Image Morphometric Analysis of B Cells and Plasma Cells in Erythema Nodosum Leprosum With Clinicopathological Correlation.

ABSTRACT: Erythema nodosum leprosum (ENL) occurs as an immunological complication of multibacillary leprosy (MBL). The pathogenesis of ENL is long considered to be a T-cell-mediated process. The role of B cells and plasma cells in ENL is not well described in the literature. Therefore, we investigated the B-cell and plasma cell infiltrates in the skin biopsies of biopsy-proven cases of ENL by immunohistochemistry and image morphometry and compared the result with paucibacillary leprosy and MBL. Moreover, we sought a correlation of the B-cell and plasma cell infiltrates with different clinical, hematological, histopathological, and bacteriological parameters as well as the T-cell subsets in the skin biopsies. Our study highlighted a significant reduction in the number of B cells from paucibacillary leprosy to MBL to ENL, although there was no significant variation in the plasma cell infiltrate. The plasma cell infiltrate correlated with absolute neutrophilia in the blood and the presence of eosinophils in the ENL lesions. Both B cells and plasma cells positively correlated with CD4-positive T-helper cells and the CD8-positive cytotoxic T cells. Besides, the B cells also correlated positively with the CD3-positive pan T cells in the biopsy and negatively correlated with the T-regulatory:T-cell ratio. Our results suggested the role of B cells and plasma cells even at the tissue level in the pathobiogenesis of ENL.

Drug reaction with eosinophilia and systemic symptoms: observations from a tertiary care institution.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction which can mimic a viral infection, an autoimmune disease or a neoplastic disease. AIMS: To study the clinical and epidemiological aspects of DRESS and to identify the precipitating drugs. METHODS: All patients admitted to the dermatology ward of our tertiary care hospital from 1 st October 2010 to 30 th September 2013 with probable or definite DRESS as per the RegiSCAR scoring system were included in this prospective study. The clinical manifestations observed in the study population were studied and the common offending drugs were identified. RESULTS: During the 3 year study period, 26 patients fulfilled criteria for probable or definite DRESS. In more than 50% of cases, the culprit drug was phenytoin. Most common symptoms observed were fever, rash and facial edema. Liver was the most common internal organ affected. Most of the patients responded to withdrawal of the drug and administration of steroids for 3-6 weeks. One patient with dapsone-induced DRESS died. CONCLUSIONS: Intense facial erythema and edema and an elevated eosinophil count were not found to be bad prognostic factors. In most instances the flare ups during the course of the disease could be managed with a slower tapering of steroids. More prospective studies on DRESS are required to assess the prognostic factors and to formulate better diagnostic criteria.

Diffuse alopecia areata is associated with intense inflammatory infiltration and CD8+ T cells in hair loss regions and an increase in serum IgE level.

BACKGROUND: Mechanism leading to an abrupt hair loss in diffuse alopecia areata (AA) remains unclear. AIMS: To explore the characteristics of diffuse AA and possible factors involved in its pathogenesis. METHODS: Clinical and laboratory data of 17 diffuse AA patients and 37 patchy AA patients were analyzed retrospectively. Serum IgE level was evaluated in all diffuse and patchy AA patients, as well as 27 healthy subjects without hair loss to serve as normal control. Univariate analysis was performed using Fisher's exact test and Wilcoxon rank-sum test. Associations between inflammatory cell infiltration and laboratory values were analyzed using Spearman rank correlation test. RESULTS: The mean age of patients with diffuse AA was 27 years with a mean disease duration of 1.77 months. All of them presented in spring or summer with an acute onset of diffuse hair loss preceded by higher incidence of scalp pruritus. Although no statistically significant difference on the incidence of atopic disease among three groups has been found, serum IgE level in diffuse AA was higher than that in healthy controls, but was comparable to that in patchy AA group. Histopathology of lesional scalp biopsies showed more intense infiltration comprising of mononuclear cells, eosinophils, CD3 + , and CD8 + T cells around hair bulbs in diffuse AA group than in patchy AA group. Moreover, IgE level in diffuse AA patients positively correlated with intensity of infiltration by mononuclear cells, eosinophils, and CD8 + T cells. CONCLUSIONS: Hypersensitivity may be involved in pathogenesis of diffuse AA. The acute onset of diffuse AA may be related to intense local inflammatory infiltration of hair loss region and an increase in serum IgE level.

