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Journal articles on the topic 'Erythema nodosum, Reversal reaction'

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Published: 4 June 2021

Last updated: 1 February 2022

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1

Pulido-Pérez, A., M. D. Mendoza-Cembranos, J. A. Avilés-Izquierdo, and R. Suárez-Fernández. "Erythema Nodosum Leprosum and Reversal Reaction in 2 Cases of Imported Leprosy." Actas Dermo-Sifiliográficas (English Edition) 104, no. 10 (December 2013): 915–19. http://dx.doi.org/10.1016/j.adengl.2012.09.024.

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2

Chopra, Ajay, and Debdeep Mitra. "1345. Randomized Control Trial to Evaluate the Clinical and Cytokine Response Profile to Oral Thalidomide in Leprosy Patients with Erythema Nodosum Leprosum." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S487. http://dx.doi.org/10.1093/ofid/ofz360.1209.

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Abstract Background Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Erythema Nodosum Leprosum is an acute inflammatory Type III hypersensitivity response during the chronic course of the disease process. This immune response manifests clinically as painful red nodules and systemic symptoms similar to sepsis with neutrophilic leukocytosis. Capsule Thalidomide is the drug of choice for treating this condition. Methods A randomized control study to study the immunological markers involved in the pathogenesis of erythema nododsum leprosum and its successful suppression by Thalidomide should provide newer insight into the pathogenesis of this disease process, provide better diagnostic and therapeutic options and better markers to predict prognosis. Based on the previous studies our aim was to find a correlation with tumor necrosis factor-a, interferon-gamma, and Cd-64 expression on activated circulating neutrophils during Type II lepra reaction and the successful response to capsule Thalidomide. Venous blood samples were collected from all the samples and after 7 days post thalidomide therapy, only in the treated population. All the patients with type II lepra reaction responded to Capsule Thalidomide clinically and all the skin lesions resolved in 7–14 days. Blood samples and skin biopsy was subjected to histopathology, immunofluorescence assay, immunohistochemical staining, quantitative RT–PCR (reverse transcriptase-polymerase chain reaction) and flow cytometry. Results Study found out that Interferon Γand Tumor necrosis factor-Α are sensitive markers in diagnosing erythema nodosum leprosum and Cd-64 expression on activated circulating neutrophils is both a specific and sensitive marker. Cd-64 expression also had a positive correlation with Thalidomide treatment and clinical response. Conclusion Cd-64 expression on circulating neutrophils is a potential early biophysical marker for diagnosing erythema nodosum leprosum and can be used as a tool to assess thalidomide response. InterferonΓ and Tumor necrosis factorΑ are sensitive markers to screen for lepra reactions and this study showed no significant correlation with Thalidomide therapy. Disclosures All authors: No reported disclosures.

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Chopra, Ajay, Debdeep Mitra, and Barnali Mitra. "812. Case–Control Trial to Evaluate the Cytokine Response to the Use of Capsule Thalidomide in Erythema Nodosum Leprosum in Leprosy Patients." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S290—S291. http://dx.doi.org/10.1093/ofid/ofy210.819.

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Abstract Background Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Type II lepra reaction or Erythema Nodosum Leposum is a Type III hypersentivity immune response during the chronic course of the illness. This immune response presents as systemic symptoms and neutrophilic leukocytosis, similar to sepsis. Capsule Thalidomide is considered the drug of choice, when it comes to the treatment of this acute immunological emergency. A rational study into the immunological markers involved in the pathogenesis of erythema nododsum leprosum and its successful suppression by Thalidomide should be helpful in early diagnosis and prompt successful therapy. On the basis of previous studies, our aim was to find a correlation with interferon-γ, tumour necrosis factor-α, and Cd-64 expression on activated circulating neutrophils during Type II lepra reaction and successful response to capsule Thalidomide. Methods This case-controlled study included one group of patients diagnosed to have leprosy and the other group was healthy controlled individuals with matched age, sex, and area of residence. All the patients with type II lepra reaction responded to Capsule Thalidomide clinically, and all the skin lesions resolved in 7–14 days. Blood samples and skin biopsy were subjected to histopathology, immunoflourescence assay, immunohistochemical staining, quantitative RT-PCR (reverse transcriptase-polymerase chain reaction), and flow cytometry. Results Interferon-γ and TNF-α are sensitive markers in diagnosing erythema nodosum leprosum and Cd-64 expression on activated circulating neutrophils is both a specific and sensitive marker in Type II lepra reaction. Cd-64 expression also had a positive correlation with Thalidomide treatment and clinical response. High polymorphonuclear Cd-64 expression was correlated with severity of ENL. Conclusion Cd-64 expression on circulating neutrophils is a potential early biophysical marker for diagnosing erythema nodosum leprosum and can be used as a tool to assess thalidomide response. It is however not a good index to diagnose leprosy infection as it was specific for Type II lepra reaction. Interferon-γ and TNF-α are sensitive markers to screen for lepra reactions and this study showed no significant correlation with Thalidomide therapy. Disclosures All authors: No reported disclosures.

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4

Cooper, C. L., C. Mueller, T. A. Sinchaisri, C. Pirmez, J. Chan, G. Kaplan, S. M. Young, I. L. Weissman, B. R. Bloom, and T. H. Rea. "Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization." Journal of Experimental Medicine 169, no. 5 (May 1, 1989): 1565–81. http://dx.doi.org/10.1084/jem.169.5.1565.

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Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.

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5

Tsaqilah, Laila, Pati Achdiat, and Hendra Gunawan. "Reversal reaction with nodules that initially diagnosed as erythema nodosum leprosum in borderline lepromatous leprosy." Journal of General-Procedural Dermatology and Venereology Indonesia 5, no. 1 (December 31, 2020): 68–73. http://dx.doi.org/10.19100/jdvi.v5i1.159.

