Interesting and unusual clinical presentations in leprosy at a referral center

Abstract

Background:

Leprosy is a disease of declining global endemicity but is still an important health-care problem in India. Pure neural leprosy is an important subset of presentations of leprosy in India. Leprosy is a known disease of the skin and nerves, but cases of pure neural involvement are relatively less. We hereby present 10 cases of pure neural leprosy in which the diagnosis of leprosy was difficult with routine methods.

Materials and Methods:

The study was conducted at the main referral center and satellite clinics of our organization. A retrospective analysis of patient records for the last four years was undertaken to identify patients presenting with predominantly neurological manifestations and uncommon presentations including those without skin lesions. The medical records of the patients were used as source of data. All the patients were subjected to a detailed clinical examination and bacteriological examination with slit-skin smears. Investigations like nerve biopsy, electromyography, and nerve conduction studies were done in patients with diagnostic difficulties.

Results:

Patients presented with neurological symptoms like paresthesias (60%), diminished sensations (40%), nonhealing ulcers (30%), and blisters (20%). All except one had thickened nerves on clinical examination. Slit-skin smear was negative in all but one patient. Nerve biopsy confirmed the diagnosis of leprosy in seven cases.

Conclusion:

Pure neural leprosy is difficult to diagnose with routine methods. The diagnosis should be considered, especially by neurologists and dermatologists, who are more likely to see such patients with predominant neural manifestations. The diagnosis should be confirmed with nerve biopsy to prevent delay in therapy and associated complications.

INTRODUCTION

Leprosy, a disease of high endemicity in India, is claimed to be showing a decline in mean prevalence in the country.[1] However, the detection of new cases is relatively static and it has been observed that clinical manifestations of leprosy appear to be changing.[1] This poses a great challenge for clinicians to diagnose leprosy in time and initiate therapy to prevent complications of untreated disease.

During the last four years, we have encountered cases presenting with predominantly neural manifestations with no or minimal cutaneous manifestations. We share our experience related to 10 such cases that we studied retrospectively in last few years which probably could have been difficult to detect in a field situation.

MATERIALS AND METHODS

The study was conducted at the main referral center and satellite clinics of our organization. The center carries out operational and clinical research along with providing outpatient management of both referred and self-reporting leprosy cases and reaction management. The patients seen are self-reporting as well as referred to the center from other hospitals, private clinics, and peripheral centers.

These cases were referred basically for diagnostic reasons and were selected for study in view of unusual presenting features which made the diagnosis of leprosy difficult with routine methods.

The medical records of the patients were used as the source of data. All patients were subjected to a detailed clinical examination by trained medical officers and to a bacteriological examination with slit-skin smears. Higher investigations like electromyography (EMG)/nerve conduction studies (NCS) and nerve biopsy were done in seven patients. Profiles of two illustrative cases are given below.

Case 1

A 40-year-old female was referred with complaints of blisters on the right arm, forearm, and hand since two years. The patient had a history of tingling numbness in the right upper and lower extremity dating six years back. There was no history of hypopigmented patches or cutaneous lesions. There was no family history of leprosy or neuropathy. She was investigated with magnetic resonance imaging (MRI) of the spine and EMG/NCS three years before she was referred to our clinic. On examination, she was found to have a thickening of the right ulnar, median, and radial cutaneous nerves, and both posterior tibial nerves. Slit-skin smear was negative at multiple sites. Repeat EMG/NCS showed no sensory conduction in the right median, ulnar, radial, and both sural nerves, whereas amplitude and motor conduction velocity was reduced in the right median and both ulnar nerves. Laboratory investigations like hemogram, chest X-ray, urinalysis, liver function tests, renal function tests, and blood glucose levels were within normal limits. Finally, a biopsy of the left sural nerve was done which revealed three enlarged fascicles with a large number of infiltrating cells comprising lymphocytes, plasma cells, and macrophages in the endoneurium. Small clumps of acid-fast bacilli were seen in a good number of cells. A borderline lepromatous type of nerve lesion with evidence of type 1 reaction was diagnosed.

Case 2

A 38-year-old male, nondiabetic, was referred to our center for a slit-skin smear. The patient had a history of loss of sensation on the lateral aspect and heel of the left foot since three months. Past and family history was negative for neuropathy or leprosy. On examination, fine touch sensation was absent, whereas crude touch sensation was diminished in the left lower extremity. Left ulnar nerve, lateral peroneal, anterior tibial, and sural nerves were thickened. No hypopigmented patches were found. A diagnosis of leprosy was doubtful with such a short duration of complaints but EMG/NCS done before the patient was referred to us demonstrated left sural neuropathy. Therefore, a left sural nerve biopsy was done which showed granulomas comprising lymphocytes, macrophages, and epithelioid cells within and around fascicles. A borderline tuberculoid type of leprosy was diagnosed.

RESULTS

Of the 10 cases, six were males and four females, their age ranging from 11 to 63 years. Table 1 shows the demographics and details of individual cases. The histopathological findings of the nerve biopsy are shown in Table 2.

