Fine needle aspiration cytologic diagnosis of erythema nodosum leprosum: a case report

BACKGROUND: Erythema nodosum leprosum (ENL), the type 2 lepra reaction occurring in lepromatous or borderline lepromatous leprosy, presents clinically with acute manifestations that compel the patient to seek medical attention. Recognition and timely management of these patients is critical in order to avoid permanent disability. Fine needle aspiration cytology (FNAC) is a simple, effective tool that aids in correct diagnosis and management of ENL. CASE: A 30-year-old woman presented with history of fever, reddening of the face, and multiple raised, reddish, painful swellings of the bilateral forearms and legs for 7 days. One year previously, she was diagnosed and treated for lepromatous leprosy with type 2 reaction. After a thorough clinical examination a diagnosis of ENL was made. FNA smears from the forearm swellings showed pus-like material with intact and degenerated polymorphonuclear leukocytes and many foamy macrophages with strong granular acid-fast bacillus (AFB) positivity. A cytologic diagnosis of ENL was given, which was confirmed on histopathologic examination of skin biopsy. CONCLUSION: Cytologic features such as a large number of intact and degenerated neutrophils with foamy macrophages and strong granular AFB positivity, in an appropriate clinical background, allows a confident diagnosis of ENL.     

Effect of cyclosporine A in erythema nodosum leprosum

Erythema nodosum leprosum (ENL) is a reactional state of lepromatous leprosy in which the loss of suppressor cell function, decrease in suppressor cell numbers, and increase of interleukin 2 production are observed. We reasoned that cyclosporine A (CsA), by opposing these immune responses, could suppress the ENL reaction and restore patients to the quiescent lepromatous state. We tested this hypothesis in vitro by measuring the effect of CsA on M. leprae-triggered suppressor cells. In 24 of 25 patients with ENL, suppressor cell activity was restored by CsA. The target of CsA appeared to be macrophages. These findings are significant in that they provide the first evidence for the potential efficacy of CsA in the treatment of ENL. Preliminary clinical trials indicate a beneficial therapeutic effect associated with increased T suppressor cells in lesions.     

Ultrastructure of nerve in erythema nodosum leprosum (ENL)

Gross changes of myelinated fibres and Schwann cells at different degenerative stages were present in all five ENL nerve lesions. Besides these changes, infiltrating cells mainly macrophages, deposition of excessive collagen and perineurial vessel damage were also observed.     

Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function

BackgroundThe numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions.MethodsA longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25⁺ cells.Results30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25⁺ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25⁺ cells to CD25⁺ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25⁺ cells either before or after treatment. Depleting CD25⁺ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25⁺ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25⁺ cells.ConclusionThe findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25⁺ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25⁺ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25⁺ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.     

Fatal case of erythema nodosum and histoplasmosis

Summary In the post mortem examination of a patient, erythema nodosum of the upper extremities with fibrinoid arteritis was found in presence of primary pulmonary histoplasmosis with hematogenous dissemination. Sudden death is believed to have been the result of hypersensitivity to acute fungous spread.Prof. Titul. Direct. Inst. Anat. Patol., Universidad de los Andes, Merida Venezuela, Sen. Res. Assoc., Clinical Laboratories, Jewish Hospital, Cincinnati, Ohio (Dr.Jan Schwarz).     

In situ and in vitro characterization of the cellular immune response in erythema nodosum leprosum

We sought to evaluate cell-mediated immune responses in erythema nodosum leprosum (ENL), a reactional state occurring in lepromatous leprosy. Skin biopsies from patients with leprosy were studied with monoclonal antibodies against T lymphocyte antigenic determinants, interleukin 2 (IL 2), and IL 2 receptors (Tac) by using immunoperoxidase staining of frozen sections. Peripheral blood lymphocytes from 18 ENL patients were tested in vitro for lepromin-induced suppression of Con A stimulation. Serial studies of seven lepromatous patients who developed ENL during the course of the study showed increases in both the Leu-3a:Leu-2a ratio and the number of IL 2-positive cells. IL 2-positive cells comprised 0.3% of the cells in all of the ENL lesions studied as compared with the 0.03% found in nonreactional lepromatous lesions (P less than 0.001). Lepromin-induced suppression of the Con A response, present in nonreactional lepromatous patients, significantly decreased in patients developing the ENL reaction, but returned after recovery from ENL. These changes in tissues and peripheral blood suggest that the pathogenesis of ENL is related to cell-mediated immune processes. Despite these immunologic changes, however, ENL patients do not recover antigen-specific skin tests or eliminate Mycobacterium leprae.     

Cytodiagnosis of clear cell hepatocellular carcinoma. A case report.