No relationship between lung function and high-sensitive C-reactive protein in adolescence.

INTRODUCTION: Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. OBJECTIVE: We explored the temporal relationship between changes in lung function and concentrations of plasma C-reactive protein (CRP) in a population-based cohort study at ages 14 and 20 years using a high-sensitivity CRP assay. METHODS: CRP measurements were performed in a total of 420 subjects at mean age of 13.9 years. Of these, 262 subjects (62%) participated in the follow-up investigation at mean age of 20.1 years. RESULTS: Levels of log-CRP at age 14 were not significantly associated with forced expiratory volume (FEV(1) ) or FEV(1) / forced vital capacity (FVC) ratio at age 20, nor with the change in FEV(1) , FVC or FEV(1) /FVC ratio between 14 and 20 years after controlling for body mass index (BMI), airway hyperresponsiveness (AHR), eosinophil cationic protein (ECP), asthma, smoking, sex, and height at 14 years, and change in height between 14 and 20 years. Sex, BMI, AHR, ECP and change in height between 14 and 20 years were identified as independent factors associated with the change in FEV(1) , FVC and FEV(1) /FVC ratio in adolescence. CONCLUSION: We did not find an association between CRP levels at age 14 and change in lung function by age 20; whereas, sex, change in height, BMI, AHR and ECP were associated with lung function change in adolescence. Our findings indicate that systemic inflammation is of less importance for change in lung function in adolescence. Please cite this paper as: Nybo M, Hansen HS, Siersted HC and Rasmussen F. No relationship between lung function and high-sensitive C-reactive protein in adolescence.

Adult onset, hypopigmented solitary mastocytoma: report of two cases.

Solitary mastocytoma is known to occur predominantly in children below 2 years of age and onset in adulthood is rare. Lesions are hyperpigmented in the majority of cases owing to the stimulation of melanin synthesis by mast cell growth factor. We hereby report two patients with adult onset solitary mastocytoma presenting as hypopigmented plaque. The first case was a 24-year-old man who presented with a plaque on the back of the neck of 5 years duration. The second case was a 30-year-old man who had a well-defined solitary, oval 3 x 2.5 cm plaque on the nape of the neck. Stroking of lesion resulted in a wheal with flare (Darier's sign) in both cases. Systemic examination was within normal limits in both cases. Histopathology revealed a dense toluidine blue-positive infiltrate of mast cells in the upper dermis in both cases.

Crystal-storing histiocytosis due to massive accumulation of charcot-leyden crystals: a unique association producing colonic polyposis in a 78-year-old woman with eosinophilic colitis.

Crystal-storing histiocytosis is a rare diagnosis that to date has only been associated with 2 conditions: intracytoplasmic accumulation of crystallized immunoglobulins in patients with lymphoproliferative disorders or plasma cell dyscrasias, and histiocytic accumulations of phagocytosed clofazimine, a drug used to treat lepromatous leprosy. We describe a 78-year-old woman with a past medical history of dermatologic mastocytosis and peripheral eosinophilia who presented with diarrhea and weight loss, and was found at colonoscopy to have polyposis limited to the right and transverse colon. She eventually underwent subtotal colectomy to remove the segment of polyposis. At gross examination, the colonic mucosa contained numerous polyps ranging from 1 to 7 mm which on histologic evaluation proved to represent mucosal and submucosal collections of histiocytes whose cytoplasm was distended by numerous brightly eosinophilic crystals. An intense eosinophilic infiltrate surrounded the histiocyte collections and also mildly involved the intervening colonic mucosa and superficial submucosa. Electron microscopy confirmed the presence of intracytoplasmic material identical to Charcot-Leyden crystals within histiocytes, representing the breakdown products of degranulated eosinophils. This is the first reported case of crystal-storing histiocytosis produced by massive accumulation of Charcot-Leyden crystals in eosinophilic colitis.

