Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug-resistance testing in leprosy?

BACKGROUND: Leprosy relapse/recurrence is a serious concern particularly in a leprosy-endemic nation such as India. It is believed that bacilli persisting even after multidrug therapy can cause relapse; recently, however, drug resistance as a cause for recurrences and chronic erythema nodosum leprosum (ENL) has been speculated. AIM: To study drug-resistance patterns in cases of leprosy relapse and chronic/recurrent (c/r)ENL. METHODS: This cross-sectional study conducted over a period of 1 year included patients diagnosed as having leprosy relapse and those with c/rENL. Skin biopsy specimens were examined by conventional PCR for resistance testing for rifampicin, dapsone and ofloxacin, respectively targeting the rpoB, folP and gyrA genes of Mycobacterium leprae. RESULTS: In total, 61 patients (25 smear-negative) were included in the study. Of these, 37 were diagnosed as having leprosy relapse and 24 as having c/rENL. Drug resistance to at least one drug was identified in 10 cases (16.4%). Rates of drug resistance were 5.4% (2 of 37) for dapsone, 10.8% (4 of 37) for rifampicin and 2.7% (1 of 37) for ofloxacin among cases of relapse, whereas it was 12.5% (3 of 24) and 8.3% (2 of 24) for dapsone and rifampicin respectively among those with c/rENL. Multidrug resistance was seen in 3.3% patients (2 of 61). CONCLUSION: Drug-resistance rate among those with c/rENL was almost equalled that of relapse. Smear-negative leprosy relapse cases also had resistance to bactericidal drugs. These findings call for modifications in criteria for testing under leprosy drug-resistance surveillance and all cases of relapse and those with recalcitrant c/rENL should be tested.

Apremilast in chronic recalcitrant erythema nodosum leprosum: a report of two cases.

Erythema nodosum leprosum (ENL) is a severe immune reaction commonly encountered as a complication in patients with multibacillary leprosy. Management of chronic ENL in leprosy is challenging and necessitates the use of systemic immunosuppressants, including corticosteroids and thalidomide. No single drug is universally effective and most current therapeutic agents carry a significant risk of systemic toxicity. Apremilast is an orally effective phosphodiesterase-4 inhibitor with a potent immunomodulatory action and is clinically effective in inflammatory conditions like chronic plaque psoriasis. We report two patients with poorly controlled chronic ENL, despite the use of multiple therapeutic agents. Both patients demonstrated significant clinical improvement with apremilast, without any adverse effects, thereby suggesting its potential as a novel therapeutic option in chronic ENL. What's already known about this topic? Erythema nodosum leprosum (ENL) is an immune-mediated reaction in patients with multibacillary leprosy, with chronicity and recurrences frequently reported. Management of chronic ENL requires systemic immunosuppressants like corticosteroids, which may not be universally effective and carry a risk of serious toxicity. Apremilast is an oral immunomodulator with good efficacy in inflammatory conditions like chronic plaque psoriasis. What does this study? Apremilast may be an effective therapeutic agent in patients with chronic ENL.

Dermatoscopy in leprosy and its correlation with clinical spectrum and histopathology: a prospective observational study.

BACKGROUND: Leprosy, a chronic granulomatous infection has varied clinical presentations spanning across different spectrums. The scope of dermatoscopy is vast and has been studied for other granulomatous disorders like sarcoidosis. OBJECTIVES: The objective of this study was to describe the dermatoscopic features of the entire spectrum of leprosy and to correlate with clinical and histopathological findings. METHODS: This was a prospective observational study of treatment naïve leprosy patients over a period of 1 year. The study patients were categorized as per Ridley-Jopling classification based on clinical, slit skin smear and histopathological findings. Most representative lesions were photographed, evaluated by dermatoscopy and were biopsied. RESULTS: A total of 30 patients (21 males and 9 females) were recruited; 2 cases of tuberculoid leprosy, 12 cases of borderline tuberculoid (3 with type 1 reaction), 8 cases of borderline lepromatous, 6 cases of lepromatous leprosy (3 with type 2 reaction) and 2 cases of Histoid leprosy. The dermatoscopic featues consistently seen were yellowish orange areas and vascular structures like linear branching vessels and crown vessels correlating with the presence of dermal granulomas and dilated vessels. Broken pigment network, white chrysalis like areas were seen in addition. Tuberculoid spectrum also had absence of or diminished hair follicles and eccrine duct openings correlating with presence of peri-appendageal granuloma and appendageal destruction. Scaling and follicular plugs were other features in lesions of type 1 reaction. CONCLUSION: Yellowish-orange areas and vascular structures are the common dermatoscopic features of leprosy. Broken pigment network and paucity of appendageal structures are additional specific features.

Histoid leprosy: a retrospective study of 40 cases from India.

BACKGROUND: Rare variants of leprosy pose a diagnostic challenge even to astute clinicians and histoid leprosy is one such form of disease with unique clinical and histopathological features. There are very few large series on this entity, mainly reported from India. OBJECTIVES: To study the epidemiological and clinical characteristics of patients with histoid leprosy. METHODS: We undertook this retrospective study including patients registered with the leprosy clinic of our tertiary care referral centre from January 1991 to December 2006. Data regarding demographic details, clinical features, treatment, complications and course following treatment were extracted from the records of the leprosy clinic. RESULTS: The incidence of histoid leprosy among the registered patients of our clinic was 1.8% (40 of 2150). There was a significant male preponderance with a male/female ratio of 5.7 : 1. The anatomical areas of involvement were thighs/buttocks (67.5%), arms (62.5%), back (52.5%), face (47.5%), forearms (47.5%) and legs (35%) in descending order of frequency. This variety of leprosy was found most commonly in patients with a primary diagnosis of lepromatous leprosy (40%). De novo histoid lesions, i.e. lesions of histoid leprosy developing without evidence of lesions of other types of leprosy in the Ridley-Jopling classification, appeared in 12.5% of patients only. Only three patients had received antileprosy treatment before presentation. Episodes of erythema nodosum leprosum (ENL) had occurred in 40% of patients, although only one patient manifested ENL after the diagnosis of histoid leprosy. The disease responded satisfactorily to the respective World Health Organization multidrug therapy regimens in all except in one patient who relapsed with borderline lepromatous leprosy. CONCLUSIONS: As the bacillary load is very high in these patients, they can form a potential reservoir of the infection in the community especially in the postleprosy elimination era. Contrary to the earlier belief in the dapsone era, most of our patients manifested disease without any history of inadequate or incomplete antileprosy therapy.

Leprosy and herpes zoster; an association or dissociation?

Nerve involvement is common to the pathogenesis of both leprosy and herpes zoster. We report two cases of borderline leprosy in which the skin lesions characteristically spared the healed zoster scar. Possible mechanisms and relationship are discussed.