The cytologic features of clear cell hepatocellular carcinoma are described. This tumor may cause a diagnostic dilemma since it resembles other clear cell tumors originating in the adrenals, kidneys and ovaries. However, clear cell hepatocellular carcinoma possesses some characteristic features that permit a cytologic diagnosis to be made by fine needle aspiration, thus contributing to proper management.     

Serum proteome of leprosy patients undergoing erythema nodosum leprosum reaction: regulation of expression of the isoforms of haptoglobin

Validated proteome profile allows better understanding of disease progression, subtype classification, susceptibility patterns, and disease prognosis. Leprosy is a spectral disease, with clinically, histologically, immunologically, and bacteriologically distinguishable subtypes. In addition, a significant fraction of patients undergo immune mediated reactions even after multidrug therapy (MDT). Erythema nodosum leprosum (ENL) is an immune complex mediated reactional condition in leprosy, characterized by a systemic inflammatory condition afflicting borderline lepromatous (BL) and lepromatous leprosy patients (LL). In this study, we have analyzed serum proteome of leprosy patients undergoing ENL reactions and compared it with that of healthy noncontact controls. Depletion of albumin and immunoglobulin G (IgG) was optimized using Aurum serum protein mini kit (Bio-Rad), and then two-dimensional gel electrophoresis (2-DE) of these serum samples was performed. Differentially expressed proteins were identified by MALDI-TOF and MALDI-TOF MS/MS mass spectrometry. Significant increase in one of the isoforms of alpha2 chain of haptoglobin was observed in ENL condition. In addition, haptoglobin phenotype was determined for healthy controls and leprosy patients. Hp 0-0 phenotype was detected in 21.4% of the ENL patients undergoing treatment, which on follow up examination showed typable phenotype, thus showing a condition of acquired anhaptoglobinemia. Since ENL still remains a threat to leprosy disease management, the above findings may provide new insights in understanding the development and progression of this inflammatory condition.     

Systemic manifestations of erythema nodosum

The systemic manifestations accompanying erythema nodosum can be differentiated from those associated with the precipitating infectious process and from coincident disease processes. Erythema nodosum itself is characterized by (a) skin lesions at pressure sites, (b) malaise, fever and occasionally chills, (c) arthritis (70 per cent) and (d) over-reactivity of tissue. Tissue hypersensitivity is most pronounced at sites of trauma, at sites of specific skin testing, and in the lymphoid system draining infections in the pharynx and lung. Common infections of the respiratory tract most often antedate attacks of erythema nodosum. In New England, a beta-hemolytic streptococcus infection is a common causative factor, and tuberculosis is an unusual causative factor. In endemic areas, coccidioidomycosis is a common cause of erythema nodosum. The most important coincidental disease process is rheumatic heart disease. Rarely is it a sequel of erythema nodosum. Other "collagen diseases" may coexist with erythema nodosum. Erythema nodosum is its own most common complication. Follow-up studies indicate that over half of the patients have a subsequent attack, and a certain number have recurrent episodes for months to years. The management of erythema nodosum is expectant. In each case the cause should be found and treated. Steroid treatment is rarely justified, and should be used only after tuberculosis and other treatable entities have been ruled out.     

Cytodiagnosis of eumycotic mycetoma: a case report

BACKGROUND: Mycetoma is a late-stage clinical manifestation of a subcutaneous infection produced by bacteria (actinomycetoma) or fungi (eumycetoma). Only a few articles have described the morphologic appearance of this uncommon pathology on cytology. The distinction between eumycetoma and actinomycetoma in fine needle aspiration cytology (FNAC) is as accurate as in histopathology, as demonstrated in the present case. CASE: A 30-year-old man presented with a large swelling on his left foot with a discharging sinus. FNAC of the swelling yielded pus-like material. Initial Papanicolaou and Giemsa stains showed the presence of septate, branching fungal hyphae and black granules against the inflammatory background. The presence of fungus was confirmed by PAS stain. The species was identified as Exophiala jeanselmei on fungal culture. CONCLUSION: Mycotic mycetoma can be accurately diagnosed by FNAC, which is a simple, inexpensive and rapid technique when there is a high index of suspicion. Special stains and culture studies are helpful in confirmation of diagnosis and species identification.     

Cytodiagnosis of herpes simplex keratitis by means of an immunoperoxidase technique. A case report

Typical herpes simplex keratitis that developed in a 5-year-old boy was initially diagnosed cytologically in Papanicolaou-stained samples. Subsequently, an immunoperoxidase staining technique was used to identify the specific type of herpes simplex virus (HSV) in the destained cellular samples. The positive staining helped to establish the diagnosis of a type 1 HSV infection, permitting early treatment with acyclovir and subsequent complete recovery from the ocular herpetic infection. Emphasis is placed on the value of the immunoperoxidase technique for the rapid and specific diagnosis of cases of suspected HSV infection.