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6

Cossermelli-Messina, Waldenise, and Wilson Cossermelli. "Possible mechanisms of chronic leprosy-related arthritis." Sao Paulo Medical Journal 115, no. 2 (April 1997): 1406–9. http://dx.doi.org/10.1590/s1516-31801997000200007.

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Microbial agents induce arthritis through mechanisms such as direct infiltration of tissue and by inducing autoimmune phenomena. The mechanisms involved in this last type of arthritis have been investigated. In experimental models of adjuvant and reactive arthritis, the involvement of T cells and in some cases mycobacteria in the development of arthritis have been confirmed. Cross-reactivity between the 65 kD mycobacterial protein and cartilage proteoglycans has been postulated as a possible mechanism. In this study, chronic peripheral arthritis was observed in patients with Hansen's disease, in patients with resolved Hansen's and in those with paucibacillary forms. This arthritis was not related to reactional states (erythema nodosum Ieprosum and reversal reaction), in contrast to several reports in the literature. The mechanisms by which microbes could induce chronic arthritis are discussed herein.

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7

Amorim, Francianne M., Maurício L. Nobre, Larissa S. Nascimento, Alesson M. Miranda, Glória R. G. Monteiro, Francisco P. Freire-Neto, Maria do Carmo Palmeira Queiroz, et al. "Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum." PLOS Neglected Tropical Diseases 13, no. 1 (January 28, 2019): e0007089. http://dx.doi.org/10.1371/journal.pntd.0007089.

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8

Moraes, M. O., E. P. Sampaio, J. A. C. Nery, B. C. C. Saraiva, F. B. F. Alvarenga, and E. N. Sarno. "Sequential erythema nodosum leprosum and reversal reaction with similar lesional cytokine mRNA patterns in a borderline leprosy patient." British Journal of Dermatology 144, no. 1 (January 2001): 175–81. http://dx.doi.org/10.1046/j.1365-2133.2001.03970.x.

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9

NERY, José A. C., Leila M. M. VIEIRA, Haroldo J. de MATOS, Maria E. N. GALLO, and Euzenir N. SARNO. "REACTIONAL STATES IN MULTIBACILLARY HANSEN DISEASE PATIENTS DURING MULTIDRUG THERAPY." Revista do Instituto de Medicina Tropical de São Paulo 40, no. 6 (November 1998): 363–70. http://dx.doi.org/10.1590/s0036-46651998000600005.

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It is well known that reactions are commonplace occurrences during the course of leprosy disease. Stigmatization may even be attributable to reactions which are also responsible for the worsening of neural lesions. A cohort of 162 newly-diagnosed baciloscopically positive patients from the Leprosy Care Outpatient Clinic of the Oswaldo Cruz Foundation (FIOCRUZ) was selected for this study. While 46% of the multibacillary (MB) patients submitted to the 24 fixed-dose multidrug therapy (MDT) regimen suffered reactions during treatment, it was found that all MBs were susceptible and that constant attention and care were required at all times. Fourteen per cent were classified as BB, 52% as BL, and 33% as LL. None of the variables under study, such as, sex, age, clinical form, length of illness, length of dermatological lesions, baciloscopic index (BI), or degree of disability proved to be associate with reaction among the patients studied. Reversal Reaction (RR) occurred in 45%, and Erythema Nodosum Leprosum (ENL) occurred in 55%. Among BB patients who developed reactions (15 patients), 93% presented RR; while among the LL patients who developed reactions (34 patients), 91% presented ENL. Likewise, ENL was very frequent among those with disseminate lesions, while RR was most often observed in patients with segmentary lesions. RR was also most likely to occur during the initial months of treatment. It was demonstrated that the recurrence rate of ENL was significantly higher than that of RR. Neither grade of disability nor BI was shown to be associated with RR and ENL reaction. However, the RR rate was significantly higher among patients showing BI < 3, while ENL predominated among those patients with BI > 3.

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Gupta, Nishma, Nallakandy P. Shankernarayan, and Kuppamuthu Dharmalingam. "α 1-Acid glycoprotein as a putative biomarkerfor monitoring the development of the type II reactional stage of leprosy." Journal of Medical Microbiology 59, no. 4 (April 1, 2010): 400–407. http://dx.doi.org/10.1099/jmm.0.016394-0.

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Leprosy, a spectral disease manifested on the basis of host immune responses,is complicated by its reactional stages, namely type I reversal reaction (RR)and type II erythema nodosum leprosum (ENL). These reactional stagesare characterized by uncontrolled and aberrant immune responses. Biomarkersfor reactional stages would aid in early diagnosis, efficient treatment, preventionof neurological complications and prediction of predisposition to reactionalstages. In this study, comparative analysis of the serum proteome of leprosypatients by two-dimensional electrophoresis (2DE) followed by massspectrometry showed differential expression of acute-phase protein α 1-acid glycoprotein (AGP; also known as orosomucoid).AGP levels in untreated ENL cases were significantly higher than in lepromatousleprosy (LL; a non-reactional disease stage) (P=0.0126),RR (P=0.0176) and healthy controls (P=0.0030).These data were confirmed using ELISA. The levels of AGP decreased to normallevels after treatment with multidrug therapy and thalidomide (P=0.0167). In a follow-up study, AGP levels, which were highin the untreated ENL stage, decreased significantly at 5 days (P=0.0084) and 21 days (P=0.0027)post-treatment. A stage-dependent increase in AGP in an LL patient who progressedinto the ENL stage was also shown. Glycosylation analysis by 2DE showed differentialexpression of acidic glycoforms of AGP in untreated ENL cases. Changes inAGP concentration and differential expression of isoforms correlated withthe inflammatory condition in ENL and also with the treatment regimen. Thus,initial validation of AGP as an ENL-specific biomarker and treatment indicatorwas shown in this study.