Correlation of the severity of atopic dermatitis with absolute eosinophil counts in peripheral blood and serum IgE levels.

BACKGROUND: Although a number of epidemiological studies, showing incidence and prevalence of atopic dermatitis, were available, scant attention has been paid to the correlation between the parameters of the disease like severity, absolute eosinophil count and IgE level, which has been known to be associated inconsistently. Hence this study was undertaken. METHODS: A total of 102 patients of atopic dermatitis, both children and adults, and 107 age matched controls were studied at the Pediatric Dermatology clinic, Institute of Child Health and department of Dermatology, AMRI-Apollo hospitals, Kolkata. RESULTS: The average age of onset of atopic dermatitis was observed to be 4.55 years. Both the average absolute eosinophil count and IgE levels in patients of atopic dermatitis were significantly higher than that of the controls. Each of these parameters showed significant correlation with severity of the disease and showed a nonhomogeneous distribution reflected by significant association with personal history of bronchial asthma and family history of atopy, when both parents were atopic. CONCLUSIONS: Our study shows that clinical activity of the disease as recorded by the "SCORAD" index can be used as an indicator of the hematological abnormalities as well as to some extent as a prognostic indicator. Family history of atopy correlates with the hematological abnormalities only if both parents are involved and bronchial asthma is the only associated atopic condition which correlates with the parameters of the disease .

Opposite effects of M. leprae or M. bovis BCG delipidation on cellular accumulation into mouse pleural cavity. Distinct accomplishment of mycobacterial lipids in vivo.

OBJECTIVES AND DESIGN: The effect of mycobacterial lipids on the onset of the early acute inflammatory response in BALB/c mice pleurisy was investigated. MATERIALS AND METHODS: Intact Mycobacterium leprae and Mycobacterium bovis BCG (BCG), their lipids, and delipidated mycobacteria were used to evaluate total leukocytes and cell types migrated to the pleural cavity (8 animals/experimental group). RESULTS: BCG Moreau (x10(-6)/cavity), delipidated BCG and its lipids gradually recruited cells leading to arrival, respectively, of neutrophils (7.8+/-1.9, 4.7+/-0.9, 1.8+/-0.25) followed by mononuclear cells (4.8+/-0.8, 3.7+/-0.7, 2.45+/-0.22) and eosinophils (0.39+/-0.08, 0.32+/-0.11, 0.41+/-0.65). BCG delipidation decreased the number of migrated total leukocytes (ANOVA, and Newman-Keuls-Student-test), whereas M. leprae delipidation accumulated neutrophils (0.85+/-0.01) and eosinophils (1.65+/-0.18). CONCLUSIONS: Intact M. leprae and its lipids did not incite any cell recruitment. Apolar external cell wall lipids from M. leprae and BCG induce different cellular responses. They seem to have a crucial importance at the first contact of mycobacteria with the host cell, modulating the influx of neutrophils/macrophages in the early (4/24 h) onset of the inflammatory reaction.

Dapsone induced pulmonary eosinophilia without cutaneous allergic manifestations--an unusual encounter--a case report.

Dapsone is a drug of choice in the treatment of leprosy. In addition it is very useful in the treatment of many other dermatological conditions. The "dapsone-induced hypersensitivity" is not unknown. However, to the best of our knowledge, pulmonary eosinophilia induced by dapsone without any cutaneous allergic manifestation has not been reported in leprosy patients. Pulmonary eosinophilia (Loeffler's syndrome) induced by dapsone without cutaneous manifestation has been reported in a non leprosy patient by Janier et al. We report a case of pulmonary eosinophilia associated with dapsone therapy in a patient with lepromatous leprosy without allergic cutaneous manifestations and our experience in the management of this patient.

