Mononeuritis Multiplex as Initial Manifestation of Pure Neuritic Leprosy—A Forgotten Cause: Clinical, Electrodiagnostic and Pathologic Correlations
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.293485
Source of Support: None, Conflict of Interest: None
Keywords: Hansen's disease, leprosy, mononeuritis, nerve biopsy, pure neuritic leprosy
Neuropathy does pose as a diagnostic conundrum with literally thousands of potential etiologies and does represent a potentially frustrating, time consuming and costly clinical scenario. What is the chance of correctly determining the pathologic type and etiology of a neuropathic disorder? This clinical dilemma requires a well-defined pragmatic algorithm for the evaluation of neuropathy with a need to set the direction and level of aggressiveness of the evaluation, since neurologists fall into two polar groups: (a) Pragmatists (aiming at minimal possible investigations to solve the clinical problem) and (b) Completists (aiming to eliminate every possibility). An ideal clinical approach should not have an umbrella “one size fits all” strategy of evaluation with an unnecessarily expensive “shotgun” approach. Neuropathies have numerous causes and diverse presentations; hence, a systematic, logical, and “pattern recognition” approach is needed for cost-effective diagnosis, especially of treatable neuropathies.
Hansen's disease (HD) looms still as a public health problem. Although both skin and nerve involvement usually occur together in leprosy, there can also be nerve involvement without any primary skin lesion. This atypical phenotype is called Pure neuritic leprosy (PNL). This phenotype may remain undiagnosed for a longer time compared to leprosy with dermatologic features since those with skin lesions often get an early dermatology referral and a patient presenting with neuritic symptoms per se often seeks treatment in the neurology or medicine departments. M. leprae, an intracellular obligate bacterium, with selective neurotropism to Schwann cells of the rich plexus of nerves in the superficial dermis, intradermal, and intracutaneous nerves that forms the pivotal neurobiologic underpinning of this disease.
According to Indian studies, PNL constituted about 4–18% of leprosy patients.,,,,,, A recent published study of a 7-year clinicopathological study of Hansen's neuritis (HN) from Mangalore (Karnataka, South India) documented 13 out of 18 cases to have PNL. In this study, there were six cases having borderline tuberculoid (BT) histology, followed by three cases of (borderline) BB, two cases each of BL (borderline lepromatous), and one case each of burnt-out HN and TT (Tuberculoid leprosy) morphology among the 13 PNL cases. In view of the distinctive absence of lepromatous cutaneous stigmata, the diagnosis of PNL is indeed challenging and the proof of leprosy as the etiology requires histological confirmation resorting to nerve biopsy. In addition, we reiterate the need to be aware of the various faces of leprosy, the nuances of HD as a “great imitator,” its mimics and chameleons [Table 1]. The varied, atypical, and unusual clinical presentations of HD underscore the need for interdisciplinary awareness not only between the neurologist and dermatologist but also include the ophthalmologist, rheumatologist, otolaryngologist, and the dentist. This is imperative to prevent the misdiagnosis since the disease is eminently treatable.
A 20-year-old graduate student with an unremarkable medical history presented with a two years insidious onset of numbness over region of the left medial maleolus. Over a span of six months, he noted sequential progression in his numbness to involve the medial aspect and heel/calcaneal area of left sole, then the lateral aspect of the left sole and finally the anterolateral aspect and shin area of his left leg. After 6 months he noticed slipping of his footwear from the left leg. These symptoms were not accompanied by trophic ulcers, painless wounds, skin changes, positive sensory neuropathic symptoms (tingling, paresthesia, dysesthesia) or evidence of cranial neuropathies. There was no history of skin lesions, contact with a person suffering from leprosyor a family history of neuropathy.
General physical and systemic examination proved unremarkable. Positive neurological findings were sensory abnormalities of a mononeuropathy multiplex pattern to all modalities of sensations involving the superficial peroneal, with differential grade of sensory deficits of a non-stocking type affecting the deep peroneal, Lateral plantar, Medial Plantar, calcaneal branch of tibial nerve, and sural nerves only on the left side [Figure 1]. There was no motor weakness except for weakness of the left Adductor hallucis and the left ankle tendon jerk was not elicitable on Jendrassik manoeuvre (Gr 0 DTR). Cutaneous examination did not reveal any lesions suggestive of leprosy, trophic ulcers or deformities. There was a non-tender nerve thickening of lateral popliteal nerve and posterior tibial nerve.
Investigations were directed towards mononeuritis multiplex (MM). Complete hemogram, ESR, C reactive protein, fasting, and postprandial blood sugars, and serum biochemistry were normal. Vasculitic workup that included antinuclear antibodies profile, perinuclear antineutrophil cytoplasmic antibodies (pANCA), serum Angiotension converting enzyme, and serum cryoglobulins were unremarkable. Virology screening for hepatitis virus and HIV ELISA were negative. His slit skin smear (SSS) from multiple sites for AFB-Myco leprae was negative.
