A 53-year-old woman, menopausal for 4 years and with a previous kidney transplant presented with a 3-year history of excessive facial and body hair that required daily shaving in January 2008 (Fig 1). She had had no postmenopausal bleeding or gynaecological disease. She was prescribed immunosuppressants and corticosteroids but no hormones. There was no acne or hoarseness of voice. Examination revealed frontal balding and excessive hair over her chin, both shins, and lower abdomen with mild clitoromegaly. Serum testosterone was 19 nmol/L (reference range, 0.35-2.65 nmol/L); 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulfate (DHEAS) levels were normal. Adrenocorticotropic hormone and cortisol levels were normal after overnight dexamethasone suppression test. Her follicle-stimulating hormone, luteinising hormone, thyroid-stimulating hormone, and prolactin levels were also normal. Serum oestradiol was in the premenopausal range (298 nmol/L). Transvaginal ultrasound showed a normal uterus with endometrial thickness of 5 mm and no adnexal masses.

Questions:

1. What are the differential diagnoses?

2. What further investigations are helpful?

3. How should the patient be managed?

Answers:

1. Androgen-secreting tumours of the ovary or adrenal gland.
Hirsutism involves excessive terminal hair growth in a masculine distribution in women. It can occur as a side-effect of immunosuppressants, eg cyclosporin with gingival hyperplasia and hirsutism. Nonetheless virilisation is uncommon. Cyclosporin should be changed to tacrolimus when hirsutism occurs.
Virilisation (development of male characteristics in women) occurs in less than 1% of patients with hirsutism. When it occurs (temporal hair recession and clitoromegaly in this patient) androgen-secreting tumours of the ovaries or adrenals should be suspected, particularly when onset is sudden with rapid progression.

2. Patients with virilisation should have serum testosterone, 17-OHP, and DHEAS checked. Serum testosterone level of >200 ng/dL (ie 6.94 nmol/L or 3 times normal) and/or DHEAS level of >700 µg/dL (ie 24.3 nmol/L) are indicative of virilising tumours.1 2 Computed tomography (CT) of the adrenals and pelvis should be considered. Ultrasonography of the pelvis may be difficult and not diagnostic in menopausal women because the ovaries are small and steroid-secreting tumours can be <1 cm in diameter.3 In this patient, normal levels of DHEAS and 17-OHP made adrenal tumour and congenital adrenal hyperplasia unlikely. Ovarian virilising tumours have to be suspected. Preoperative CT pelvis showed a 1-cm cyst in her right ovary.

3. Endometrial aspirate was performed, there was no hyperplasia or malignancy. She underwent laparotomy and bilateral salpingo-oophorectomy. There was a 1-cm yellowish tumour in the right ovary. The left ovary appeared normal. Hysterectomy was not done as the uterus was densely adhered to the bowel (history of peritoneal dialysis). Histology confirmed stromal luteoma and hyperthecosis in both ovaries without malignancy (Fig 2). After surgery, her testosterone level normalised. Hair re-grew over her frontal region and her body hair reduced.

Ovarian steroid cell tumours account for 0.1% to 0.2% of all ovarian tumours, and are composed of cells resembling steroid-secreting cells.4 Steroid cell tumours of small size and confined to the ovarian stroma are conventionally designated stromal luteomas and are usually associated with stromal hyperthecosis in adjacent stroma. They can have oestrogenic and/or androgenic manifestations with postmenopausal bleeding or virilisation, and are associated with endometrial hyperplasia or carcinoma.5 Hysterectomy and bilateral salpingo-oophorectomy is advised as some of these tumours may have malignant potential.

