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Q1: What were these two diagnostic procedures?
A liver biopsy and a sural nerve biopsy (fig 1).
A transjugular liver biopsy specimen disclosed granulomatous hepatitis with well defined epithelioid granulomata, with no caseation, throughout the parenchyma and in portal tracts, but negative for fungi, acid-fast bacilli, and with no polarisable material.
The sural nerve biopsy disclosed epineurium intensely infiltrated with monocytic cells in a perivascular distribution and mononuclear cells diffusely in the endoneurium. All fascicles showed uniform severe deletion of myelinated fibres, but demyelinated axons were not seen. The conclusion was that this represented severe acute on chronic axonal degeneration.
Q2: What is the underlying diagnosis?
The mediastinal lymphadenopathy, granulomatous hepatitis, hypercalcaemia, nerve biopsy findings consistent with axonal (sarcoid) neuropathy and the raised serum angiotensin converting enzyme (SACE) level all were consistent with the unifying diagnosis of sarcoidosis.
Peripheral neuropathy is a feature of many systemic diseases.
Clinical neurological examination with nerve conduction studies provides the best pathway for reaching a definitive diagnosis.
Nerve biopsy is a useful diagnostic tool for specific cases, particularly those thought to be secondary to sarcoidosis or a vasculitis.
Clinicoradiological findings in conjunction with histological evidence of non-caseating granulomas is central to the diagnosis of sarcoidosis.
Sarcoid neuropathy is largely an axonal neuropathy, although acute demyelinating polyneuropathies have been described.
Q3: What treatment is there, and what is the prognosis?
Corticosteroids are the firstline treatment for the manifestations of sarcoidosis. The rationale being the affect on mononuclear phagocytes and T-lymphocyte activity, both of which are heavily implicated in the pathogenesis of the disease. The dose and duration of treatment should be based on clinical and laboratory evidence for the severity of dysfunction and the response to treatment. Most patients with asymptomatic disease should not be treated unless the pathology affects ocular, myocardial, and renal tissue or calcium metabolism as all these can have significant long term clinical implications for the patient.
Ultimately, sarcoidosis shows a variable response to treatment leading to either monophasic or chronic, remitting, and relapsing phases. Frequently, relapses are seen when the dose of corticosteroids is tapered. To prevent this a slower and more prolonged process is then required. Some evidence suggests an additional agent improves outcome in 10%–20% of patients.1
This patient received prednisolone 60 mg, and later azathioprine 100 mg was started with immediate improvement in liver function, neuropathy, SACE, and hypercalcaemia.
Sarcoidosis is a multisystem granulomatous disorder with an incidence of about 15 per 100 000 and a peak onset in the 20–40 age group. It is commoner in black patients. Several abnormalities of immune function suggest an autoimmune or virally triggered aetiology, but this remains largely mysterious. The key histological feature is granuloma formation with a central collection of modified mononuclear phagocytes (epithelioid cells) and giant cells sharing the same cytoplasm with multiple nuclei. The damage this causes is secondary to mass effect.2,3
It is a true multisystem disease, but most often involves the lungs and intrathoracic lymph nodes. It can also cause uveitis, skin changes, hepatosplenomegaly, cardiac dysfunction, renal impairment and nephrocalcinosis, and central nervous system abnormalities. Hypercalcaemia which is secondary to high circulating 1,25 dihydroxy vitamin D3 levels (due to extrarenal elaboration of 1-α-hydroxylase by granuloma macrophages) is seen in about 10% of cases. Peripheral neuropathy is rare, seen in only 5% of cases.4
Sarcoid peripheral neuropathy is, in most cases, an axonal polyneuropathy.5 This case was unusual in that there was clear electrophysiological evidence of a (upper limb) demyelinating symmetrical sensory motor polyneuropathy, whereas the sural nerve biopsy disclosed severe acute on chronic axonal degeneration associated with a marked epineural perivascular infiltrate.
Sarcoidosis is an important diagnosis to make, as there is a good response in most cases to immunosuppression, conventionally with steroids. Azathioprine can be used adjunctively to reduce the steroid dose burden. In summary we present a case of a rare treatable cause—sarcoidosis—of a common symptom