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Saini, Chaman, H. K. Prasad, Rajni Rani, A. Murtaza, Namita Misra, N. P. Shanker Narayan, and Indira Nath. "Lsr2 of Mycobacterium leprae and Its Synthetic Peptides Elicit Restitution of T Cell Responses in Erythema Nodosum Leprosum and Reversal Reactions in Patients with Lepromatous Leprosy." Clinical and Vaccine Immunology 20, no. 5 (February 27, 2013): 673–82. http://dx.doi.org/10.1128/cvi.00762-12.

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ABSTRACTThe Lsr2 protein ofMycobacterium lepraeand its synthetic peptides have been shown to elicit lymphoproliferation and gamma interferon (IFN-γ) release by peripheral blood mononuclear cells (PBMCs) of patients with lepromatous leprosy (M. Chaduvula, A. Murtaza, N. Misra, N. P. Narayan, V. Ramesh, H. K. Prasad, R. Rani, R. K. Chinnadurai, I. Nath, Infect. Immun. 80:742–752, 2012). PBMCs from 16 patients with lepromatous leprosy who were undergoing erythema nodosum leprosum (ENL) (type 2) and 5 patients with reversal reactions (RR) (type 1) were stimulated withM. leprae, recombinant Lsr2, and six end-to-end synthetic peptides (A through F) spanning the Lsr2 sequence. During the reaction all patients with ENL showed lymphoproliferation (stimulation index, >2) in response to peptides A and F, with other peptides eliciting responses in 75 to 88% of the subjects. In PBMC cultures, both lymphoproliferation and IFN-γ release for peptide E were significantly higher than for peptides B and C and recombinant Lsr2 (P< 0.05, Wilcoxon signed-rank test). Five patients with RR also showed enhanced lymphoproliferative responses and IFN-γ release in response to Lsr2,M. leprae, and peptide E. Six months postreaction, 14 patients with ENL continued to exhibit responses to Lsr2 and its peptides, with the highest responses being elicited by peptide E. However, 5 subjects showed no lymphoproliferation and had reduced IFN-γ release in response to Lsr2 peptides (P< 0.001, Kruskal-Wallis test) but responded to recombinant Lsr2. Six patients with ENL had HLA-A*68.01, which the STFPEITHI program showed to have high peptide-binding scores of 20 to 21 for peptides E, B, and C. Eleven patients had HLA-DRB1*1501 and HLA-DRB1*1502, which had high binding scores for peptides C and E. Thus, Lsr2 and its peptides are recognized in leprosy reactions during and well after the subsidence of clinical signs.

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Motta, Ana Carolina F., Renata Bazan Furini, João Carlos Lopes Simão, Maria Aparecida Nunes Ferreira, Marilena C. Komesu, and Norma T. Foss. "The recurrence of leprosy reactional episodes could be associated with oral chronic infections and expression of serum IL-1, TNF-α, IL-6, IFN-γ and IL-10." Brazilian Dental Journal 21, no. 2 (2010): 158–64. http://dx.doi.org/10.1590/s0103-64402010000200012.

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The aim of this study was to determine whether the presence of leprosy reactional episodes could be associated with chronic oral infection. Thirty-eight leprosy patients were selected and divided into 2 groups: group I - 19 leprosy patients with oral infections, and group II - 19 leprosy patients without oral infections. Ten patients without leprosy, but presenting oral infections, were assigned to the control group. Leprosy patients were classified according to Ridley and Jopling classification and reactional episodes of the erythema nodosum type or reversal reaction were identified by clinical and histopathological features associated with serum IL-1, TNF-α, IL-6, IFN-γ and IL-10 levels. These analyses were performed immediately before and 7 days after the oral infection elimination. Patients from group I presenting oral infections reported clinical improvement of the symptoms of reactional episodes after dental treatment. Serum IL-1, TNF-α, IL-6, IFN-γ and IL-10 levels did not differ significantly before and after dental treatment as determined by the Wilcoxon test (p>0.05). Comparison of the 2 groups showed statistically significant differences in IL-1 and IL-6 at baseline and in IL-1, IL-6 and IL-10 on the occasion of both collections 7 days after therapy. Serum IL-6 and IL-10 levels in group I differed significantly at baseline compared to control (Mann-Whitney test; p<0.05). These results suggest that oral infection could be involved as a maintenance factor in the pathogenesis of leprosy reactional episodes.

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Antunes, Sérgio Luiz Gomes, Yong Liang, José Augusto da Costa Neri, Mary Haak-Frendscho, and Olle Johansson. "The expression of NGFr and PGP 9.5 in leprosy reactional cutaneous lesions: an assessment of the nerve fiber status using immunostaining." Arquivos de Neuro-Psiquiatria 61, no. 2B (June 2003): 346–52. http://dx.doi.org/10.1590/s0004-282x2003000300005.

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The effects of reactional episodes on the cutaneous nerve fibers of leprosy patients was assessed in six patients (three with reversal reactions and three with erythema nodosum leprosum). Cryosections of cutaneous biopsy of reactional lesions taken during the episode and of another sample during the remission period were immunostained with anti-NGFr and anti-PGP 9.5 (indirect immunofluorescence). We found no significant statistical difference in the number of NGFr- and PGP 9.5-positive fibers between the reactional and post-reactional groups. A significant difference was detected between the number of NGFr and PGP 9.5-stained fibers inside of the reactional group of biopsy cryosections but this difference was ascribed to the distinct aspects of the nerve fibers displayed whether stained with anti-NGFr or with anti-PGP 9.5; NGFr-positive branches looked larger and so interpreted as containing more fibers. In addition, a substantial number NGFr-positive fibers were PGP 9.5-negative. No differences in the number of stained fibers among the distinct cutaneous regions examined (epidermis + upper dermis, mid and deep dermis) was detected. In conclusion, the number of PGP- and NGFr-positive fibers were not significantly different in the reactional and post-reactional biopsies in the present study. NGFr-staining of the nerve fibers is different from their PGP-imunoreactivity and the evaluation of the nerve fiber status on an innervated target organ should be carried out choosing markers for both components of nerve fibers (Schwann cells and axons).

