resolved and visual function recovered quickly with high-dose steroid. However, she developed steroid dependency since repeated attacks developed when the steroid was stopped.

Serial MRI scan showed progressive diffuse thickening of the pachymeningitis with disappearance of pituitary apoplexy, together with chronic otitis media (Figs 1c and 1d). Lumbar puncture showed 13 cm H₂O and lymphocytosis without organisms. Open biopsy of the meninges was performed and histology showed features of inflammatory infiltrates and vasculitis, but was negative for malignancy (Fig 2). Gene rearrangement polymerase chain reaction assay for immunoglobulin (Ig) heavy chain, T-cell receptor (TCR)–beta and TCR-gamma all showed no clonal peak. Polymerase chain reaction for Mycobacterium tuberculosis and culture for dural biopsy were also negative; IgG4 was 975 mg/L (RR, 61-1214 mg/L). Complete blood count showed normal haemoglobin, white blood cell, and platelet levels. Liver and renal function tests, serum calcium, creatine kinase, and lactate dehydrogenase levels were normal. Erythrocyte sedimentation rate was raised to 113 mm/h (RR, 0-20 mm/h). C-reactive protein was raised at 67.4 mg/L (reference level, <9.9 mg/L). In coagulation profile, activated partial thromboplastin time was slightly prolonged to 40.0 seconds (RR, 28.2-37.4 seconds). Autoimmune markers, including anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-DNA immunofluorescence test, anti-extractable nuclear antigen, anti-cardiolipin antibodies, and rheumatoid factors are all negative except for the presence of lupus anticoagulant. Complement C3 was normal while complement C4 was slightly raised to 0.42 g/L (RR, 0.1-0.4 g/L). Serum vitamin B12 level was 552 pmol/L (RR, 156-698 pmol/L) and serum folate level was 29.3 nmol/L (RR, 10.4-42.4 nmol/L); IgG4 was 975 mg/L. Virology screening—including human immunodeficiency virus, hepatitis B virus, and hepatitis C virus—was negative. Serum and cerebrospinal fluid Venereal Disease Research Laboratory tests were negative. Chest X-ray was clear with no features of tuberculosis or sarcoidosis.

The patient was initially treated with pulse steroid and was well-controlled by low-dose steroid. She remained symptom-free 6 months after biopsy.

Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition involving focal and/or diffuse thickening and fibrosis of the dura mater. Thickened dura mater with local mass effect may be pathognomonic of this condition. This pressure effect may serve as a mechanistic explanation of the observed neurological defect. As almost every part of the dura mater can be affected focally and/or diffusely, there is a highly variable clinical picture.1 2 Diagnosis is almost always made by exclusion of a large number of aetiologies, for example, infectious causes such as Lyme disease, syphilis, and M tuberculosis; inflammatory causes such as Wegener granulomatosis,3 rheumatoid arthritis, Behçet disease, and sarcoidosis (which is rare in Chinese people); and malignancy. In this patient, these tests were all negative, so the diagnosis of idiopathic hypertrophic pachymeningitis was made.

Demographically, the median age of patients with idiopathic hypertrophic pachymeningitis is 58.3 years (standard deviation, 15.8; range, 37-88 years).4 5 6 Only a few paediatric patients have been reported, with the youngest age being 2 years and 11 months in India.7 Our patient had early-onset disease. There are few data on ethnicity due to the rarity of the disease. Idiopathic hypertrophic pachymeningitis is extremely rare in Chinese people.

The exact aetiopathophysiology of idiopathic hypertrophic pachymeningitis is not known. It is believed to be autoimmune in origin.8 Lupus anticoagulant is a type of autoantibody that binds to phospholipid and protein, which is commonly associated with autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome.9 Our patient’s symptoms and signs did not fit into any diagnostic category of autoimmune disease. Only the presence of lupus coagulants might suggest that idiopathic hypertrophic pachymeningitis is a form of vasculitis, which might share some common phenomenon with other autoimmune diseases, although the true relationship is controversial.

