Sequential erythema nodosum leprosum and reversal reaction with similar lesional cytokine mRNA patterns in a borderline leprosy patient

Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ 21045-900, Brazil.
British Journal of Dermatology (Impact Factor: 4.28). 02/2001; 144(1):175-81. DOI: 10.1046/j.1365-2133.2001.03970.x
Source: PubMed


We compare the clinical and histological data with the immunological status of a borderline leprosy patient who experienced an erythema nodosum leprosum (ENL) reaction followed by a reversal reaction (RR) after 12 weeks of anti-inflammatory treatment (pentoxifylline, PTX, 1200 mg daily). Skin biopsies, serum and blood samples were collected sequentially during the reactional episodes. At the outset of RR, the patient's lymphocytes secreted interferon (IFN) -gamma and there was a positive lymphoproliferative test in response to Mycobacterium leprae, which had been absent during ENL. The lepromin reaction reversed from negative (0 mm) at diagnosis, to positive (3 mm) 3 months after the development of RR. Tumour necrosis factor (TNF) -alpha levels in the serum decreased after 1 week of treatment and increased slightly thereafter. The immunohistochemical data for ENL showed a diffuse dermal and hypodermal infiltrate composed of mononuclear cells and neutrophils, while RR was characterized by an epithelioid granulomatous infiltrate with a marked presence of gammadelta T cells. Reverse transcription-polymerase chain reaction showed a mixed cytokine profile characterized by the expression of TNF-alpha, IFN-gamma, interleukin (IL) -6, IL-10 and IL-12 mRNA in the skin, which persisted throughout the development of ENL and RR lesions. IL-4 mRNA, first detected after 7 days of PTX treatment, was still present during RR. The results suggest the emergence of an initial Th0-like cytokine profile in ENL, typical of a state of immunoactivation, before conditions optimal for the appearance of an antigen-specific cell-mediated immune response and gammadelta T-cell migration are created.

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    • "Meanwhile, the existence of a common underlying control element in LR is a subject that is under discussion. When patients with either LR type were compared with non-reactional leprosy patients, the classical mediators of the cell-mediated immune response were observed at significantly higher levels, both systemically and in the local cutaneous lesions (Modlin et al. 1984, Sreenivasan et al. 1998, Moraes et al. 2001). A pro-inflammatory cytokine of particular interest is the tumour necrosis factor (TNF) as elevations of this cytokine have been observed in the serum and cutaneous lesions of T1R and T2R and in the nerve biopsies of T1R patients (reviewed in Scollard et al. 2006). "
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    ABSTRACT: Type-1 (T1R) and Type-2 (T2R) leprosy reactions (LR), which affect up to 50% of leprosy patients, are aggressive inflammatory episodes of sudden onset and highly variable incidence across populations. LR are often diagnosed concurrently with leprosy, but more frequently occur several months after treatment onset. It is not uncommon for leprosy patients to develop recurring reactional episodes; however, they rarely undergo both types of LR. Today, LR are the main cause of permanent disabilities associated with leprosy and represent a major challenge in the clinical management of leprosy patients. Although progress has been made in understanding the immunopathology of LR, the factors that cause a leprosy patient to suffer from LR are largely unknown. Given the impact that ethnic background has on the risk of developing LR, host genetic factors have long been suspected of contributing to LR. Indeed, polymorphisms in seven genes [Toll-like receptors (TLR)1, TLR2, nucleotide-binding oligomerisation domain containing 2, vitamin D receptor, natural resistance-associated macrophage protein 1, C4B and interleukin-6] have been found to be associated with one or more LR outcomes. The identification of host genetic markers with predictive value for LR would have a major impact on nerve damage control in leprosy. In this review, we present the recent advances achieved through genetic studies of LR.
    Full-text · Article · Dec 2012 · Memórias do Instituto Oswaldo Cruz
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    • "Pathogenesis of type II reaction is thought to be related to the deposition of immune complexes [60]. Increased levels of TNF-α, IL-1β, IFN-γ, and other cytokines in type II reactions are observed [61–63]. In addition, C-reactive protein, amyloid A protein, and α-1 antitrypsin have also been reported to be elevated in ENL patients' sera [64]. "
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    ABSTRACT: Leprosy, also known as Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that has a predilection for the skin and nerves. The disease is clinically characterized by one or more of the three cardinal signs: hypopigmented or erythematous skin patches with definite loss of sensation, thickened peripheral nerves, and acid-fast bacilli detected on skin smears or biopsy material. M. leprae primarily infects Schwann cells in the peripheral nerves leading to nerve damage and the development of disabilities. Despite reduced prevalence of M. leprae infection in the endemic countries following implementation of multidrug therapy (MDT) program by WHO to treat leprosy, new case detection rates are still high-indicating active transmission. The susceptibility to the mycobacteria and the clinical course of the disease are attributed to the host immune response, which heralds the review of immunopathology of this complex disease.
    Full-text · Article · Sep 2012 · Interdisciplinary Perspectives on Infectious Diseases
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    ABSTRACT: Carpotroche brasiliensis is a native Brazilian tree belonging to the Oncobeae tribe of Flacourtiaceae. The oil extracted from its seeds contains as major constituents the same cyclopentenyl fatty acids hydnocarpic (40.5%), chaulmoogric (14.0%) and gorlic (16.1%) acids found in the better known chaulmoogra oil prepared from the seeds of various species of Hydnocarpus (Flacourtiaceae). These acids are known to be related to the pharmacological activities of these plants and to their use as anti-leprotic agents. Although C. brasiliensis oil has been used in the treatment of leprosy, a disease that elicits inflammatory responses, the anti-inflammatory and analgesic activities of the oil and its constituents have never been characterized. We describe the anti-inflammatory and antinociceptive activities of C. brasiliensis seed oil in acute and chronic models of inflammation and in peripheral and central nociception. The mixture of acids from C. brasiliensis administered orally by gavage showed dose-dependent (10-500 mg/kg) anti-inflammatory activity in carrageenan-induced rat paw edema, inhibiting both the edema by 30-40% and the associated hyperalgesia. The acid fraction (200 mg/kg) also showed significant antinociceptive activity in acetic acid-induced constrictions (57% inhibition) and formalin-induced pain (55% inhibition of the second phase) in Swiss mice. No effects were observed in the hot-plate (100 mg/kg; N = 10), rota-road (200 mg/kg; N = 9) or adjuvant-induced arthritis (50 mg/kg daily for 7 days; N = 5) tests, the latter a chronic model of inflammation. The acid fraction of the seeds of C. brasiliensis which contains cyclopentenyl fatty acids is now shown to have significant oral anti-inflammatory and peripheral antinociceptive effects.
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