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14

Teles, Rosane M. B., Rose B. Teles, Thais P. Amadeu, Danielle F. Moura, Leila Mendonça-Lima, Helen Ferreira, Ítalo M. C. F. Santos, José A. C. Nery, Euzenir N. Sarno, and Elizabeth P. Sampaio. "High Matrix Metalloproteinase Production Correlates with Immune Activation and Leukocyte Migration in Leprosy Reactional Lesions." Infection and Immunity 78, no. 3 (December 14, 2009): 1012–21. http://dx.doi.org/10.1128/iai.00896-09.

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ABSTRACT Gelatinases A and B (matrix metalloproteinase 2 [MMP-2] and MMP-9, respectively) can induce basal membrane breakdown and leukocyte migration, but their role in leprosy skin inflammation remains unclear. In this study, we analyzed clinical specimens from leprosy patients taken from stable, untreated skin lesions and during reactional episodes (reversal reaction [RR] and erythema nodosum leprosum [ENL]). The participation of MMPs in disease was suggested by (i) increased MMP mRNA expression levels in skin biopsy specimens correlating with the expression of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), (ii) the detection of the MMP protein and enzymatic activity within the inflammatory infiltrate, (iii) increased MMP levels in patient sera, and (iv) the in vitro induction of MMP-9 by Mycobacterium leprae and/or TNF-α. It was observed that IFN-γ, TNF-α, MMP-2, and MMP-9 mRNA levels were higher in tuberculoid than lepromatous lesions. In contrast, interleukin-10 and tissue inhibitor of MMP (TIMP-1) message were not differentially modulated. These data correlated with the detection of the MMP protein evidenced by immunohistochemistry and confocal microscopy. When RR and ENL lesions were analyzed, an increase in TNF-α, MMP-2, and MMP-9, but not TIMP-1, mRNA levels was observed together with stronger MMP activity (zymography/in situ zymography). Moreover, following in vitro stimulation of peripheral blood cells, M. leprae induced the expression of MMP-9 (mRNA and protein) in cultured cells. Overall, the present data demonstrate an enhanced MMP/TIMP-1 ratio in the inflammatory states of leprosy and point to potential mechanisms for tissue damage. These results pave the way toward the application of new therapeutic interventions for leprosy reactions.

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Morato-Conceicao, Yvelise T., Eduardo R. Alves-Junior, Talita A. Arruda, Jose C. Lopes, and Cor J. F. Fontes. "Serum uric acid levels during leprosy reaction episodes." PeerJ 4 (March 14, 2016): e1799. http://dx.doi.org/10.7717/peerj.1799.

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Background.Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions.Methods.The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively).Results.A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment.Discussion.The decreased serum UA levels in patients with type 2 leprosy reactions might be due to the consumption of UA to neutralize the enhanced production of oxygen- and nitrogen-reactive species that occurs during type 2 reactions. The maintenance of the reduced levels in the follow-up assessments may indicate persistence of oxidative stress in the initial post-treatment stages, despite improved clinical conditions. The results of this study suggest that serum UA may play an antioxidative role during type 2 leprosy reactions.

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Kaur, Navdeep. "Histopathological features of relapse cases in leprosy." International Journal of Research in Medical Sciences 8, no. 11 (October 28, 2020): 4099. http://dx.doi.org/10.18203/2320-6012.ijrms20204466.

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Leprosy is unique in terms of the nature of the causative organism (Mycobacterium leprae), the chronicity of the disease, its prolonged treatment and the definitions of “cure” and “relapse.” The principal mode of assessing the efficacy of therapeutic regimens in leprosy is the “relapse rate.” There are wide variations in estimates of relapse rates after the World Health Organization (WHO) multidrug therapy in different regions. The important predisposing factors for relapse include the presence of “persister” bacilli, monotherapy, inadequate/irregular therapy, presence of multiple skin lesions/thickened nerves and lepromin negativity. The conventional methods of confirming activity or relapse in an infectious disease (demonstration and/or culture of the etiologic agent) have limited utility in leprosy because of the difficulty in demonstrating bacilli in paucibacillary (PB) cases and absence of a method of in vitro cultivation of M. leprae. Bacteriological parameters are useful in multibacillary (MB) leprosy, whereas in PB leprosy, the criteria for relapse depend primarily on clinical features. Although there are no widely available serologic tests for leprosy other than in a research setting, various immunological tests may be useful for monitoring patients on chemotherapy as well as for confirming suspected cases of relapse. The main differential diagnoses for relapse are reversal reactions, erythema nodosum leprosum and reactivation/resistance/reinfection. The most reliable criteria for making an accurate diagnosis of relapse include clinical, bacteriological and therapeutic criteria. Additional ones that may be used, depending on the setting, are histopathological and serologic criteria.

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Semenova, Viktoria G., Ludmila L. Makarova, and Arfenya E. Karamova. "Erythema nodosum as Leprosy reaction." Vestnik dermatologii i venerologii 96, no. 3 (September 29, 2020): 68–74. http://dx.doi.org/10.25208/vdv1159.