1. Somani N, Harrison S, Bergfeld WF. The clinical evaluation of hirsutism. Dermatol Ther 2008;21:376-91. Crossref

2. Hunter MH, Carek PJ. Evaluation and treatment of women with hirsutism. Am Fam Physician 2003;67:2565-72.

3. Outwater EK, Wagner BJ, Mannion C, McLarney JK, Kim B. Sex cord–stromal and steroid cell tumors of the ovary. Radiographics 1998;18:1523-46. Crossref

4. Hayes MC, Scully RE. Stromal luteoma of the ovary: a clinicopathological analysis of 25 cases. Int J Gynecol Pathol 1987;6:313-21. Crossref

5. Yamada S, Tanimoto A, Wang KY, Shimajiri S, Sasaguri Y. Stromal luteoma and nodular hyperthecosis of the bilateral ovaries associated with atypical endometrial hyperplasia of the uterus. Pathol Int 2009;59:831-3. Crossref

A 33-year-old Indian male was hospitalised for a 3-day history of headache and left lower limb weakness in December 2014. He had experienced no fever or seizures. He had visited New Delhi, India, the year before. Physical examination revealed the patient to be fully conscious with left lower limb monoparesis. There was no sensory deficit. Computed tomography (CT) revealed a superior parietal intra-axial lesion with a calcified focus (Fig 1a). Magnetic resonance imaging (MRI) delineated a 2 x 1.5 x 1.5 cm circumscribed hypointense cystic lesion with a contrast-enhancing wall and an eccentric intracystic signal with perilesional oedema (Figs 1b to 1d). Differential diagnoses included neurocysticercosis, brain abscess, brain metastasis, and malignant glioma. Craniotomy for excision was performed in view of the possibility of malignancy and the surgically accessible superficial location of the lesion. Intra-operatively, a firm capsular mass containing thick opaque material was seen (Fig 2a). Histology revealed a cysticercus within a fibrous capsule, compatible with the diagnosis of neurocysticercosis (Figs 2b and 2c). A 2-week course of oral albendazole was commenced and the patient was discharged with full recovery.

Neurocysticercosis is the most common parasitic infection of the central nervous system (CNS) caused by the larval form of Taenia solium. The peak age of incidence is between 25 and 35 years1 and the condition is endemic to the Indian subcontinent, coastal North Africa, sub-Saharan Africa, Latin America, and China. The main mode of transmission is by faecal-oral ingestion of tapeworm embryos.1 2 Consumption of contaminated poorly cooked pork is a less-frequent alternative source of infection since pigs are intermediate hosts.2 3 Within 72 hours of ingestion, larvae known as oncospheres are released and pass through the intestinal wall into the circulation, subsequently depositing in the CNS, retina, and skeletal muscle as cysticerci.1 2 The parasite can remain viable in the brain for several years after which it undergoes calcific degeneration.3 In endemic areas, the most common presentation is epilepsy, responsible for 30% of cases.1 Focal neurological deficits may occur including cranial nerve palsy due to basal meningitis. Obstructive hydrocephalus develops when lesions occupy the fourth ventricle.1 2

Characteristic radiological features include dystrophic calcification on CT imaging, cyst wall contrast enhancement on T1-weighted MRI and identification of the pathognomonic scolex, an eccentric focus of enhancement representing the tapeworm’s head, best delineated with fluid-attenuated inversion recovery sequences (hole-with-dot sign).3 4 Brain abscess or metastases are important differential diagnoses as they are also similarly located at the grey-white matter junction of the middle cerebral artery distribution, associated with disproportionately significant perilesional cerebral oedema and classically exhibit heterogeneous contrast enhancement. Malignant glioma was less likely in our patient since they are morphologically more infiltrative, and the present lesion was well-circumscribed. For this patient, the major distinguishing feature that supported a diagnosis of neurocysticercosis was the presence of dystrophic calcification on CT and, in retrospect, the presence of a scolex on MRI. Absolute criteria for a definitive diagnosis are either histological parasitic proof, imaging demonstration of a scolex, or subretinal parasites on fundoscopy (Table5). Serological enzyme-linked immunoelectrotransfer blot detection of anti-cysticercus antibodies or cerebrospinal fluid enzyme-linked immunosorbent assays are adjunctive investigations.1 6 Management of active neurocysticercosis includes antiepileptic drug administration, anti-inflammatory glucocorticoid therapy, and definitive antiparasitic therapy with albendazole (15 mg/kg per day) or praziquantel (50 mg/kg per day) for 2 to 4 weeks.1 Surgical excision is reserved for cysts that cause mass effect, hydrocephalus, or if the diagnosis is unclear.2

In an era of increasing migration and international travel, patients from developing countries who present with seizures, raised intracranial pressure symptoms, or focal neurological deficit should be suspected of having neurocysticercosis when characteristic imaging findings are identified. In probable cases, a trial of antiparasitic therapy is recommended with serial scans arranged to monitor treatment response.

