Multibacillary leprosy with an incubation period exceeding 50 years

Background

The incidence of leprosy has slowly declined over the last decade; however, there were still more than 200 000 cases reported globally in 2018.1 While uncommon in Australia, leprosy disproportionately affects Aboriginal and Torres Strait Islander people and migrants from leprosy endemic regions. These two populations comprised 95% of new cases in the most recent national data set.2 Consequently, a diagnosis of leprosy may be overlooked outside this demographic. Nonetheless, early recognition is important as effective antimicrobial therapy can eradicate the infection and prevent irreversible neurological disability.

Case presentation

A retired Caucasian man was admitted under the neurology team for the investigation of multiple mononeuropathies. His medical history included type 2 diabetes that was well controlled with a glycated haemoglobin of 4.8%, ischaemic heart disease with a previous non-ST segment elevation myocardial infarction, chronic obstructive pulmonary disease in the setting of a 60-pack year history of smoking and peripheral vascular disease. The patient had previously worked within the local government sector in rural Australia. Between 1964 and 1967, the patient supervised a rural public swimming pool that was used monthly by the local leprosarium. The patient swam in the pool and made use of the facilities on a number of these occasions. He had never lived or worked overseas.

In 2019, the patient developed a slowly progressive left foot drop, which worsened over a period of 6 months. He subsequently developed sensory loss in the left foot, which extended to involve the entire limb below the knee. He underwent nerve conduction studies which were consistent with a severe common peroneal nerve neuropathy at the fibular head.

Over the next 12 months, the patient developed a right foot drop with associated sensory loss to the level of the mid-shin. Approximately 21 months after the onset of his initial neurological symptoms, the patient noticed the appearance of multiple non-tender, non-pruritic macules and patches affecting the trunk and all four limbs. Following this, he developed weakness in the left hand with sensory loss in the fourth and fifth digits extending up to the elbow as well as left ear lobe and neck numbness.

At the time of his hospital admission, the patient had profound wasting of the left dorsal interossei with weakness of the second to fourth digits in abduction, adduction, flexion and extension. Thumb abduction and flexion were weak. This was clinically consistent with involvement of the median, ulnar and to a lesser degree radial nerve. There was loss of sensation in a left ulnar nerve distribution. Both ulnar nerves were thickened and palpable at the elbow. Right upper limb neurological examination was otherwise normal. He had bilateral lower limb weakness with absent movement in all planes at the ankles. There was loss of pinprick sensation, proprioception and vibration sense below the level of the knee on the right, and below the level of the groin on the left. The latter finding in the left leg was consistent with a sensory neuropathy involving the sciatic trunk, cutaneous femoral and lateral cutaneous nerve of the thigh. He had a high stepping gait and required a four-wheeled walker to mobilise. The patient also had reduced pinprick sensation in the left greater auricular nerve. This finding, in addition to more profound sensory loss distally in the lower limbs, was consistent with a predilection for sites with lower local temperatures. As seen in figure 1 and figure 2, he had a diffuse rash with patches and macules affecting the trunk and all four limbs. Individual lesions were not hypoanaesthetic, nor were they tender. There were no subcutaneous nodules. There was no madarosis, lagophthalmos, reduced corneal sensation or signs of exposure keratitis.

Investigations

Initial investigations revealed a mild normocytic anaemia with a haemoglobin of 120 g/L. White cell count, renal function, liver function, erythrocyte sedimentation rate, C reactive protein, complement 3/4 and immunoglobulins were normal. Subsequent investigations, including ACE levels, paraprotein screen and vasculitic screen, were normal. Nerve conduction studies showed distally predominant, multiple mononeuropathies in all four limbs, including bilateral ulnar nerves at the elbow, proximal left median nerve, bilateral common peroneal nerves, bilateral tibial nerves, bilateral sural nerves and subclinical bilateral radial nerve involvement. Representative waveforms from the nerve conduction studies are shown in figure 3 and figure 4. A punch biopsy of a lesion on the left thigh revealed granulomatous dermatitis without necrosis. A chest radiograph showed no parenchymal lesions or features of pulmonary sarcoidosis.

The patient proceeded to have biopsies of his left sural nerve, left peroneus brevis muscle and left lateral cutaneous nerve of the thigh. Both nerve specimens showed florid granulomatous inflammation with acid fast bacilli seen within foamy macrophages. Representative microscopy is shown in figure 5. A real-time PCR assay targeting a region of the rpoB gene of Mycobacterium leprae was positive. This was subsequently performed on the skin biopsy and also returned a positive result. The left sural nerve bacterial index was 2+ (1–10 bacilli per 10 high-powered fields). The morphological index was estimated at 17%. No recognised resistance mutations were detected in the rpoB, folP1 and gyrA genes.

Treatment

The patient was commenced on the WHO multidrug therapy regimen for multibacillary leprosy with clofazimine 50 mg/day, dapsone 100 mg/day, rifampicin 600 mg monthly and an additional clofazimine 300 mg monthly. The patient was provided with a case manager from the local public health unit who administered the monthly doses as directly observed therapy. Current and previous household contacts were referred to the public health unit for assessment and consideration of single-dose rifampicin chemoprophylaxis. The patient underwent a 3-week period of intensive inpatient rehabilitation with input from physiotherapy, occupational therapy and social work. He was fitted with bilateral orthoses for footdrop and was discharged with rehabilitation in the home services.

Outcome and follow-up

At the time of writing, the patient had completed 9 months of a planned 12-month treatment course with unchanged sensorimotor deficits relative to baseline. The patient’s progress was complicated by a type 1 reaction 1–2 months into therapy manifesting as symptomatic neuritis and new cutaneous lesions. Motor and sensory impairment remained stable. He was commenced on prednisolone 50 mg/day with significant improvement in symptoms and without further progression of established impairment. Prednisolone was gradually tapered over a 6-month period.