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Purpose.To present a clinical case of leprosy exacerbation on the background of ongoing therapy. Materials and methods.A 52-year-old patient with a diagnosis of "lepromatous (cutaneous) leprosy, leprosy LL" (multi-bacterial leprosy, lepromatous form, active stage), has an exacerbation in the form of nodular erythema at 3.5 years after the start of treatment. Due to the exacerbation of the leprosy process, dexamethasone therapy was performed intravenously in a dose of 4 mg/ml 3.0 ml + 0.9% NaCl 200.0 ml daily No. 10. Results. An exacerbation was diagnosed leprosy nodular erythema. The prescription of adequate therapy led to a complete regression of clinical manifestations. Conclusion.The described case is presented in connection with the rarity of this dermatosis.

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Sethuraman, Gomathy, Divakaran Jeevan, Chakravarthy Rangachary Srinivas, and Gopal Ramu. "Bullous erythema nodosum leprosum (bullous type 2 reaction)." International Journal of Dermatology 41, no. 6 (June 2002): 362–64. http://dx.doi.org/10.1111/j.1365-4632.2002.1428_2.x.

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19

González-Olivares, M., R. Khedaoui, C. Martínez-Morán, and J. Borbujo. "Azathioprine-Induced Hypersensitivity Reaction Presenting as Erythema Nodosum." Actas Dermo-Sifiliográficas (English Edition) 108, no. 6 (July 2017): 591–93. http://dx.doi.org/10.1016/j.adengl.2017.05.003.

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20

Babamahmoodi, Farhanag, Abdolreza Babamahmoodi, Hamidreza Barani, and Leila Delavarian. "Simultaneous Occurrence of Erythema Nodosum in Monozygotic Twin Sisters." Case Reports in Medicine 2012 (2012): 1–4. http://dx.doi.org/10.1155/2012/109427.

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Erythema nodosum (EN) is the most frequent clinicopathologic variant of panniculitis with painful red or violaceous nodules on the anterior surfaces of the legs. The condition is a cutaneous reaction that might be associated with a wide variety of disorders or might be caused by medications that produce painful nodules on the shins, and less commonly on the thighs and forearms. In this paper, we describe, for the first time in the world, erythema nodosum as the simultaneous presenting complaint of monozygotic twin sisters after streptococcal pharyngitis. This paper might support the effect of heredity in the occurrence of erythema nodosum.

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Laroche, Alexandre, Evelyn Alarcon Chinchilla, Emilie Bourgeault, and Marc-André Doré. "Erythema Nodosum as the Initial Presentation of Nivolumab-Induced Sarcoidosis-Like Reaction." Journal of Cutaneous Medicine and Surgery 22, no. 6 (May 17, 2018): 627–29. http://dx.doi.org/10.1177/1203475418776934.

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Background: We report a case of nivolumab-related sarcoidosis-like syndrome that initially presented with erythema nodosum. Sarcoidosis development has been described in single and combination immunotherapy. Case Presentation: A 68-year-old white woman with metastatic ocular amelanotic choroid melanoma was treated with nivolumab. The patient developed histologically confirmed erythema nodosum lesions and pulmonary granuloma sarcoidosis. Nivolumab was discontinued and the patient started ipilimumab therapy. Conclusion: Sarcoidosis-like syndrome with lymphadenopathy is a rare adverse event that is important to recognize since it can be mistaken for metastatic disease progression. Tissue biopsy of new lesions during immunotherapy is an important step in patient evaluation.

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Papaiordanou, Francine, Bruno Rebelo Lages da Silveira, and Luna Azulay Abulafia. "Hypersensitivity reaction to Sporothrix schenckii: erythema nodosum associated with sporotrichosis." Revista da Sociedade Brasileira de Medicina Tropical 48, no. 4 (August 2015): 504. http://dx.doi.org/10.1590/0037-8682-0111-2015.

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Mahajan, Rahul, Sunil Dogra, Inderjeet Kaur, Savita Yadav, Uma Nahar Saikia, and Anil Budania. "Type II reaction without erythema nodosum leprosum masquerading as lymphoma." Leprosy Review 83, no. 4 (December 1, 2012): 378–83. http://dx.doi.org/10.47276/lr.83.4.378.

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Uce Özkol, Hatice, Ömer Çalka, and İrfan Bayram. "Diffused Erythema Nodosum Leprosum Reaction with Necrotic Ulcers: Case Report." Turkish Journal of Dermatology / Türk Dermatoloji Dergisi 12, no. 2 (June 8, 2018): 113–15. http://dx.doi.org/10.4274/tdd.2325.

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Ray, Rudranarayan, Rajib Kumar Mondal, and Swapan Pathak. "Diagnosis of Erythema Nodosum Leprosum (Type 2 Reaction) by Cytology." Acta Cytologica 58, no. 1 (2014): 29–32. http://dx.doi.org/10.1159/000356010.

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Heng, Yee-Kiat, Yuun-Tirng Lynn Chiam, Yoke-Chin Giam, and Wei-Sheng Chong. "Lepromatous leprosy in erythema nodosum leprosum reaction mimicking Sweet’s syndrome." International Journal of Dermatology 50, no. 9 (August 19, 2011): 1124–25. http://dx.doi.org/10.1111/j.1365-4632.2010.04686.x.

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Hassan, Ali, Amna Alsaihati, Malak Al Shammari, Mohammed Sharroufna, Haitham Alaithan, and Salman Aljubran. "Erythema Nodosum: A Manifestation of Salmonella Infection." Case Reports in Gastroenterology 13, no. 3 (October 30, 2019): 456–61. http://dx.doi.org/10.1159/000503894.