Clinically, headache is by far the most common feature and the optic nerve is one of the most common cranial nerves to be involved, which was the case for this patient. Multiple cranial nerve involvement, ataxia, cortical blindness, psychosis, motor function disturbance, fever, convulsion, and/or loss of consciousness have all been reported.5 6 Yamada et al2 thought that the inflammatory thickening of the dura may cause damage to the superior hypophyseal artery resulting in subarachnoid haemorrhage and apoplexy in the anterior lobe of the pituitary gland. The posterior lobe was spared in their patient, who had a normal hormonal profile, unlike our patient. The initial enlarged pituitary gland with raised prolactin was more likely to result from the stalk effect than from true prolactinoma.

Granulomatous mastitis is a rare idiopathic chronic benign breast condition, which is believed to be autoimmune in origin, and mainly affects women of child-bearing age.10 Granulomatous mastitis is mainly diagnosed by exclusion of other diagnoses. To the best of our knowledge, this is the first case of idiopathic hypertrophic pachymeningitis reported with the association of granulomatous mastitis, possibly related to the scarcity of cases affecting menstruating women.

Idiopathic hypertrophic pachymeningitis is a rare condition with a highly variable clinical presentation making accurate and timely diagnosis difficult. Therefore the attending clinician should maintain high vigilance in the event of an atypical presentation of a presumably typical disease. Early diagnosis and prompt therapeutic intervention such as high-dose steroid may be the key to preserving vision as well as life.

1. Christakis PG, Machado DG, Fattahi P. Idiopathic hypertrophic pachymeningitis mimicking neurosarcoidosis. Clin Neurol Neurosurg 2012;114:176-8. Crossref

2. Yamada SM, Aoki M, Nakane M, Nakayama H. A case of subarachnoid hemorrhage with pituitary apoplexy caused by idiopathic hypertrophic pachymeningitis. Neurol Sci 2011;32:455-9. Crossref

3. Yokoseki A, Saji E, Arakawa M, et al. Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody. Brain 2014;137:520-36. Crossref

4. Yonekawa T, Murai H, Utsuki S, et al. A nationwide survey of hypertrophic pachymeningitis in Japan. J Neurol Neurosurg Psychiatry 2014;85:732-9. Crossref

5. Riku S, Kato S. Idiopathic hypertrophic pachymeningitis. Neuropathology 2003;23:335-44. Crossref

6. Kupersmith MJ, Martin V, Heller G, Shah A, Mitnick HJ. Idiopathic hypertrophic pachymeningitis. Neurology 2004;62:686-94. Crossref

7. Sharma PK, Saikia B, Sharma R, Gagneja V, Khilnani P. Pachymeningitis in a young child responded to antitubercular therapy: a case report. J Child Neurol 2014;29:NP92-5. Crossref

8. Masson C, Boukriche Y, Colombani JM. Inflammatory hypertrophic cranial pachymeningitis. Presse Med 2001;95:65-70.

9. Favaloro EJ, Wong RC. Antiphospholipid antibody testing for the antiphospholipid syndrome: a comprehensive practical review including a synopsis of challenges and recent guidelines. Pathology 2014;46:481-95. Crossref

10. Poovamma CU, Pais VA, Dolas SC, Prema M, Khandelwal R, Nisheena R. Idiopathic granulomatous mastitis: a rare entity with a variable presentation. Breast Dis 2014;34:101-4.

Psittacosis is a zoonotic disease caused by Chlamydophila psittaci, an obligate intracellular pathogen belonging to the family Chlamydiaceae. Since its first description in 1879, zoonotic and enzoonotic outbreaks have been reported worldwide.1 Transmission occurs through direct contact or inhalation of aerosols from dried faeces, feather dust, or respiratory secretions of infected birds. Individuals with occupational or recreational exposure to birds like bird fanciers and veterinarians are at greatest risk of infection. Person-to-person transmission is rare.2 The disease can range from subclinical infection to fatal pneumonia. Here, we report three cases of atypical pneumonia caused by C psittaci in Hong Kong.

