Type 2 Leprosy Reaction Mimicking Leukocytoclastic Vasculitis in a Postpartum Patient.

ABSTRACT: Leprosy is a disease caused by Mycobacterium leprae that, depending on a patient's baseline susceptibility and immune system function, can present in a wide variety of ways. The host's immune system response to the infection can be cell-mediated or humoral and can be further altered by changes in immune function or treatment. Depending on the time at which a skin biopsy is taken from affected areas, different inflammatory cell types are present, and the histopathology can mimic that of other infectious, autoimmune, or malignant entities, especially when the clinical information provided is vague. We present a case of a 24-year-old Micronesian woman who initially presented immediately postpartum with clinical and histopathological findings suggestive of urticarial vasculitis, but a subsequent biopsy resulted in a diagnosis of erythema nodosum leprosum reaction and borderline multibacillary leprosy. This case illustrates an unusual clinical and histological presentation of M. leprae and highlights the importance of clinical history.

[Association of borderline tuberculoid leprosy and tuberculosis: A case report and review of the literature]. / Association d'une lèpre borderline tuberculoïde et d'une tuberculose : un cas et revue de la littérature.

INTRODUCTION: In metropolitan France, nearly 20 new cases of leprosy are diagnosed each year. The incidence of tuberculosis in France is 8/100,000 inhabitants and there are very few accounts of association of these two mycobacteria. Herein we report a case of co-infection with borderline tuberculoid (BT) leprosy and disseminated tuberculosis diagnosed in metropolitan France. PATIENTS AND METHODS: A male subject presented with diffuse painless infiltrated erythematous plaques. The biopsy revealed perisudoral and perineural lymphohistiocytic epithelioid cell granuloma as well as acid-alcohol-fast bacilli on Ziehl staining. PCR was positive for Mycobacterium leprae, confirming the diagnosis of leprosy in the BT form. The staging examination revealed predominantly lymphocytic left pleural effusion, right-central necrotic adenopathy without histological granuloma, negative screening for BK, a positive QuantiFERON-TB™ test, and a positive intradermal tuberculin reaction. The clinical and radiological results militated in favour of disseminated tuberculosis. Combined therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) together with clofazimine resulted in regression of both cutaneous and extra-cutaneous lesions. This rare co-infection combines leprosy, often present for several years, and tuberculosis (usually pulmonary) of subsequent onset. The pathophysiological hypothesis is that of cross-immunity (with anti-TB immunity protecting against subsequent leprosy and vice versa), supported by the inverse correlation of the two levels of prevalence and by the protection afforded by tuberculosis vaccination. In most cases, treatment for TB and leprosy improves both diseases. Patients presenting leprosy should be screened for latent tuberculosis in order to avoid reactivation, particularly in cases where corticosteroid treatment is being given.

Th17 Response of Borderline-Lepromatous Leprosy Inhibits Rash Manifestation of Dapsone Hypersensitivity Syndrome: Case Report.

BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. OBJECTIVE: Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. METHODS: The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy. RESULTS: Laboratory testing was remarkable for leukocytosis with eosinophilia, atypical lymphocytosis, and elevated liver and canalicular enzymes. Immunohistopathology of the rash showed stronger expression of Th1 cytokines (IL1ß, TNFα, IFNγ, and iNOS), and limited expression of IL17, TGFb, IL4, and IL10. Whereas the hypochromic leprosy patches showed high expression of inflammatory cytokines IL1ß, TNFα, IFNγ, iNOS, and TGFß (Th1), and presented strong expression of IL17 and TGFß with no IL4 and IL10 expression, by the inflammatory infiltrate, characterizing a participation of Th17 response. CONCLUSION: Th17 response, coupled with the presence of subepidermal collagen band, seems to be directly related to the absence of DHS rash in these hypochromic leprosy patches.

A case report of erythroderma in a patient with borderline leprosy on reversal reaction: a result of the exacerbated reaction?