1. Garcia HH, Nash TE, Del Brutto OH. Clinical symptoms, diagnosis, and treatment of neurocysticercosis. Lancet Neurol 2014;13:1202-15. Crossref

2. Zymberg ST. Neurocysticercosis. World Neurosurg 2013;79(2 Suppl):S24.e5-8.

3. Dhesi B, Karia SJ, Adab N, Nair S. Imaging in neurocysticercosis. Pract Neurol 2015;15:135-7. Crossref

4. Lerner A, Shiroishi MS, Zee CS, Law M, Go JL. Imaging of neurocysticercosis. Neuroimaging Clin N Am 2012;22:659-76. Crossref

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

6. Gekeler F, Eichenlaub S, Mendoza EG, Sotelo J, Hoelscher M, Löscher T. Sensitivity and specificity of ELISA and immunoblot for diagnosing neurocysticercosis. Eur J Clin Microbiol Infect Dis 2002;21:227-9. Crossref

A middle-aged man admitted with abdominal pain and anaemia in December 2015. A computed tomographic (CT) angiogram demonstrated a superior indentation with focal narrowing in the proximal celiac axis (Fig 1). Conventional superior mesenteric arteriogram demonstrated prominent collaterals, and retrograde flow of contrast from the superior mesenteric artery (SMA) to the hepatic arteries (Fig 2). It was likely related to chronic compression of the proximal celiac artery. Low insertion of the median arcuate ligament (MAL) can be found in normal asymptomatic people. In this case, prominent collaterals and the retrograde flow from the SMA supported the diagnosis and may have explained his symptoms. In symptomatic cases, surgical division of the median arcuate ligament is the mainstay of treatment.

The MAL is a fibrous arch that unites the diaphragmatic crura on either side of the aortic hiatus. The crura pass superior and anterior to surround the aortic opening and to join the central tendon of the diaphragm. The ligament usually passes superior to the origin of the celiac axis. The insertion of the ligament may be low and therefore crossover the proximal portion of the celiac axis, causing a characteristic indentation. If it is significantly compressed on the celiac axis, this will compromise vascular flow and produce symptoms.

The MAL syndrome was first described in 1963 by Harjola1 and in 1965 by Dunbar et al.2 The definition of the syndrome relies on a combination of both clinical and radiographic features. Clinically, they described a classical triad of chronic postprandial abdominal pain, epigastric bruit, and weight loss.3 4 Extrinsic compression of the celiac trunk by the MAL occurs in 10% to 24% of patients.1 Usually, patients are asymptomatic and the classical triad is not always present, presumably due to collateral supply from the superior mesenteric circulation.1 2 The disease typically occurs in young patients and is more common in thin women who may present with epigastric pain and weight loss.1 The abdominal pain may be associated with eating, but not always.1 On physical examination, an abdominal bruit that varies with respiration may be audible in the mid-epigastric region. Symptoms are thought to arise from compression of the celiac axis with consequent compromised blood flow.

The diagnosis of celiac artery compression is traditionally made following conventional angiography. The use of thin-section multidetector CT and three-dimensional imaging techniques has greatly improved the ability to non-invasively obtain detailed images of the mesenteric vessels. Compression of the celiac axis by the MAL produces characteristic findings visible on CT angiography. Computed tomographic angiography can play a role in the diagnosis of this condition by demonstrating the characteristic focal narrowing of the celiac artery (Fig 1) with a hooked appearance that distinguishes this condition from other causes of celiac artery narrowing, such as atherosclerotic disease. Indentation of the origin of coeliac artery is exacerbated during the expiratory phase. Repeating CT on inspiration can often distinguish clinically significant narrowing from transient compression seen only during expiration in some patients, and is how most abdominal CT studies are performed.1

The majority of affected patients have no symptoms, thus radiographic finding of celiac axis compression alone may not be significant, unless it is correlated with clinical symptoms. Severe compression occurs in approximately 1% of patients.1 Severe stenosis will result in post-stenotic dilatation, and in some cases, the celiac axis will be fed by the SMA via the pancreaticoduodenal arcade. This was evident on the angiogram of our patient with prominent collaterals and retrograde flow from the SMA (Fig 2). His CT angiogram showed a characteristic hooked focal narrowing at the superior proximal celiac artery (Fig 1).

