Elston, John S. MD; Venning, Vanessa MD; Parks, Tom MD; Asher, Ruth MD
Section Editor(s): Miller, Neil R. MD
Department of Ophthalmology (JSE), Oxford Eye Hospital, Oxford, United Kingdom; Department of Dermatology (VV, TP), Churchill Hospital, United Kingdom; and Department of Cellular Pathology (RA), John Radcliffe Hospital, Oxford, United Kingdom.
Address correspondence to John S. Elston, MD, Department of Ophthalmology, Oxford Eye Hospital, Oxford OX3 9DU, United Kingdom; E-mail: firstname.lastname@example.org
The authors report no conflicts of interest.
A 69-year-old woman presented with an 18-month history of progressive facial asymmetry, the right eye appearing more prominent than the left. She also complained of tearing of the right eye and inability to close the eye tightly. She had noted recurrent focal superficial red skin lesions on the right brow that initially blistered and then healed over 2–3 weeks. She described similar lesions occurring on her hands and lower legs over the past 2 years that resolved after local steroid cream treatment prescribed by her primary care physician. The patient denied any disturbance in her vision, headaches, or other neurologic symptoms. Hearing was normal. Her medical history was unremarkable, and she was taking no current medication. She had smoked 15–20 cigarettes a day for 50 years. She had lived and worked in Lombok, Indonesia, for 8 years, returning to live in the United Kingdom 3 years before presentation.
On examination, the patient's best-corrected visual acuity was 20/20 bilaterally with normal visual fields. Extraocular movements were full, and the patient was orthophoric. There was no proptosis. The anterior and posterior segments of each eye were normal. There were foci of erythema and blistering on the right brow (Fig. 1A). Right facial weakness was evident and involved the orbicularis oculi disproportionately (Fig. 1B). Left facial nerve function was normal. After forceful bilateral eye closure, mid-facial fasciculations lasting 5–10 seconds were seen on the right side. Trigeminal sensory function was reduced in the first and second divisions on the right, including corneal sensation; motor function was normal. Bell phenomenon was preserved, and all other cranial nerve function was intact.
Routine hematologic and biochemical studies, including liver function tests, revealed no abnormalities. Serum immunoglobulins were normal as were inflammatory markers, including eosinophil sedimentation rate and c-reactive protein. The antinuclear antibody test and an autoantibody screening were negative. Varicella zoster virus–specific IgM antibody was negative as were both Lyme and treponemal serologies. Chest radiography was normal. MRI revealed no abnormalities other than age-related involutional changes and T2 hyperintensities consistent with microvascular disease in the deep white matter of both cerebral hemispheres. The orbits were normal. There was no space-occupying or inflammatory lesion in the pons, and both facial nerves and trigeminal nerves had normal imaging characteristics.
The patient's clinical signs gradually progressed. The right facial palsy increased, and she developed a right lower lid entropion. She also developed numbness in the distal lower limbs and increased frequency and persistence of the skin lesions. Neurological examination showed reduced sensation to temperature and touch below the knees and an anesthetic patch on the left palm. Knee flexion and extension were weak. The patient was referred for a dermatological assessment.
Drs Venning and Parks:
Dermatological examination revealed that the facial skin was shiny and thickened. A single eroded lesion was present on the nose on the right, the previous brow lesions having healed. Asymptomatic waxy infiltrated plaques were noted over the lower thighs and shins. These findings are nonspecific, and the differential diagnosis covers a range of pathologies, including many granulomatous disorders and skin infiltrations. Cutaneous sarcoidosis can cause nasal skin lesions and facial palsy. Primary dermatological and hematological malignancies, including mycosis fungoides, can present with atypical plaque-like lesions. Infections causing thickened plaques include tuberculosis (lupus vulgaris), nontuberculous mycobacterial infection, syphilis, cutaneous leishmaniasis, and leprosy. Multibacillary (MB) leprosy may cause plaques and papules that differ from the hypopigmented macules of paucibacillary disease.
As it was not possible to make a definitive diagnosis based on the clinical findings, a skin biopsy was obtained from a typical lesion on the patient's right shin (Fig. 2).
Histological sections from the specimen showed a diffuse infiltrate of macrophages filling the reticular dermis (Fig. 3A). The papillary dermis was spared. Although the infiltrate was composed mainly of macrophages, some of which displayed foamy cytoplasm and small scattered aggregates of lymphocytes, and plasma cells were also present. Small cutaneous nerves (Fig. 3B) were surrounded by macrophages and plasma cells indicating perineuritis and endoneuritis. Wade-Fite (modified Ziehl–Neelsen) staining revealed large numbers of acid-fast bacilli within macrophages (Fig. 3C), small cutaneous nerves, and endothelial cells. The features described are characteristic of MB leprosy.