A 62-year-old retired male presented in March 2014 with fever, headache, myalgia, cough, and yellowish sputum for 6 days. He had underlying diabetes mellitus, hypertension, gout, and renal impairment. He visited the local bird market frequently and had purchased two parrots before onset of symptoms. The parrots were well all along. On presentation, he was alert and stable and his temperature was 38.4°C. The oxygen saturation was 96% on room air. Chest examination revealed left lower zone crepitations. Chest radiograph showed left lower zone consolidation. He was suspected of psittacosis and was treated with ceftriaxone and doxycycline. His sputum was positive for C psittaci by polymerase chain reaction (PCR). Nasopharyngeal swab and sputum were also positive for influenza A virus subtype H3 by PCR. Oseltamivir was commenced. He was afebrile the next day and was discharged after 5 days of hospitalisation. Paired serum collected 12 days apart showed rising Chlamydia group titre from 40 to 80 by complement fixation test (CFT). The parrots could no longer be traced as the patient’s son released them.

A 55-year-old male construction site worker with hypertension was admitted in February 2014 with a 1-week history of fever, headache, generalised bone pain, and cough. He had travelled to Shanwei in China and bought a live chicken from a wet market 2 weeks earlier. On examination, his vital signs were stable and had a temperature of 40°C. The oxygen saturation was 98% on room air. Chest examination was normal. Chest radiograph showed right upper zone opacities. He was treated as a case of community-acquired pneumonia with amoxicillin-clavulanate, doxycycline, and oseltamivir. Sputum culture showed growth of commensals only. Nasopharyngeal aspirate (NPA) was negative for influenza viruses, Mycoplasma pneumoniae, and Chlamydophila pneumoniae by PCR. Oseltamivir was stopped. His fever subsided on day 3 and he was discharged after 4 days of hospitalisation. Complement fixation test of paired sera taken 2 weeks apart showed a rise in Chlamydia group titre from 20 to 80. Sputum was retrieved and was positive for C psittaci by PCR.

A 42-year-old female chef was hospitalised in February 2014 with fever, cough, yellowish and blood-stained sputum, and breathing difficulty for 1 week. She had no underlying illness. One week prior to her admission, she had travelled to Zhaoqing in China and bought live goose and chicken from a wet market. On admission, she was in respiratory distress and her temperature was 39.2°C. The oxygen saturation was 90% on 100% supplemental oxygen via non-rebreathing mask. Chest examination yielded coarse crepitations over the right side. Chest radiograph revealed right middle and lower zone consolidation, and left patchy haziness (Fig). On the same day, she was transferred to the intensive care unit. She required mechanical ventilation and extracorporeal membrane oxygenation (ECMO). She was treated as a case of severe community-acquired pneumonia with piperacillin-tazobactam, doxycycline, and oseltamivir. Sputum culture showed growth of commensals only. Sputum, NPA, and tracheal aspirate were negative for influenza viruses, M pneumoniae, and C pneumoniae by PCR. Urine was negative for Legionella pneumophila and pneumococcal antigens. She gradually improved and was extubated 3 days later, and ECMO was stopped on day 7. She was discharged on day 24 of hospitalisation. Paired serum drawn 12 days apart showed rising Chlamydia group titre from 80 to 640 by CFT. Polymerase chain reaction for C psittaci was positive in her stored sputum.

The laboratory profiles of the three cases on admission are summarised in the Table.

Psittacosis is an uncommon disease in Hong Kong. Since 2008, this has been made as a statutory notifiable disease. There were 11 confirmed cases and six probable cases reported until 2013.3 In 2012, there was an outbreak involving six staff working at the New Territories North Animal Management Centre in Sheung Shui.4

Chlamydophila psittaci is classified into nine genotypes (A to F, E/B, M56, WC) based on outer membrane protein A gene sequences, with differential host preference and virulence among the genotypes.1 It has been described in at least 460 bird species from 30 orders.5 Birds can shed the organisms when apparently healthy or overtly ill. Patient 1 had been exposed to asymptomatic parrots, belonging to the classic culprits, the psittacine birds (parrots, parakeets, budgerigars, cockatiels). Other domestic species—for examples, turkey, pigeon, goose, duck, chicken—can be affected and are often overlooked as potential reservoirs of infection.6 In patients 2 and 3, psittacosis was not suspected initially although the patients had been exposed to poultry in China. Chlamydophila psittaci is an emerging pathogen among chicken.7 In China, the prevalence of infection among market-sold chickens, ducks, and pigeons has been reported to be 13.32%, 38.92% and 31.09%, respectively.8 The substantial zoonotic transmission risk from domestic species should also be recognised.