Table 1.

Demographic, clinical, and laboratory features of patients

Table 2.

Nerve biopsy findings

Figure 1 shows the main presenting complaints of the patients and the number of patients having the complaints.

Figure 1.

Presenting complaints of patients

Figure 2 shows the mode of diagnosis of leprosy in the patients. Clinically thickened nerves were found in nine patients out of ten. Slit-skin smear was negative in all cases except case 10 [Figures 3 and 4]. In one patient (illustrative case 1), the diagnosis was not done for six years despite several higher investigations like MRI and so on.

Figure 2.

Mode of diagnosis

Figure 3.

Ulcerative lesion on left forearm of patient 10

Figure 4.

Ulcerative lesion on right leg of patient 10

The diagnosis of leprosy could be confirmed in all the 10 cases, of which seven were diagnosed by nerve biopsy alone [Figures 5 and 6]. One case (case 9) was diagnosed clinically based on findings of thickening of the digital cutaneous nerve of the right hand (a rare finding) and extensive family history of leprosy.

Figure 5.

Histopathology of nerve biopsy of patient 3 (H and E, ×100)

Figure 6.

Borderline tuberculoid - midborderline type of disease in the nerve (H and E, ×400)

In one case, ultrasonography (USG) of the nerve was also done. [Figure 7].

Figure 7.

Ultrasonography findings of patient 1

DISCUSSION

Leprosy is a chronic infectious disease of the skin and nerves caused by Mycobacterium leprae.[2] It is an ancient disease which is now evolving in terms of its presentation and clinical scenarios. Most of the cases are still being diagnosed by classical presenting features such as hypopigmented, anesthetic patches, thickened nerves, and finding acid-fast bacilli on slit-skin smears and skin biopsies. However, cases are also being seen with predominantly neurological manifestations and also uncommon manifestations with none or few of the classical presentations. These conditions may be confused with other neurological disorders and the diagnosis of leprosy may be missed or delayed. Noordeen et al. has described pure neural leprosy as being characterized by neuropathic symptoms and thickened nerves with or without motor and sensory loss, in the absence of any cutaneous manifestation of leprosy.[3] Although the patients with no obvious skin lesions may be fewer in proportion than those with skin involvement (ranging from 4 to 16%), their detection and treatment are vital in preventing deformities,[4,5,6,7] and if the classical diagnostic criteria are used for diagnosis of leprosy, then many cases are bound to be overlooked.[8]

According to the latest statistics of the World Health Organization (WHO) on leprosy, India is still the largest contributor to the global patient load of leprosy.[1] With elimination of leprosy being the aim, early diagnosis and prompt therapy of the patients holds the key. Any delay in diagnosis and initiation of appropriate therapy would potentially lead to disastrous results and disabilities. As leprosy is not being detected by the usual methods in a subset of patients, higher diagnostic tests such as nerve biopsy have to be used on a routine basis for such patients.

Nerve biopsy has proved to be a more sensitive and revealing test than skin biopsy alone. The efficacy of nerve biopsy as a diagnostic tool, especially when skin lesions are absent, has been proved previously.[9,10,11,12] The usefulness of nerve biopsy over skin biopsy in the diagnosis of leprosy has also been demonstrated earlier.[13] In cases of mononeuropathy without a known etiology and without skin changes suggestive of leprosy, de Freitas et al. recommended superficial nerve biopsy as a mandatory procedure to confirm leprosy mainly in developing countries where it is prevalent.[14] Kaur et al., in their study of 108 neuritic leprosy patients, have documented that nearly two-thirds of the patients had a moderate to heavy bacterial load within the nerves despite all the patients having a negative skin smear.[15] Gabelle et al. have documented a case in France which presented with a slowly progressive asymmetric axonal sensory-motor neuropathy, where the diagnosis was made after a delay of eight years with the help of a nerve biopsy.[16]

Patients with complaints of predominantly neural manifestations such as tingling numbness, anesthesia, and nonhealing ulcers are more likely to visit neurologists and/or surgeons for treatment. Our study highlights that cases of neural leprosy are still very much present in the general population and therefore clinical suspicion of leprosy needs to be kept in mind. The diagnosis may be confirmed by a nerve biopsy, a relatively simple procedure with high diagnostic efficacy, which should be done promptly to establish the diagnosis and initiate the appropriate therapy without delay.

CONCLUSION

This study was done with the aim of bringing neural leprosy to the attention of neurologists, dermatologists, and leprologists alike. The interest in these cases was due to the fact that the diagnosis of leprosy on clinical grounds and routine testing was truly challenging and one had to resort to further investigations like nerve conduction studies and, nerve biopsies to confirm the diagnosis. India being an endemic region for leprosy, it is of paramount importance that differential diagnosis of leprosy be considered when faced with such cases in a busy outpatient neurology and dermatology setting. It is possible therefore, that many such patients with primary neurological complaints are likely to be seen and diagnosis either could be delayed or missed resulting in nerve damage and its consequences, if not thought of or investigated to confirm leprosy.