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Erythema nodosum is a delayed-type hypersensitivity reaction with an unknown trigger in the majority of cases. It is characterized by the development of erythematous tender nodules on the shins. Septal panniculitis without vasculitis is a characteristic histopathological finding. We report the case of a 26-year-old woman who presented with a four-day history of an erythematous swollen left lower limb. She was treated with intravenous clindamycin for suspected cellulitis. However, her symptoms persisted. Punch biopsy revealed findings consistent with erythema nodosum. Two days later, she developed colicky abdominal pain associated with non-bloody diarrhea. Stool culture yielded Salmonella enterica serotype enteritidis. Two days after discharge, she presented again with a right breast abscess for which she underwent incision and drainage along with antibiotic therapy. After discharge, she was symptom-free with complete resolution of the cutaneous lesions. The presented case is unique as it had multiple clinical manifestations of Salmonella infection including erythema nodosum, diarrhea, and presumably a breast abscess. It should be kept in mind that gastrointestinal symptoms are not necessarily the initial presentations of Salmonella infection.

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Lee, Mi-Woo, Jee-Ho Choi, Kyung-Jeh Sung, Kee-Chan Moon, and Jai-Kyoung Koh. "Interstitial and Granulomatous Drug Reaction Presenting as Erythema Nodosum-like Lesions." Acta Dermato-Venereologica 82, no. 6 (November 1, 2002): 473–74. http://dx.doi.org/10.1080/000155502762064692.

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Richards, W. Edward, Mark B. Reedy, Kevin P. Huddleston, and Jeffrey W. Jundt. "Erythema Nodosum Associated With Streptococcal Infection in Pregnancy." Infectious Diseases in Obstetrics and Gynecology 3, no. 4 (1995): 166–68. http://dx.doi.org/10.1155/s1064744995000536.

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Background: Erythema nodosum (EN) is a condition characterized by the presence of painful erythematous nodules on the pretibial aspects of the lower extremities. EN is thought to be a local inflammatory, immune-mediated reaction to a number of systemic antigenic stimuli. This condition is noted most often in women between menarche and menopause and is associated with certain drugs, infections, and pregnancy. However, no reports in the literature describe EN as a result of streptococcal infection during pregnancy.Case: A 21-year-old, white woman, G3P0020, presented at 13 weeks gestation with a 2-week history of erythematous, tender lesions on the pretibial aspects of both legs consistent with EN. The patient reported having had a “flu-like” illness at the same time the lesions developed. The “flu” symptoms resolved within 10 days without medical intervention, but the lesions on her legs persisted. An initial antistreptolysin-O (ASO) titer was elevated at 960 Todd units (normal values: preschool and adults <85; school-age and young adults <170). Six days later, she presented to the emergency department with complaints consistent with a urinary-tract infection. She was empirically treated with a 10-day course of amoxicillin, 500 mg t.i.d. Although the patient was treated with amoxicillin for a presumed urinary-tract infection (which was culture-negative), the lesions resolved after her completion of the antibiotics. Twelve weeks later, a repeat ASO was within normal limits. The EN lesions did not recur.Conclusion: Although many etiologic factors are identified as causes of EN, the condition is usually self-limiting, requiring only minimal supportive measures until it resolves. A careful history should be obtained and a physical examination performed to exclude other causes. If a recent streptococcal infection is identified or presumed, a 10- to 14-day course of antibiotics is warranted.

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Vargas-Hitos, JoseAntonio, JoseMario Sabio, Jesús Tercedor, Nuria Navarrete-Navarrete, and Juan Jiménez-Alonso. "Erythema nodosum as azathioprine hypersensitivity reaction in a patient with bullous pemphigoid." Indian Journal of Dermatology 58, no. 5 (2013): 406. http://dx.doi.org/10.4103/0019-5154.117332.

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Angoori, Gnaneshwar R., Farheen S. Syeda, Amit Kolli, Aparna Karanam, Uday R. Deshmukh, Ruhi Haqqani, Kranthi Jagadevapuram, and Sandhya R. Thoneparti. "Annular erythema nodosum leprosum reaction in a young male: a rare presentation." International Journal of Dermatology 57, no. 4 (February 2, 2018): 500–501. http://dx.doi.org/10.1111/ijd.13927.

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Seban, Romain-David, Camille Vermersch, Laurence Champion, Benjamin Bonsang, Anissa Roger, and Jerome Ghidaglia. "Immune-Related Erythema Nodosum Mimicking in Transit Melanoma Metastasis on [18F]-FDG PET/CT." Diagnostics 11, no. 5 (April 22, 2021): 747. http://dx.doi.org/10.3390/diagnostics11050747.

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Early detection of immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) is crucial, particularly when these are likely to mimic tumor progression, as well as sarcoid-like reactions. Here, we report the case of a 68-year woman, with a history of four primary cutaneous melanomas (thickest lesion with BRAF mutation removed from the left axilla 2 years before), who was diagnosed with BRAF V600E-mutant metastatic melanoma and treated by ICI targeting the PD-1 receptor. Follow-up whole-body positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose ([18F]-FDG) was performed at 15 months, and FDG-avid subcutaneous nodules on her legs were detected. A biopsy from a lesion on her right leg was obtained, and histology strongly suggested erythema nodosum. Given the isolated nature of these lesions, the normal serum Angiotensin-Converting Enzyme and the context of ICI, an immune-related sarcoid-like reaction was retained as the most likely diagnosis. Recent literature in immune-oncology suggests that erythema nodosum could be directly related to ICI(s). Although erythema nodosum is a rare occurrence with imaging features overlapping with malignancy, it should be considered in the differential diagnosis of suspicious in-transit metastasis, especially when the patient is treated with ICIs and when lesions follow a bilateral distribution. In conclusion, nuclear medicine physicians should keep in mind this irAE when interpreting PET/CT scans in clinical practice in order to avoid false-positive findings.