BACKGROUND: Erythroderma is characterized by erythema and scaling affecting more than 90% of the body surface area. Inflammatory, neoplastic and, more rarely, infectious diseases may culminate with erythroderma. Diagnosis of the underlying disorder is therefore crucial to institute the appropriate therapy. Leprosy is a chronic infectious disease that is endemic in Brazil. Here we present an unusual case of leprosy and reversal reaction causing erythroderma, and we discuss the underlying immunological mechanisms which could contribute to the generalized skin inflammation. CASE PRESENTATION: We report a case of a patient with reversal reaction (RR) in borderline borderline leprosy presenting with erythroderma and neural disabilities. Histopathology of the skin showed regular acanthosis and spongiosis in the epidermis and, in the dermis, compact epithelioid granulomas as well as grouped and isolated bacilli. This duality probably reflects the transition from an anergic/multibacillary state to a state of more effective immunity and bacillary control, typical of RR. Leprosy was successfully treated with WHO's multidrug therapy, plus prednisone for controlling the RR; the erythroderma resolved in parallel with this treatment. Immunologic studies showed in situ predominance of IFNγ + over IL-4+ lymphocytes and of IL-17+ over Foxp3+ lymphocytes, suggesting an exacerbated Th-1/Th-17 immunoreactivity and poor Th-2 and regulatory T-cell responses. Circulating Tregs were also diminished. We hypothesize that the flare-up of anti-mycobacteria immunoreactivity that underlies RR may have triggered the intense inflammatory skin lesions that culminated with erythroderma. CONCLUSIONS: This case report highlights the importance of thorough clinical examination of erythrodermic patients in search for its etiology and suggests that an intense and probably uncontrolled leprosy RR can culminate in the development of erythroderma.

Leprosy reactions in postelimination stage: the Bangladesh experience.

BACKGROUND: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. OBJECTIVES: To describe the pattern and prevalence of leprosy reactions in the postelimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. RESULTS: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. CONCLUSION: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services.

Leprosy - an overview of clinical features, diagnosis, and treatment.

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO-supported preventive measures and strategies play a key role in endemic areas.

Corticosteroid therapy in borderline tuberculoid leprosy patients co-infected with HIV undergoing reversal reaction: a clinical study.

Background: Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods: This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results: A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).

Bullous erythema nodosum leprosum manifesting in the post partum period with unusual features.

A 30 year old woman who presented with multiple numb patches on the body was initially diagnosed as borderline lepromatous leprosy and started on multidrug therapy for leprosy. She had an episode of Type 1 reaction during the fifth month of pregnancy. After delivery, she stopped therapy fearing harm to her child and developed an episode of Type 2 reaction. The reaction was unusual in that bullous lesions developed over previous leprosy patches which had initially become indurated, with associated neuritis. Histopathology revealed bullae with intense neutrophilic reaction and strong positivity for acid fast bacilli. There was no response to steroid therapy which was started for the reaction. Thalidomide had to be prescribed after stopping lactation by medical means. She responded dramatically to Thalidomide with regression of cutaneous lesions and neuritis. This patient is being reported as a very unusual manifestation of bullous erythema nodosum leprosum in the postpartum period responding dramatically to thalidomide.

A challenging case of borderline lepromatous leprosy non-responsive to WHO-MDT: exploring approaches beyond WHO-MDT.

Just as we prioritize personalized medicine for various other medical conditions, we should also include a neglected disease like leprosy, ensuring that patients receive the best care possible and improving their quality of life. Our case highlights the importance of instituting an alternate therapeutic regimen in a scenario where there is a lack of clinical response to multidrug therapy, even in the absence of documented drug resistance of the currently available molecular diagnostics. The search for the perfect regimen tailored for each individual leprosy patient should continue. Alternate anti-leprosy therapy is highly useful in cases with confirmed drug resistance or clinically non-responsive cases; however, their misuse should also be strictly avoided to prevent the development of resistance to them.

Case Report: Borderline Lepromatous Leprosy Therapy Complicated by Type 1 Leprosy Reaction and Adverse Reactions with Dapsone and Clofazimine.

Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.

Optic nerve involvement in a borderline lepromatous leprosy patient on multidrug therapy.