Nerve conduction studies were remarkable for a markedly reduced compound action potentials (CMAPs) of left posterior tibial and absent superficial peroneal, sural, saphenous, medial, and lateral plantar SNAPs with normal onset latencies and velocity of sensory and motor conductions on the left side indicating an asymmetric left multiplex sensory more than motor axonal mononeuropathy multiplex. Electromyography studies revealed significant abnormal spontaneous activity and scattered voluntary motor unit activation over the abductor hallucis muscle, and abductor digitiquinti muscle. A limited high-resolution ultrasonography of posterior tibial nerves at the left ankle and proximal to the medial malleolus showed hypoechoic areas with focal thickening with loss of the normal fascicular pattern. A sural nerve biopsy established the diagnosis as borderline leprosy (BB disease spectrum) with a negative Fite-Faraco stain. (Bacteriologic index 0) [Figure 2]. With the sural nerve biopsy establishing the diagnosis of Hansen's disease, and the clinical phenotype of PNL presenting as isolated left leg axonal sensorimotor mononeuritis multiplex, he was initiated on multibacillary multidrug therapy (BB-MDT) consisting of Dapsone 100 mg daily, Clofazamine 50 mg daily and 300 mg monthly, and rifampicin 600 mg monthly for one year. On a 1 year follow up, the patient's condition improved with no reactions during treatment and a significant improvement in both motor and sensory deficit.
In contradiction to the “Global leprosy elimination by the year 2000” campaign, it is imperative to take cognizance of the fact that the incidence of new cases are rising especially from Asian endemic countries such as India, Nepal, and Myanmar, all with incidence rate of greater than 20/100,000 population.
Moneuritis multiplex is asymmetrical, asynchronous, usually painful involvement of at least two non-contiguous nerves leading to sensory and/or motor neuropathy. The differential diagnosis of MM is quite heterogeneous comprising of inflammatory, metabolic, infectious, rheumatologic, hematologic, and neoplastic disorders [Table 2]. Leprosy is the most common treatable cause of neuropathy in the world. Furthermore, India contributes to more than 50% of new cases detected globally every year. Hence early diagnosis is quintessential for the rapid diagnosis and implementation of treatment which would prevent disease progression, morbidity, and improve the patient's functional state. In this regard, the challenges that could involve both the dermatologist and the neurologist will be when HD presents without the typical dermatologic features. PNL phenotype may remain undiagnosed for a longer time compared to HN with skin lesions since those with skin lesions often get an early dermatology referral and a PNL patient often seeks consultation in medicine or neurology specialty. This should prompt the diagnosis of PNL in tropical countries and in India when India is documented to contribute to more than 50% of new cases detected globally every year.
The Indian Association of Leprologists (IALs) included the distinct form of “neural leprosy” in their official six group classification in 1955 and named it “polyneuritic leprosy”. In 1982, IAL renamed the nomenclature of “polyneuritic leprosy” as “PNL”. Nevertheless, PNL is a rare uncommon presentation and distinct subtype of leprous neuropathy. It is more common in men and it is most common in the 15-30 age group. Neural leprosy is undoubtedly difficult to diagnose in the absence of skin lesions and necessarily mandates a histological confirmation. This case merits discussion among treating physicians in endemic and non-endemic areas not only to be cognizant of the different phenotypes of Neuro-Hansen's disease since HD is eminently treatable, but it is of cardinal importance to note the various 'mimics and chameleons' that poses as diagnostic challenges. In literature, it is stated that first affected area in the legs is over the shin and dorsal part of the foot and not over the toes; however it is interesting to note that in our case it first involved the sole of feet in a patchy distribution, only later spreading to involve the typical regions.
We underscore the recent advancements in the diagnostic armamentarium, and the need to usemultiple analytical tools for proper and early diagnosis of PNL [Table 3] in order to differentiate it from other causes of non-leprosy neuropathies presenting as mononeuropathy multiplex. High resolution ultrasonography ultrasonography and ultrasound-guided Fine-needle aspiration cytology (FNAC) and cytomorphological features of nerve aspirate are indeed simpler, quicker and easy, less invasive, cost effective outpatient procedure, and an alternative diagnostic modality to nerve biopsy in PNL. Leprosy is the commonest cause of MM in the Indian sub-continent. In the appropriate clinical context, leprosy should not be a forgotten cause, instead should be included in the differential diagnosis of MM.
Leprosy remains a major health problem in developing countries especially in the “top two” countries of India and Brazil. A 'multidisciplinary awareness' of atypical presentations of Neuro-Hansen's disease and HN (including PNL) is therefore mandatory among the allied specialties such as dermatologists, neurologists, ophthalmologists, otolaryngologists, orthopedic surgeons, and rheumatologists. Nerve biopsy is an efficient tool to diagnose PNL and differentiate it from other causes of non-leprosy neuropathies presenting as mononeuropathy multiplex. This case is of considerable practical importance to the clinician confronted with diagnosing leprosy neuropathy without the typical dermal involvement.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The first author had presented “Recognizing the Many Faces and Diagnostic Challenges of Leprous Neuropathy; A Neurologist's Perspective” as an Invited speaker at the 21st Dermazone South and 8th Cuticon 2017 Conference in November at Mangalore.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]