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Thouvenot, E., D. Hillaire-Buys, M. A. Bos-Thompson, V. Rigau, L. Durand, B. Guillot, and W. Camu. "Erythema nodosum and glatiramer acetate treatment in relapsing-remitting multiple sclerosis." Multiple Sclerosis Journal 13, no. 7 (August 2007): 941–44. http://dx.doi.org/10.1177/1352458507076385.

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Glatiramer acetate (GA), a well tolerated immunomodulatory treatment for relapsing—remitting multiple sclerosis (RR-MS), consists of a 4-amino acid polymer that mimics the myelin basic protein (MBP). We report the first case of biopsy-proven erythema nodosum (EN) in a patient presenting RR-MS under GA treatment. Comprehensive exams were negative in the search of the etiology of EN, which spontaneously resolved despite treatment continuation. GA treatment is known to generate reactive polyclonal antibodies that can cross-react with myelin epitopes, like MBP. These antibodies may also be implicated in allergenic reactions and auto-immune adverse events, such as anaphylactic shock, lymphadenopathy, livedo-like dermatitis, or lymphocytic infiltration. EN is an unspecific skin reaction occurring in several disorders and induced by many treatments. As EN can result from a polyclonal antibody response or type I hypersensitivity mechanisms, we hypothesize that GA treatment could be responsible for the occurrence of EN. Multiple Sclerosis 2007; 13: 941—944. http://msj.sagepub.com

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Wollina, Uwe, Monika Gruner, and Jaqueline Schönlebe. "Granulomatous tattoo reaction and erythema nodosum in a young woman: common cause or coincidence?" Journal of Cosmetic Dermatology 7, no. 2 (June 2008): 84–88. http://dx.doi.org/10.1111/j.1473-2165.2008.00368.x.

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Suryawati, Nyoman, and Herman Saputra. "Erythema nodosum leprosum presenting as sweet's syndrome-like reaction in a borderline lepromatous leprosy patient." International Journal of Mycobacteriology 7, no. 2 (2018): 191. http://dx.doi.org/10.4103/ijmy.ijmy_49_18.

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Goyal, Tarang, Anupam Varshney, Veena Sharma, and Vijay Zawar. "A rare case of facial annular bullous erythema nodosum leprosum reaction in a young boy." International Journal of Dermatology 55, no. 6 (January 8, 2016): e368-e371. http://dx.doi.org/10.1111/ijd.13221.

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Brandão Neto, Rodrigo Antonio, and Jozélio Freire de Carvalho. "Erythema induratum of Bazin associated with Addison's disease: first description." Sao Paulo Medical Journal 130, no. 6 (2012): 405–8. http://dx.doi.org/10.1590/s1516-31802012000600008.

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CONTEXT: Erythema induratum of Bazin (EIB) is considered to be a tuberculid reaction and consists of recurrent painful nodules. The differential diagnosis includes diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. CASE REPORT: We report the case of a woman with EIB who developed Addison's disease during treatment with anti-tuberculosis drugs with good response to glucocorticoid replacement. The diagnosis was obtained through the clinical picture, positive tuberculin test and positive BCG (bacillus Calmette-Guérin) test on the histological sample. Anti-tuberculosis drugs and glucocorticoid replacement led to disappearance of the signs and symptoms. CONCLUSIONS: This is the first description of an association between EIB and Addison's disease. It should be borne in mind that tuberculosis is an important etiological factor for Addison's disease.

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Kumar, Ajay, Ashish Dalal, Sanjeev Gupta, and Eshita Dadwal. "Erythema nodosum leprosum limited to sun-exposed sites: An unusual presentation of type 2 lepra reaction." Journal of Clinical Sciences 14, no. 2 (2017): 101. http://dx.doi.org/10.4103/2468-6859.204699.

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Nakwan, Narongwit, Sunisa Thaichinda, and Narongsak Nakwan. "A case of erythema nodosum leprosum reaction with diffuse alveolar haemorrhage, successfully treated by pulsed methylprednisolone." Leprosy Review 81, no. 2 (June 1, 2010): 129–36. http://dx.doi.org/10.47276/lr.81.2.129.

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Voorend, Carlijn G. N., and Erik B. Post. "A Systematic Review on the Epidemiological Data of Erythema Nodosum Leprosum, a Type 2 Leprosy Reaction." PLoS Neglected Tropical Diseases 7, no. 10 (October 3, 2013): e2440. http://dx.doi.org/10.1371/journal.pntd.0002440.

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PENG, NAN-JING, JEN-HSIAN WANG, SHIH-PENG HSIEH, GANG-HONG JAO, DAW-GUEY TSAY, and REN-SHYAN LIU. "Ga-67 and Tc-99m HMPAO Labeled WBC Imaging in Erythema Nodosum Leprosum Reaction of Leprosy." Clinical Nuclear Medicine 23, no. 4 (April 1998): 248–50. http://dx.doi.org/10.1097/00003072-199804000-00017.

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DATZ, FREDERICK L. "Erythema Nodosum Leprosum Reaction of Leprosy Causing the Double Stripe Sign on Bone Scan Case Report." Clinical Nuclear Medicine 12, no. 3 (March 1987): 212–14. http://dx.doi.org/10.1097/00003072-198703000-00012.

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43

Eastham, John H., Jack L. Segal, Maria F. Gómez, Gary W. Cole, Magaly Rodríguez De Bittner, and Monique Richer. "Reversal of Erythema Multiforme Major with Cyclophosphamide and Prednisone." Annals of Pharmacotherapy 30, no. 6 (June 1996): 606–7. http://dx.doi.org/10.1177/106002809603000607.

