MicroRNAs correlate with bacillary index and genes associated to cell death processes in leprosy.

Mycobacterium leprae infects skin and peripheral nerves causing a broad of clinical forms. MicroRNAs (miRNAs) control immune mechanisms such as apoptosis, autophagy as well as to target genes leading to abnormal proliferation, metastasis, and invasion of cells. Herein we evaluated miRNAs expression for leprosy phenotypes in biopsies obtained from patients with and without reactions. We also correlated those miRNAs with both, bacillary index (BI) and genes involved in the micobacteria elimination process. Our results show a significant increase in the miR-125a-3p expression in paucibacillary (PB) patients vs multibacillary (MB) subjects (p = 0.007) and vs reversal reactions (RR) (p = 0.005), respectively. Likewise, there was a higher expression of miR-125a-3p in patients with erythema nodosum leprosum (ENL) vs MB without reactions (p = 0.002). Furthermore, there was a positive correlation between miR-125a-3p, miR-146b-5p and miR-132-5p expression and BI in patients with RR and ENL. These miRNAS were also correlated with genes such as ATG12 (miR-125a-3p), TNFRSF10A (miR-146b-5p), PARK2, CFLAR and STX7 (miR-132-5p). All together we underpin a role for these miRNAs in leprosy pathogenesis, implicating mechanisms such as apoptosis and autophagy in skin. The miR-125a-3p might have a distinct role associated with PB phenotype and ENL in MB patients.

Skin and Mucous Membrane Eruptions Associated with Chlamydophila Pneumoniae Respiratory Infections: Literature Review.

BACKGROUND: Mycoplasma pneumoniae pneumonia is sometimes associated with skin or mucous membrane eruptions. Available reviews do not address the association of Chlamydophila pneumoniae pneumonia with skin eruptions. We therefore conducted a systematic review of the literature addressing this issue. The National Library of Medicine, Excerpta Medica, and Web of Science databases were employed. SUMMARY: In two reports, skin lesions and especially urticaria were more common (p < 0.05) in atypical pneumonia caused by C. pneumoniae as compared with M. pneumoniae. We found 47 patients (<18 years, n = 16; ≥18 years, n = 31) affected by a C. pneumoniae atypical pneumonia, which was associated with erythema nodosum, erythema multiforme minus, erythema multiforme majus, isolated mucositis, or cutaneous vasculitis. We also found the case of a boy with C. pneumoniae pneumonia and acute generalized exanthematous pustulosis. We did not find any case of C. pneumoniae respiratory infection associated with either Gianotti-Crosti syndrome, pityriasis lichenoides et varioliformis acuta Mucha-Habermann, or varicella-like skin eruptions.

A dissimulate presentation of histoid Hansen's disease in the form of erythema nodosum leprosum.

Hansen's disease is a chronic infectious granulomatous disease with varied clinical presentation. Histoid Hansen's disease is an important emerging lepromatous subset of Hansen's disease known to mimic varied dermatoses. Occurrence of reactions, especially erythema nodosum leprosum (ENL), is rare in this form of leprosy. We report a case of Histoid Hansen's disease with initial presentation of ENL while undergoing management for infertility.

Leprosy manifesting with type 2 leprae reaction in a patient presenting with chronic fever: A case report.

Leprosy is a chronic granulomatous disease involving the skin and nerves, leading to a debilitating condition. Leprosy has been controlled in most parts of the world; therefore physicians are not very well versed in the recognition, management and assessment of this disease. The protean manifestations of leprosy often lead to delays in diagnosis and increase the morbidity. We present a case of a 33-year-old male with fever, lymphadenopathy, nodular skin lesions, uveitis and arthritis. Lymphnode, bonemarrow and skin biopsy revealed 3+ AFB smear with negative AFB cultures, leading to the diagnosis of leprosy. The course of illness was complicated by flare of Erythema Nodosum Leprosum (ENL).

Effectiveness of the retreatment of patients with multibacillary leprosy and episodes of erythema nodosum leprosum and/or persistent neuritis: a single-center experience

Abstract: Background: Erythema nodosum leprosum may appear before, during or after treatment of leprosy and is one of the main factors for nerve damage in patients. When it occurs or continues to occur after treatment, it may indicate disease recurrence and a new treatment may be instituted again. Objective: To evaluate the retreatment of patients with multibacillary leprosy who underwent standard treatment with multidrug therapy, but developed or continued to present reactions of erythema nodosum leprosum and/or neuritis 3-5 years after its end. Method: For this objective, a new treatment was performed in 29 patients with multibacillary leprosy who maintained episodes of erythema nodosum and/or neuritis 3-5 years after conventional treatment. Results: In general, we observed that 27 (93.10%) had no more new episodes after a follow up period of eight months to five years. In five of these patients the reason for the retreatment was the occurrence of difficult-to-control neuritis, and that has ceased to occur in all of them. Study limitations: Small number of patients.. Conclusion: In the cases observed, retreatment was an effective measure to prevent the occurrence of erythema nodosum leprosum and/or persistent neuritis.