The surgical management of MAL syndrome is controversial.1 2 Surgical treatment in severe cases is advocated, particularly in cases with post-stenotic dilatation and collateral vessels (Fig 2), by division of the ligament. A laparoscopic approach is being increasingly adopted. Celiac angioplasty and stenting by endovascular means may be a future hot topic.2

1. Harjola PT. A rare obstruction of the coeliac artery: report of a case. Ann Chir Gynaecol Fenn 1963;52:547-50.

2. Dunbar JD, Molnar W, Beman FF, Marable SA. Compression of the celiac artery and abdominal angina. Am J Roentgenol Radium Ther Nucl Med 1965;95:731-44. Crossref

3. Horton KM, Talamini MA, Fishman EK. Median arcuate ligament syndrome: evaluation with CT angiography. Radiographics 2005;25:1177-82. Crossref

4. Duffy AJ, Panait L, Eisenberg D, Bell RL, Roberts KE, Sumpio B. Management of median arcuate ligament syndrome: a new paradigm. Ann Vasc Surg 2009;23:778-84. Crossref

A 54-year-old man was referred to the genetic clinic with familial nail dysplasia in September 2012 (Fig 1). On further questioning, he reported recurrent knee pain due to patellar dislocation. There was no elbow involvement or renal problem. A skeletal survey was performed in view of his skeletal complaint (Fig 2). His family history was significant: his paternal grandfather, father, and two of his paternal uncles also had nail dysplasia and knee problems, but had undergone no formal medical assessment. What is the diagnosis?

The combination of nail dysplasia, patella hypoplasia, and iliac horn led to the clinical diagnosis of nail-patella syndrome (NPS). This syndrome is also known as Fong disease or hereditary osteo-onychodysplasia. Multiple organ systems are affected including the nails, the eyes, the kidneys, and the skeleton. The clinical presentation of NPS can be highly heterogeneous and is summarised in the Table.1 2 It is a rare autosomal dominant disease with a prevalence of about 1 in 50 000 newborn.1 It is highly penetrant but with significant intra- and inter-familial variability in expression.

The diagnosis of NPS is usually based on clinical findings. It is straightforward when the classic tetrad of abnormal nails, elbows, knees, and iliac horns are present. Nonetheless molecular genetic testing should be considered when the diagnosis is in doubt, or when prenatal or pre-implantation diagnosis is desired. The LMX1B gene is the only gene known to be associated with NPS. Sequence analysis would identify the LMX1B gene mutation in 85% of cases of NPS.

LMX1B gene sequencing was performed for this patient (Fig 3) and revealed a missense mutation LMX1B NM_002316.3}:c.[175T>C];[=];LMX1B{NP _002307.2}:p.[Cys59Arg];[=]. This changed the 59th amino acid from cysteine to arginine in the LIM-A domain of the LMX1B protein. It was located in an evolutionarily highly conserved region and has been reported in the literature to be associated with NPS. Therefore, it was considered to be pathogenic.3

To date, more than 150 mutations of the LMX1B gene have been reported, but no clear genotype-phenotype correlation has been demonstrated. LMX1B has been demonstrated in animal models to be involved in multiple developmental functions including dorso-ventral patterning of the limb bud, and cellular differentiation in the kidney. Nonetheless the exact pathogenesis of NPS has not been elucidated.4

Upon initial diagnosis, comprehensive renal, orthopaedic, and ophthalmological assessments are essential. The renal manifestation strongly affects the long-term prognosis. Kidney involvement occurs in 30% to 50% of patients, but kidney failure only occurs in 3% to 5%.2 Since nephropathy may not develop until later in life, prospective monitoring is essential for all NPS patients. Primary open-angle glaucoma or ocular hypertension occurs in 10% of NPS patients so regular eye surveillance is also warranted. Nail-patella syndrome is an autosomal dominant disorder with a 50% chance of occurrence in offspring, thus genetic counselling is essential (Box2). Genetic testing of other at-risk family members, and prenatal and pre-implantation genetic diagnoses are possible only if the disease-causing mutation is known in the index patient.