Amidst the plethora of ocular complications of leprosy, involvement of the posterior segment or optic nerve is extremely rare. The mechanism of optic neuritis in leprosy is poorly understood. A 47 year-old man presented with a single lesion suggestive of mid-borderline (BB) leprosy over left periorbital region; the histology showed borderline lepromatous (BL) leprosy with a BI of 3+. After initial improvement with WHO MDT-MB and prednisolone (40 mg/d) he developed sudden and painless diminished vision in the left eye, about 3 weeks later. His visual acuity was 6/9 in the left and 6/6 in the right eye, and there was left optic disc edema, hyperemia and blurred disc margins. Treatment with prednisolone (60 mg/d) along with WHO MDT-MB continued. A month later he returned with painless diminished vision in the other eye as well. Visual acuity was 6/6 in the right and 6/12 in the left eye, and there was right optic disc edema and left optic disc atrophy. CT of the head and MRI of the brain were normal. Inflammatory edema of the orbital connective tissue or other surrounding structures, or direct infiltration of vasa nervosa with resultant vascular occlusion leading to optic nerve ischemia, seems the most plausible explanation of optic nerve involvement in this case.

Childhood borderline lepromatous leprosy: a case report.

BACKGROUND: Leprosy in children is a strong indicator of the recent failure of leprosy control and disease transmission programs. For twenty-two years, leprosy has been declared `eliminated as a public health hazard,` yet new cases continue to emerge in endemic areas. The new case detection rate among the child population was recorded at 4.4 per million children. Because of their underdeveloped or neonatal immunity and exposure to intrafamilial contacts, children tend to be the most vulnerable population. CASE: We present a case of the borderline lepromatous type of leprosy in a 9-year-old Indonesian male patient with the chief complaint of three stiff fingers on his left hand that began four years ago and hypopigmented patches on the back and buttocks that began five years ago. In this case, there was a history of leprosy in his mother`s sister, who had died. Leprosy in the patient was suspected of possibly being transmitted from his mother`s sister who had intense contact with the patient. The results of bacteriological examination with Ziehl- Neelsen staining of tissue scrapings found acid-fast bacilli. He was treated with a multibacillary multidrug regimen for 12 months. Periodical observations after the patient received the treatment revealed no new spots on the patient`s skin, some of the previous hypopigmented patches seemed to fade, especially those on the back. CONCLUSIONS: In the absence of an effective vaccine, early diagnosis and treatment are critical in preventing disability and deformity and reducing the physical, psychosocial, and economic burden of the disease.

Trigeminal trophic syndrome complicating a case of borderline tuberculoid leprosy.

An example of trigeminal trophic syndrome presenting as ulceration of ala nasi in a case of borderline tuberculoid leprosy is reported. To the best of our knowledge, this is only the second case report of this manifestation in leprosy to be documented.

Is there a relation between hemicrania continua and leprosy?

The association of hemicrania continua and leprosy has been described in 2008. This relation can be causal or casual. Hemicrania continua is a strictly unilateral, moderate to severe, continuous, indomethacin-responsive primary headache with autonomic cranial symptoms and leprosy is an usual cause of peripheral neuropathy. Prevalence has fallen in the past years, but transmission continues and leprosy remains a public health problem. The objective of this study is to report one case of headache fulfilling the IHS criteria for HC, presented during the course of leprosy. A 61 years old woman started hypo and hiperpigmented lesions with impaired sensation to touch on right side of face (malar). She had biopsy in facial lesion and histopathology compatible with a borderline leprosy form. At the same time, she reported new headaches, daily and continuous, without pain-free periods, unilateral (which were located in the same side of the leprosy lesion in face), throbbing and severe (VAS = 8) with ipsilateral conjuntival injection and lacrimation that improved with indomethacin. We hypothesize that the local injury on the face of this patient predisposes a mechanism of central sensitization, resulting in trigeminal autonomic cephalgia. Relation between trigemino-autonomic cephalalgias and leprosy provides insights into craniofacial pain mechanisms.

Diagnosing and treating leprosy in a non-endemic setting in a national centre, London, United Kingdom 1995-2018.