Bullous Erythema Nodosum Leprosum as the First Manifestation of Multibacillary Leprosy: A Rare Phenomenon.

Erythema nodosum leprosum (ENL) may uncommonly present before treatment in patients with multibacillary leprosy. Atypical manifestations are known in ENL and may be clinically misleading. Such wide variations in the clinical presentation of leprosy in reaction make histopathology an important tool for supporting clinical diagnosis. We report bullous ENL presenting as the first manifestation of leprosy in a 30-year-old Indian man diagnosed using histopathology.

Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.

Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.

[Erythema nodosum due to tinea]. / L'érythème noueux, une complication des teignes à Trichophyton mentagrophytes.

UNLABELLED: Erythema nodosum (EN) is the most common clinical and pathological variant of panniculitis. A Celsus kerion is an inflammatory and suppurative tinea of the scalp. We report on a rare case of EN secondary to a kerion of the scalp. OBSERVATION: A 9-year-old child without a notable medical history, had a squamous plaque of the vertex for 15 days, which became painful and purulent. Five days after the plaque appeared, he presented with painful, hot, erythematous lesions symmetrically on the extensor surfaces of the legs and forearms. A medical examination found a fever of 38.5°C, a squamous purulent and crusty plate of the vertex (6/5cm) with pustules and a few hairs cut short, and symmetrical painful erythematous hot nodules on the anterior surfaces of the two legs and forearms. A mycological sample of the crusts of the scalp lesion confirmed the presence of Trichophyton mentagrophytes. A bacteriological sample was not taken, and a skin biopsy confirmed the diagnosis of EN. The results of other paraclinical investigations were normal. The diagnosis of EN secondary to an inflammatory scalp tinea was established, and our patient was prescribed an orally and locally administered antimycotic, rest, and elevation of the limbs. DISCUSSION: EN is an acute nodular hypodermitis considered a nonspecific hypersensitive reaction to various allergens. Rarely, it can occur secondary to a fungal infection of the scalp such as a kerion or even secondary to the antifungal treatment of this tinea. EN secondary to a kerion of the scalp before the beginning of antifungal treatment has been reported in the literature, with a spontaneous improvement of the EN after treatment of the tinea.

Unusual Presentation of Necrotic Erythema Nodosum Leprosum on Scalp: A Case Report.

Lepra reactions are acute episodes occurring during the disease process of leprosy and are of 2 types: type 1 or reversal reaction and type 2 reaction or erythema odosumleprosum (ENL). In the episodes of lepra reaction several parts are affected including face and extremities like oral cavity. In the present case report we reported a rare case of lepromatous leprosy with necrotic ENL involving scalp apart from the usual sites. A 58 year old married male presented to us with complaints of spontaneous onset, recurrent eruption of multiple reddish raised painful lesions. Biopsy from the infiltrated skin over the back showed atrophic epidermis, free Grenz zone, diffuse and periadnexal macrophage granulomas with predominant mononuclear infiltrate, appandageal atrophy, fibrosis around the neural structures and leukocytoclastic vasculitis. Fites stain showed strong positivity for M. leprae. His routine blood investigations showed anemia (Hb = 7.8 gm%), neutrophil leukocytosis (TLC = 17,600, DLC = P66L28M4E2) and raised ESR (80 mm in the first hour). These bullous and necrotic lesions in leprosy may be a manifestation of severe type II reactions in patients with very high bacillary load.

A study on histological features of lepra reactions in patients attending the Dermatology Department of the Government Medical College, Calicut, Kerala, India.