1. Bongers EM, Gubler MC, Knoers NV. Nail-patella syndrome. Overview on clinical and molecular findings. Pediatr Nephrol 2002;17:703-12. Crossref

2. Sweeney E, Fryer A, Mountford R, Green A, McIntosh I. Nail-patella syndrome: a review of the phenotype aided by developmental biology. J Med Genet 2003;40:153-62. Crossref

3. Clough MV, Hamlington JD, McIntosh I. Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients. Hum Mutat 1999;14:459-65. Crossref

4. Chen H, Lun Y, Ovchinnikov D, et al. Limb and kidney defects in LMX1B mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat Genet 1998;19:51-5. Crossref

A 79-year-old man with lymphoma was admitted for chemotherapy in November 2014. During his admission, he complained of acute onset of left eye pain with loss of vision. There was no history of previous eye disease or injury.

On examination, his left eye had no light perception and intra-ocular pressure was raised to more than 50 mm Hg. There was left eye proptosis, chemosis, and oedema over the eyelid. There was no fundal view. B-scan performed by the ophthalmologist showed increased vitreous echogenicity. A complete blood picture showed low levels of haemoglobin (104 g/L) and thrombocytopenia (13 x 10⁹ /L), and total white cell count reduced to 0.69 x 10⁹ /L. Blood was taken from the central line for culture. Computed tomographic scan of the orbit was performed to look for intra-orbital haematoma as the platelet level was low. Computed tomographic scan showed left proptosis, left eyelid swelling, and increased soft tissue stranding in the retro-ocular space (Fig 1). The lens was dislocated into the posterior chamber and the density of vitreous humour was increased when compared with the right globe. The difference in densities between the two globes was exaggerated at a follow-up scan 6 hours later (Fig 2). Overall radiological findings were compatible with severe inflammation of the globe with pus in the posterior chamber complicated by lens dislocation. The patient was diagnosed with endophthalmitis and antibiotic treatment was started. The patient began to have pustular discharge from a ruptured corneal ulcer and subsequent evisceration of the eye was required. The specimen and the initial blood culture were positive for Bacillus species. The organism was sensitive for vancomycin and gentamicin.

Endophthalmitis can be classified broadly into endogenous or exogenous and can cause permanent blindness. Exogenous endophthalmitis is usually due to trauma or postoperative infection. Endogenous endophthalmitis is commonly due to bacteraemia and immunocompromised patients are at particular risk.

Endogenous endophthalmitis is relatively uncommon, accounting for 2% to 8% of all endophthalmitis cases. Staphylococcus aureus, Bacillus cereus, Escherichia coli, Neisseria meningitidis, and Klebsiella are common pathogens.1 Bacillus cereus is a highly virulent organism as it can produce toxins that trigger severe intra-ocular inflammation and can cause complete loss of vision or destruction of the globe within 24 to 48 hours.1 2 Patients may end up with enucleation and permanent loss of vision. Intravenous drug abusers are prone to Bacillus infection.3 The cause of Bacillus infection in our patient was unknown although the central venous catheter was a potential culprit.

This article illustrates the radiological features of endophthalmitis. It is usually a clinical diagnosis although imaging may be required in complicated cases. The prognosis for Bacillus endophthalmitis is poor despite vigorous treatment.

1. Callegan MC, Engelbert M, Parke DW 2nd, Jett BD, Gilmore MS. Bacterial endophthalmitis: epidemiology, therapeutics, and bacterium-host interactions. Clin Microbiol Rev 2002;15:111-24. Crossref

2. Kumar N, Garg N, Kumar N, Van Wagoner N. Bacillus cereus panophthalmitis associated with injection drug use. Int J Infect Dis 2014;26:165-6. Crossref

3. Hatem G, Merritt JC, Cowan CL Jr. Bacillus cereus panophthalmitis after intravenous heroin. Ann Ophthalmol 1979;11:431-40.