Pathological Diagnosis: Mutibacillary Leprosy
The patient was treated with multidrug therapy for MB leprosy according to World Health Organization (WHO) guidelines, consisting of 600 mg of rifampicin once a month, 300 mg of clofazimine once a month, and 100 mg of dapsone once daily along with 30 mg of prednisone once daily. Within 6 weeks, she reported general malaise, back pain, and hoarseness of the voice; her skin lesions had worsened with diffuse dermal infiltration. The peripheral neuropathy also progressed, and at 12 weeks, her shins and forearm skin were marked from local trauma. There was also increased mucosal involvement. Her right lower lid entropion and lagophthalmos worsened with corneal exposure keratopathy for which she was scheduled for surgery. Before this could take place and 5 months after treatment had started, she developed an intractable cough and was diagnosed with lung cancer. She declined further treatment and died 3 months later.
A unifying diagnosis for the combination of slowly progressive facial palsy with muscle fasciculation, ipsilateral trigeminal sensory neuropathy (V1 and V2), and recurrent skin blistering in an otherwise healthy Caucasian woman covers a wide spectrum of potential pathologies.
The facial neuropathy with fasciculations suggested either intrinsic pontine pathology (tumor or inflammation) or chronic peripheral axonal compromise with ephaptic transmission due to, for example, schwannoma of the facial nerve. Sarcoidosis can present with facial palsy and involve other cranial nerves and the skin. Infections presenting with facial palsy, including Lyme borreliosis (which can also cause recurrent or migrating skin lesions and trigeminal neuropathy), as well as HIV and varicella infection, were considered. On a world-wide basis, leprosy is the most common infective cause of facial palsy.
Trigeminal sensory neuropathy can be the presenting sign of an autoimmune connective tissue disease (1), such as primary Sjögren syndrome, which can also cause cranial motor neuropathy. Perineural skull base lesions can also cause this clinical picture.
The morphology and characteristics of the skin lesions were not diagnostic. Herpes zoster ophthalmicus was considered in this case, but the lesions were recurrent and occurred elsewhere on the body. A skin biopsy was required to make the correct diagnosis of MB leprosy.
Leprosy is a chronic granulomatous disease caused by infection with Mycobacterium leprae. The infection is spread by respiratory droplets, but only a small proportion of infections (approximately 10%) lead to clinical disease with genetic determinants of cell-mediated immunity conferring protection on the majority. Clinical disease as classified by the WHO has a wide spectrum from the paucibacillary variant, characterized by high cellular immunity and low bacterial load to MB disease (as in our case), where cellular immunity is low and bacterial load is high. The spectrum of disease is also likely to be determined by host genetic heterogeneity. The incubation period is usually between 3 and 5 years (2).
The majority of new cases of leprosy occur in global areas of high endemicity. Since the start of the WHO leprosy elimination program in 1995, the global prevalence and annual incidence of leprosy has progressively declined. The remaining pockets of high endemicity are in parts of India, Burma, and Nepal. In endemic areas, awareness of the clinical presentation with peripheral neuropathy (90% of cases) and skin changes is high. Thus, the disease is recognized early and can be treated successfully in most cases. Ophthalmic complications (Table 1) are well recognized but rarely the presenting feature; however, 2.8% of patients with MB leprosy are visually impaired at presentation, and 11% have potentially blinding pathology (3). In addition, patients with MB leprosy who have completed treatment remain at risk of the development of new ocular complications, such as corneal opacity, that may be sufficiently severe as to be sight threatening (4).
In the United Kingdom, a small and declining number of cases of leprosy are identified annually, the majority occurring in immigrants from endemic areas, especially India. In a UK study of 28 patients with leprosy referred for treatment to the London Hospital for Tropical Diseases (5), most presented with a peripheral “glove and stocking” sensory neuropathy or an ulnar neuropathy with or without skin lesions. There was an average delay of 3.1 years between onset of symptoms and diagnosis. Of the 28 patients, 3 were Caucasian British who had acquired the disease while working abroad in endemic areas between 8 and 40 years.
Leprosy has not previously been described presenting with progressive facial weakness and fasciculation and ipsilateral trigeminal sensory neuropathy in a UK Caucasian. Moreover, muscle fasciculation, although previously noted in leprosy, is a very rare feature. It was recognized at presentation that this case was unusual, particularly taken with the unexplained cutaneous features, but the diagnosis of leprosy was not considered initially, and the importance of the patient's history of time spent in Indonesia not appreciated until disease progression occurred and a dermatological opinion was obtained.
The key to the diagnosis of exotic infections is an awareness of the current ubiquity of overseas travel and work, the potential importance of which may not be appreciated by the patient or the physician. With a multisystem presentation, the active involvement of colleagues from other disciplines is important. Leprosy is readily diagnosed by skin biopsy, and this is a standard dermatological procedure when a clinical diagnosis cannot be made. Early diagnosis and treatment of leprosy lead to an improved clinical outcome. It also militates against the spread of this disease in the country of residence.
© 2012 Lippincott Williams & Wilkins, Inc.