Psittacosis is a systemic illness that affects several organ systems, and atypical pneumonia as in our cases is the most common manifestation. Patients typically present with influenza-like symptoms, which include high fever, headache, myalgia, and dry cough. Patient 3 complained of blood-stained sputum, which may occur occasionally.1 9 The headaches can be so severe as to suggest meningitis on presentation. Diarrhoea is common and can be the chief presenting complaint. Relative bradycardia, Horder’s spots, and splenomegaly are characteristic physical signs. There may be disparity between the auscultatory findings and radiographic changes of pneumonia. Segmental consolidation in lower lobe is the most common radiographic abnormality although normal chest radiograph has been reported in over 20% of cases. Hilar lymphadenopathy and pleural effusion are rare.10 The white cell count is usually normal or slightly raised, with mildly abnormal liver function. Our case presentations were consistent with psittacosis. However, it is indistinguishable clinically from other causes of atypical pneumonia like C pneumoniae. The severity ranged from mild-to-severe pneumonia requiring intensive care management and ECMO in our cases. Patient 1 had mild illness although co-infected with influenza A. This diversity of presentation is in agreement with other case series.9 The mortality rate can be approximately 15% to 20% without appropriate treatment but if properly treated, it is rarely fatal.11 Extrapulmonary complications such as endocarditis, myocarditis, renal disease, hepatitis, keratoconjunctivitis, arthritis, and encephalitis have also been described.

Chlamydophila psittaci is not covered during routine bacterial or viral workup. Definitive diagnosis can only be established by culture, serology, or PCR specifically targeting on C psittaci. Culture is time-consuming and requires level-3 biosafety facilities. Common serological assays include CFT, enzyme-linked immunosorbent assay, and microimmunofluorescence (MIF) test. The assays are neither sensitive nor specific but MIF test is regarded as more specific.12 However, there are still considerable cross-reactions between different species of the Chlamydiaceae family.1 Besides, a convalescent serum obtained at least 2 weeks apart is required to demonstrate the 4-fold rise in titre. In patient 1, the elevation in CFT titre was not significant and therefore diagnosis may be missed if relying on serology alone. Early use of doxycycline in this patient might have blunted the antibody response.13 In patients 2 and 3, serology results were available only retrospectively; PCR for C psittaci was performed subsequently to confirm the diagnosis. In our cases, a nested PCR based on 16S rRNA gene was used. The first-step PCR is genus-specific, followed by the second-step PCR that can detect C psittaci specifically.14 This method was demonstrated to be sensitive and specific for detection of C psittaci. When encountering respiratory illness with suspicion of psittacosis, PCR testing on respiratory specimens can offer a rapid and specific diagnosis.

Tetracyclines, in particular doxycycline, are considered to be the treatment of choice. In patients presenting with community-acquired pneumonia, addition of doxycycline to a beta-lactam–based empirical regimen can provide coverage for both psittacosis and other atypical pathogens. Defervescence usually takes place within 48 hours of treatment. Our patients showed significant improvement by day 3 of doxycycline treatment. The commonly recommended duration of treatment is at least 10 to 21 days to prevent relapse.9 Macrolides can be used as alternative therapy, but may be less efficacious in severe cases and gestational psittacosis.6 Although quinolones have in-vitro activity against C psittaci, their clinical effectiveness remains to be determined.6

Psittacosis often goes unrecognised because of the lack of distinctive symptoms and clinical suspicion. In patients with atypical pneumonia, a history of exposure to birds gives a very valuable diagnostic clue. Early diagnosis with PCR testing and timely initiation of appropriate antibiotics can reduce patient morbidity and mortality.

We thank the Public Health Laboratory Services Branch of the Centre for Health Protection for providing the laboratory testing of psittacosis.

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