Skin lesions in histoplasmosis

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.

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?

In the history of modern medicine, in terms of physical stigma, leprosy is a predominant disease and the probable reason is that the disease, even in the lepromatous spectrum, does not account for mortality but only for the visible deformity which proves to be a major cause of life-long stigamtization1. Stigma has been defined by Goffman2 as ‘an attribute that is deeply discrediting, and the stigmatized individual is one who is not accepted and not accorded the respect and regard of his peers; one who is disqualified from full social acceptances’. Stigma was sub-divided into three main groups, with the physical deformity of face being the predominant. This definition is appropriately relevant to leprosy where the oft depicted facial morphology of the neglected lepromatous patient is the universal depictive connotation of leprosy. The other deformities including facial plaque of the non-lepromatous patient (especially if in reaction), facial palsy, claw hand deformity, foot-drop or the hypopigmented macules which are conspicuous on dark skin. The perception ingrained in the general conscience is such that leprosy in all its varied forms is infectious and its carriers worthy of being discriminated.

Leprosy stigma & the relevance of emergent therapeutic options

Bullous pemphigoid (BP) is an autoimmune blistering skin disease. Current treatment strategies are limited by their efficacy and/or side effect profile and the need for safer and effective alternatives is undeniable. We aimed to conduct a systematic review focusing on the efficacy and safety of omalizumab in BP patients. Embase, PubMed, Cochrane, and clinicaltrials.gov were searched for English and French articles published from inception to July 1, 2021, using search terms “omalizumab” OR “Xolair” OR “IGE025” OR “olizumab” AND “bullous pemphigoid.” Screening and data extraction was performed by two raters independently. The primary outcome was complete response (CR), and secondary outcomes were partial response (PR), flare-ups, adverse events/vital status. In total, 22 articles were included, with a total of 56 patients. All patients had a refractory BP with mean disease duration of 13.5 ± 20.2 months (Standard Deviation (SD)) and failed 3.1 ± 1.6 therapies and many remained corticosteroids dependent. Overall, 87.5% of patients responded to treatment (55.4% CR and 32.1% PR), 7.1% discontinued the protocol and only 5.4% were non responders. A third of patients were able to discontinue all other therapies and most others were able to discontinue or taper systemic corticosteroids to <10 mg daily. Flare-ups occurred in 57.7% of patients upon discontinuation of omalizumab and/or steroid tapering, most patients recaptured response thereafter. Omalizumab was well tolerated by most patients. Omalizumab appears to be a promising treatment for BP with a good response rate and safety profile. However, several limitations were identified in current literature, and highlight the need for randomized controlled trials of omalizumab in BP.

Omalizumab for the Treatment of Bullous Pemphigoid: A Systematic Review of Efficacy and Safety

The role of IgE autoantibodies has been demonstrated in the pathogenesis of bullous pemphigoid for many years. Recently, omalizumab (OMZ), a humanized monoclonal anti-IgE antibody that depletes total serum IgE, has been used off-label in a few case series of bullous pemphigoids demonstrating a rapid efficacy and allowing significant improvements or complete remission as add-on therapy in first-line treatment-resistant patients. Herein, we report the largest retrospective study to evaluate OMZ effectiveness in patients with subepidermal autoimmune blistering diseases. Our series included 13 patients from a single center with bullous pemphigoid or mucous membrane pemphigoid, of whom 7 had mucous membrane involvement. OMZ was added to the unchanged immunosuppressive therapies. Detailed clinical and immunological data during the first year were collected, notably for specific anti-BP180-NC16A IgE and IgG, and the median total follow-up was 30 months (range: 3–81). Our series demonstrated that OMZ induced a significant improvement in pruritus, urticarial score, and daily blister count on day 15, allowing disease control to be achieved in a 1-month median time and complete remission (CR) in a 3-month median time in 85% of these patients previously in therapeutic impasse. At the end of the follow-up, 31% of patients achieved CR on minimal therapy after OMZ weaning without relapses, and 54% achieved CR on OMZ continuation with a minimal dose of concomitant treatment. Two patients experienced therapeutic failure (15%). At baseline, clinical variables reflecting activity were significantly positively correlated with eosinophil blood count, total IgE serum level, specific anti-BP180 IgE and IgG. While baseline anti-BP180 IgG and specific anti-BP180 IgE were significantly positively correlated, only the two patients who experienced a therapeutic failure with OMZ did not fit with this correlation, demonstrating elevated levels of anti-BP180 IgG with no measurable BP180-specific IgE. Follow-up of immunological variables demonstrated a rapid decrease of eosinophilia towards normalization, whereas a slower decline towards negativation was observed over 1 year for anti-BP180 IgG and anti BP180 IgE in patients who responded to OMZ. This case series demonstrated that OMZ is a rapidly effective biologic therapy for refractory bullous pemphigoid and mucous membrane pemphigoid, permitting rapid disease control and reduction of concomitant therapeutics.

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Rapid Disease Control in First-Line Therapy-Resistant Mucous Membrane Pemphigoid and Bullous Pemphigoid with Omalizumab as Add-On Therapy: A Case Series Of 13 Patients

While Type 1 reaction in Hansen's disease is commonly encountered, the triggers and reasons for its persistence are not well understood even though the immunological milieu and cytokine interplay have been studied. Herein, we present a case of Type 1 downgrading reaction in which multidrug resistance was the probable cause of steroid-nonresponsiveness and which responded promptly on starting alternate antileprosy treatment.

Multidrug resistance as a cause of steroid-nonresponsive downgrading type I reaction in Hansen's disease.

Bullous pemphigoid (BP) is an autoimmune disorder known to be mediated by immunoglobulin G (IgG) autoantibodies. The role of immunoglobulin E (IgE) antibodies is being investigated as their presence has been described in severe cases. Herein, we report a patient of BP who was refractory to most conventional agents and developed hypotension after rituximab but achieved lasting remission after a single dose of the anti-IgE monoclonal antibody omalizumab.

Complete remission in a patient with treatment refractory bullous pemphigoid after a single dose of omalizumab

While Type 1 reaction is seen in leprosy patients, in up to 30% of patients, late reaction is uncommon and usually is seen in the first two years of release from treatment (RFT). It is believed tha...

https://journals.sagepub.com/doi/pdf/10.1177/0049475519884421

Late reversal reaction with resistant Mycobacterium leprae : an emerging paradigm.

Reactions in leprosy are acute inflammatory episodes that can be classified as type I or type II. Recognition and timely management of these patients is critical to avoid permanent disability. We p...

An uncommon variant of erythema nodosum leprosum responding well to methotrexate: Report of two cases.

Histoplasmosis is a systemic fungal disease that may be presented with a variety of clinical manifestations, usually as an opportunistic infection in immunocompromised individuals. We present an HIV seropositive patient with a large fleshy growth causing left-sided nasal obstruction, as an unusual presentation. The lesions shrunk dramatically and almost completely on intravenous amphotericin-B lipid complex (ABLC) given for 2 weeks followed by long-term oral itraconazole.

Diksha Agrawal

Papers

Multidrug resistance as a cause of steroid-nonresponsive downgrading type I reaction in Hansen's disease.

Complete remission in a patient with treatment refractory bullous pemphigoid after a single dose of omalizumab

Late reversal reaction with resistant Mycobacterium leprae : an emerging paradigm.

An uncommon variant of erythema nodosum leprosum responding well to methotrexate: Report of two cases.

Cutaneous Histoplasmosis: An Unusual Presentation with Nasal Obstruction.