BACKGROUND: Leprosy is rare in the United Kingdom (UK), but migration from endemic countries results in new cases being diagnosed each year. We documented the clinical presentation of leprosy in a non-endemic setting. METHODS: Demographic and clinical data on all new cases of leprosy managed in the Leprosy Clinic at the Hospital for Tropical Diseases, London between 1995 and 2018 were analysed. RESULTS: 157 individuals with a median age of 34 (range 13-85) years were included. 67.5% were male. Patients came from 34 different countries and most contracted leprosy before migrating to the UK. Eighty-two (51.6%) acquired the infection in India, Sri Lanka, Bangladesh, Nepal and Pakistan. 30 patients (19.1%) acquired leprosy in Africa, including 11 from Nigeria. Seven patients were born in Europe; three acquired their leprosy infection in Africa, three in South East Asia, and one in Europe. The mean interval between arrival in the UK and symptom onset was 5.87 years (SD 10.33), the longest time to diagnosis was 20 years. Borderline tuberculoid leprosy (n = 71, 42.0%), and lepromatous leprosy (n =, 53 33.1%) were the commonest Ridley Jopling types. Dermatologists were the specialists diagnosing leprosy most often. Individuals were treated with World Health Organization recommended drug regimens (rifampicin, dapsone and clofazimine). CONCLUSION: Leprosy is not a disease of travellers but develops after residence in an leprosy endemic area. The number of individuals from a leprosy endemic country reflect both the leprosy prevalence and the migration rates to the United Kingdom. There are challenges in diagnosing leprosy in non-endemic areas and clinicians need to recognise the symptoms and signs of leprosy.

Cutaneous ulceration as a presenting feature of type 1 lepra reaction: A case report.

Reactions in leprosy represent sudden shift in the immunological response and are seen in 11-25% of affected patients. It can be seen before, during or after the completion of multidrug therapy (MDT).1 Two types of reactions are recognized; Type 1 reaction (T1R), seen in borderline leprosy, affecting mainly skin and nerves; type 2 reaction (T2R) or erythema nodosum leprosum (ENL), seen in lepromatous leprosy, characterized by systemic features in addition to cutaneous lesions. Trophic ulcers and ulcerating ENL are well known entities while cutaneous ulceration in T1R is extremely rare; we describe an immune-competent woman with cutaneous ulceration as a presenting feature to highlight the need to recognize this entity at the earliest opportunity.

Oral lesion in leprosy: borderline tuberculoid diagnosis based on detection of Mycobacterium leprae DNA by qPCR.

Oral lesions are rarely reported in paucibacillary forms of leprosy. We report here a case with an erythematous hyposensitive lesion in the palate and no skin lesions. In addition to routine tests, biopsies of the lesion in the palate and of clinically normal surrounding areas were performed and subjected to real-time PCR for detection of Mycobacterium leprae DNA. The biopsy of the oral lesion was positive for bacilli DNA, followed by positive serum anti-PGL-1 and Mitsuda test, but with negative histopathology. The patient was diagnosed with a borderline tuberculoid form. After multidrug therapy the lesion had significantly regressed and the bacilli DNA detection in the former lesion was negative. The bacilli DNA detection in an oral lesion by real-time PCR not only improved leprosy diagnosis, but also helped in the classification of clinical form, and in the establishment of the appropriate therapeutic regime.

Secondary leprosy infection in a patient with psoriasis during treatment with infliximab.

Tumor necrosis factor α antagonists are proven to be effective for the treatment of chronic inflammatory conditions, such as psoriasis. A major concern for patients is the risk of acquiring granulomatous infectious diseases caused by the immunosuppressive effects of the drugs. We report a 60-year-old man with psoriasis who underwent infliximab treatment for 2 years and developed secondary leprosy, presenting extensive erythematous and infiltrated plaques on the trunk and limbs with loss of sensitivity (thermal, pain and tactile). The skin lesion biopsy showed perivascular epithelioid granulomas, nodular dermal aggregates of foamy macrophages and bundles of acid-fast bacilli. The clinical picture associated with histopathologic evaluation suggested borderline lepromatous leprosy. Before infliximab treatment, the patient had a positive tuberculin skin test and underwent chemoprophylaxis treatment for latent tuberculosis. Although the tuberculin reactivity suggests a strong correlation with a latent Mycobacterium tuberculosis infection, the possibility of infections by other mycobacteria, such as Mycobacterium leprae, should not be discarded.