Diagnóstico preclínico de la lepra / Preclinical diagnosis of leprosy

El presente estudio trata sobre el diagnóstico preclínico de la lepra utilizando como prueba de laboratorio el Test ELISA. El trabajo incluyé a Ü000 de los 1450 trabajadores de ambos sexos (280 fueron masculinos para el 28 por ciento y 720 femeninos para el 72 por ciento), ya que el resto (450) estaban ausentes del Hospital provincial Celia Sánchez Manduley en el año 1994, por estar considerados como un grupo de riesgo (tasa de prevalencia superior a 1 x 1000 habitantes). Se tomó muestra del suero a las personas incluidas en el estudio y se enviaron al Laboratorio Provincial de Higiene y Epidemiología donde se montaron y procesaron en el SUMA. De las seis muestras que resultaron positivas, 1 correspondió al sexo masculino(16,6 por ciento) y 5 al sexo femenino (83,4 por ciento). A los seis casos se les completó el estudio establecido en el programa, resultando negativos, imponiéndose quimioprofilaxis. Se concluye que el Test ELISA es de gran valor para el diagnóstico preclínico y la prevención de la Lepra.(AU)

Nongranulomatous involvement of the bone marrow in lepromatous leprosy.

Bone marrow involvement in lepromatous leprosy has been characterized histologically by a proliferation of foamy histiocytes containing lepra bacilli, the so-called Virchow cells. The authors have studied three patients with biopsy-proven lepromatous leprosy in whom Fite stain, performed on histologic sections of bone marrow aspirates, demonstrated numerous bacilli lying free in the interstitium in the absence of Virchow cells or focal collections of foamy macrophages. Two of the patients had a recent diagnosis of lepromatous leprosy by skin biopsy; the third patient had a 33-year history of lepromatous leprosy that had been treated. Bone marrow aspirates were performed in all three patients for evaluation of anemia. The findings indicate that the bone marrow may act as a reservoir for viable organisms in the absence of a host response in treated and untreated patients with lepromatous leprosy. The persistence of viable organisms in the bone marrow in patients with lepromatous leprosy may account for the high rate of relapse and/or recrudescence of the disease following cessation of specific therapy. Bone marrow examination with the Fite modification of the acid-fast stain is therefore indicated in such patients to evaluate bone marrow involvement and the efficacy of treatment.

Does dexamethasone suppress the Mazzotti reaction in patients with onchocerciasis?

The Mazzotti reaction is a frequent complication in patients with onchocerciasis being treated with diethylcarbamazine (DEC); and more severe manifestations of this reaction may be unacceptable in many patients. It has recently been demonstrated that prednisone modifies the severity of this reaction and reduces the microfilaricidal activity of DEC. A clinical trial was performed at the National Leprosy Training Center in Wau, Sudan, to evaluate the clinical and histologic effect of the use of corticosteroids in patients receiving DEC. Administration of a low dose of dexamethasone (3 mg/day), begun after onset of the Mazzotti reaction, modifies the progression of the Mazzotti reaction without interfering with the microfilaricidal efficacy of DEC. Pretreatment with low-dose dexamethasone--prior to beginning DEC therapy--prevents the development of the Mazzotti reaction and greatly reduces the microfilaricidal activity. Administration of diphenhydramine, after onset of the Mazzotti reaction, has no effect on the course and intensity of the Mazzotti reaction nor on microfilaricidal activity. We recommend that low-dose corticosteroids be administered in conjunction with DEC--after onset of the Mazzotti reaction--and that they be tapered rapidly.

Toxic effect of the peroxidase-hydrogen peroxide-halide antimicrobial system on Mycobacterium leprae.

Mycobacterium leprae are killed by myeloperoxidase (or eosinophil peroxidase), H2O2, and a halide, thus suggesting a mechanism for their destruction by peroxidase-containing phagocytes.