OBJECTIVES: 1. To study and compare the clinical and histological features of Type 1 and Type 2 lepra reactions. 2. To document the histological patterns of Type 1 and Type 2 lepra reactions observed in the study population. DESIGN: Two year cross sectional study. Patients attending the outpatient department of our tertiary care hospital, during the 2 year study period with clinical evidence of Type 1 (T1R) or Type 2 (T2R) lepra reactions were included in this study after obtaining written informed consent. During this period 34 T1R patients and 14 T2R patients attended our hospital. Biopsies were taken from reacting skin lesions of all patients and histological features were studied. RESULTS: Dermal or intragranuloma oedema was evident in 50% of T1R patients and all of them had clinically severe reactions. The T1R patients showed three different histological patterns--pgrading reactions, downgrading reactions and reactions without upgrading or downgrading. Among T2R patients 8/14 showed neutrophil infiltration histologically, 5/14 showed no histological evidence of neutrophil infiltration and only one patient had features of neutrphilic vasculitis. Dermal oedema was seen in 11/14 cases. CONCLUSIONS: Histology revealing dermal or intragranuloma oedema on a background of leprosy granuloma favours the diagnosis of lepra reaction. A careful analysis of subtle variations in the cells constituting the granuloma may aid in differentiating between upgrading T1R, downgrading T1R or T1R without upgrading or downgrading. Histology can also be useful in distinguishing T2R from T1R, in the absence of typical erythema nodosum leprosum (ENL) lesions. Neutrophils are the major inflammatory cells in the former where as lymphocytes or macrophages predominate in the latter. We recommend that histopathological analysis should form an integral part of the evaluation of all lepra reactions.

Histoplasmosis and subcutaneous nodules in a kidney transplant recipient: erythema nodosum versus fungal panniculitis.

Erythema nodosum (EN)-like lesions are a rare occurrence after solid organ transplantation. Differential diagnosis includes infective panniculitis, which can be a feature of progressive disseminated histoplasmosis (PDH), an uncommon but severe form affecting primarily immunocompromised hosts. We report on a fatal case of PDH, which presented as fungal panniculitis masquerading as EN in a renal allograft recipient 25 years after transplantation. We discuss the clinical, histopathological, and microbiological characteristics of this rare complication, with focus on its distinction from EN. This case emphasizes the central role of biopsy in transplant recipients presenting with cutaneous lesions, and the importance of clinicopathologic correlation and complementary microbiological investigations.

Treated Whipple disease with erythema nodosum leprosum-like lesions: cutaneous PAS-positive macrophages slowly decrease with time and are associated with lymphangiectases: a case report.

Pathologically, Whipple disease (WD) is characterized by the accumulation of myriad macrophages parasitized by Tropheryma whipplei (TW) bacilli denoted by periodic acid-Schiff (PAS) positivity. These PAS+ macrophages are typically found in the duodenum associated with lymphangiectasia. Recently, we reported the presence of PAS+ macrophages and free TW in erythema nodosum leprosum (ENL)-like lesions and normal skin in a patient with WD who suffered from the immune reconstitution inflammatory syndrome (IRIS). We extend that report by describing the clinical and pathologic findings over 5 years of follow-up. First, the IRIS gradually diminished and abated over 18-month time. Second, at no point did WD recur, and all duodenal and skin biopsies tested by polymerase chain reaction were negative for TW DNA. Third, PAS+ macrophages were identified in 26 of 27 skin biopsies (96%) and decreased along with free TW over time. Fourth, ENL-like lesions had significantly greater numbers of PAS+ macrophages than normal skin. Moreover, normal abdominal skin (region of ENL-like lesions) had greater PAS+ counts than arm skin (not a site of IRIS). Last, lymphangiectases, a histologic sign of lymphostasis, was found in all skin biopsies. Overall, these findings implicate bacillary burden as a factor in the immune tolerance to live TW in active WD and the initiation of ENL-like nodules against dead/nonreplicative TW in treated WD. In addition, poor lymphatic drainage is likely responsible for the gradual clearance of TW from the skin and the impaired delayed-type hypersensitivity reaction (absence of activated macrophages) against TW found in WD, presumptively due to reduced/absent immune cell trafficking necessary for lymphocyte-macrophage interactions and induction of adaptive immunity.

[Bilateral inguinal lymphadenopathy and erythema nodosum: an uncommon presentation of cat scratch disease]. / Adénopathies inguinales bilatérales et érythème noueux: une présentation originale de la maladie des griffes du chat.

Cat scratch disease is usually revealed by a proximal lymphadenopathy related to the inoculation site. We report a 22-year-old female who presented with erythema nodosum and bilateral inguinal lymphadenopathy. Serologic test and lymph node PCR detection for Bartonella henselae were negative. Nevertheless, the patient received doxycycline and clinical manifestations rapidly resolved. A follow-up detection of IgM and IgG against Bartonella henselae performed 1 month later was positive. This case report illustrates an original presentation of cat scratch disease and reminds us the lack of sensitivity of laboratory investigations.

Some unusual type 2 reactions in leprosy.

BACKGROUND: Type 2 reactions with lepromatous leprosy (LL) not occurring during multi-drug therapy (MDT) have been reported. METHODS: Three patients have been described, each representing a prototype, the first presenting as bullous erythema nodosum leprosum (ENL), second with ENL erupting after treatment for co-existing pulmonary tuberculosis and resembling immune reconstitution inflammatory syndrome, and a third patient with recurrent Sweets-syndrome like presentation who had taken incomplete MDT in the past for leprosy. In all, the diagnosis was established by demonstration of acid-fast bacilli (AFB) on slit-skin smears (SSS) and histopathology. RESULTS & CONCLUSION: The fact that reactions can occur in patients with clinically inapparent LL, who are more likely to present in general hospitals, has been reemphasized to enhance awareness among physicians. First presentation of leprosy as ENL is probably precipitated by common antibiotics taken for other illnesses. Since reactional episodes can occur before, during and after MDT for leprosy and the clinical picture is not specific to any of them, it is important to ascertain the status of anti-leprosy therapy during these episodes and treat them accordingly.

Concomitant lucio phenomenon and erythema nodosum in a leprosy patient: clues for their distinct pathogeneses.

Lepromatous leprosy patients may develop necrotic lesions, usually in the context of Lucio phenomenon (LP) or severe erythema nodosum (EN). The clinical and histopathological characteristics of the necrotic manifestations of both entities may eventually be confounded. We describe a patient with lepromatous leprosy who developed, since the 4th month of her first pregnancy, recurrent necrotic lesions in lower limbs, which, at the postpartum, worsened and led to partial destruction of ears and nose. In addition, she referred painful nodes on upper limbs since 1 year before pregnancy and intermittent swelling and tenderness of the ankles, which together with a right tibial and ulnar neuritis led to the diagnosis of, erythema nodosum leprosum (ENL). The histopathology of a biopsy of the upper limb (ENL) revealed a dermal-hypodermal inflammation with vasculitis and vascular lumen narrowing, whereas biopsy of the lower limb (LP) revealed small vessels with fibrin thrombi on the superficial layer of the dermis without inflammatory infiltrate and no evidence of vasculitis. Thus, besides having several different clinical features, LP and ENL result from different pathogenetic mechanisms. The histopathological and clinical features distinguishing both entities are proposed. This distinction is important because decrease in bacillary load through multidrug therapy is the main target in LP, whereas in ENL, concomitant reduction of the reaction by means of thalidomide or high-dose steroids is recommended.

Brucella melitensis presenting as erythema nodosum-like lesions.

Brucellosis is a chronic granulomatous zoonosis with protean manifestations. Cutaneous involvement in Brucellosis is a relatively rare phenomenon. We describe a case of Brucella melitensis infection presenting with erythema nodosum like skin lesions involving palms and soles in a 70 years old lady.

Presentación clínica de la tuberculosis infantil / Clinical presentation of childhood tuberculosis

Establecer el diagnóstico de tuberculosis (TBC) en niños no es fácil. Muchas de sus manifestaciones son inespecíficas, por lo que requiere alto índice de sospecha. Mas aún, en nuestro medio, la TBC es una condición infrecuente. Este artículo brinda una revisión en torno a los conceptos contacto y primoinfección, ilustrando de manera breve algunos escenarios clínicos como TBC pulmonar primaria progresiva, TBC ósea y eritema nodoso de nuestra práctica diaria.

The ever-expanding association between rheumatologic diseases and tuberculosis.

We summarized most of the rheumatologic manifestations of tuberculosis (TB) and the occurrence of Mycobacterium tuberculosis disease associated with rheumatologic diseases. We established 4 different categories: (1) direct musculoskeletal involvement of M. tuberculosis, including spondylitis, osteomyelitis, septic arthritis, and tenosynovitis; (2) M. tuberculosis as an infectious pathogen in rheumatologic diseases, particularly with the use of newer agents such as tumor necrosis factor-alpha inhibitors; (3) antimycobacterial drug-induced rheumatologic syndromes, including tendinopathy, drug-induced lupus, and others; and (4) reactive immunologic phenomena caused by TB, such as reactive arthritis, erythema nodosum, and others. In addition, Bacille-Calmette-Guérin vaccination used for the prevention of TB or as a chemotherapeutic agent for bladder carcinoma also may be associated with musculoskeletal adverse events. We conclude that M. tuberculosis can directly or indirectly affect the musculoskeletal system.