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Objective To report a case of erythema multiforme (EM) major treated with cyclophosphamide and prednisone. Setting General medicine and dermatology consult services, Department of Veterans Affairs Medical Center. Case Summary A 44-year-old man with C4–C5 quadriplegia developed a skin reaction characterized by a painful, generalized maculopapular rash, bullae, ulceronecrotic lesions, and mucosal and epidermal sloughing after taking trimethoprim/sulfamethoxazole. The patient was treated with intravenous cyclophosphamide 150 mg infused over 1 hour every 24 hours and oral prednisone 15 mg every 6 hours. After two doses of cyclophosphamide, formation of bullae and epidermal sloughing had ceased, and the erythema was markedly diminished. Cyclophosphamide was discontinued before the third dose because of evolving leukopenia. Prednisone therapy was continued until the patient was discharged on hospital day 5, at which time the dosage was tapered. Discussion Cyclophosphamide has been used extensively for other dermatologic reactions. Relief of pain and regression of the lesions in our patient occurred more quickly than anticipated. Conclusions Treatment of EM major with cyclophosphamide combined with prednisone appeared to be highly successful in this patient. Cyclophosphamide may be an effective, empiric initial treatment in reversing EM major.

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SEHGAL, V. N., V. SHARMA, and V. K. SHARMA. "The effect of anti-reactional drugs on complement components in the type II, erythema nodosum leprosum, reaction." British Journal of Dermatology 119, no. 2 (August 1988): 255–58. http://dx.doi.org/10.1111/j.1365-2133.1988.tb03209.x.

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Djawad, Khairuddin. "Pentoxifylline therapy for patients with type 2 leprosy reactions: erythema nodosum leprosum in steroid-dependent cases." Vestnik dermatologii i venerologii 97, no. 1 (March 24, 2021): 46–53. http://dx.doi.org/10.25208/vdv1196.

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Introduction. Morbus Hansen is the infectious disease which causes by bacilli intracellular Mycobacterium leprae which mainly affects the skin and peripheral nerves. The leprosy reaction is an episode an immunologically mediated episode of acute or subacute inflammation which affecting skin; nerve; mucous membrane. Type 2 reactions can be last for months and risk of developing dependence on steroids. Pentoxifylline (PTX) works to hampers the production TNF in vitro and in vivo; are an alternative for ENL treatment. Case Report. One case was reported in a male aged 28 years with complaints of recurring red bumps accompanied by fever and pain. Discussion. On physical examination obtained erythema nodosum; with impaired sensibility in the left leg. The patient experienced improvement after being given therapy of neurodex/24 hours/oral; rifampicin 600 mg; ofloxacin 400 mg; minocycline 100 mg which given 3x for a week; and combination therapy to treat the Leprosy reaction given the combination of methylprednisolone 16mg (3-2-0) and Pentoxifylline 400 mg/8 hours/oral. Conclusion. In the 21 day of treatment; the redness lump improved in the middle finger and left arm was gone. No new reddish bumps appeared and less tingling sensation.

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Hasan, Zahidul, Mohammad Rafiqul Mowla, Debashish Mondol Angkur, and Md Ismail Khan. "Efficacy and Safety of Prednisolone Monotherapy Versus Prednisolone Plus Methotrexate in Erythema Nodosum Leprosum (Type 2 Lepra Reaction)." International Journal of Dermatology and Venereology 3, no. 4 (November 12, 2020): 205–10. http://dx.doi.org/10.1097/jd9.0000000000000133.

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Gupta, Nishma, Nallakandy P. Shankernarayan, and Kuppamuthu Dharmalingam. "Serum Proteome of Leprosy Patients Undergoing Erythema Nodosum Leprosum Reaction: Regulation of Expression of the Isoforms of Haptoglobin." Journal of Proteome Research 6, no. 9 (September 2007): 3669–79. http://dx.doi.org/10.1021/pr070223p.

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48

Gunawan, Hendra, Nina Roslina, and Oki Suwarsa. "A case of concomitant subcorneal pustular dermatosis and erythema nodosum leprosum in borderline lepromatous leprosy-relapses." Case Reports in Clinical Pathology 4, no. 4 (November 14, 2017): 6. http://dx.doi.org/10.5430/crcp.v4n4p6.

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Subcorneal pustular dermatosis (SPD) is a rare, chronic, and recurrent pustular eruption characterized histopathologically by subcorneal pustules that contain neutrophils. SPD has been clearly reported conjunction with other diseases. Leprosy reactions are acute inflammatory process that immunologically driven on the chronic course of leprosy. Erythema nodosum leprosum (ENL) is a type II of leprosy reaction putatively can initiate SPD lesions. We report one case of concomitant SPD and ENL in borderline lepromatous leprosy-relapses. A 41-year-old man with the history of using multidrug therapy-multibacillary for leprosy presented with painful erythematous nodules on the trunk and extremities, accompanied by pustules on erythematous base on the face, arms, buttocks, and legs. There were thickening of both ulnar nerves with gloves and stocking hypesthesia. The bacterial index was 3+ and morphological index was 20\%. Histopathological examination on the pustule revealed subcorneal pustules with exocytosis of neutrophils which supported the diagnosis of SPD. A possible immunologic mechanism has been suggested in the induction of the occurence both SPD and ENL.

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Williams, G., E. Kwan, C. N. Giraldo, M. Lincoln, and M. Lewin-Smith. "Panniculitis at the Site of Injection: Infection or Foreign Body Reaction?" American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S29. http://dx.doi.org/10.1093/ajcp/aqaa161.058.

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Abstract Introduction/Objective A 63 year old diabetic female presented to the dermatology clinic with painful abdominal nodules. The nodules seemed to wax and wane every 1–2 weeks and appeared in different locations on the abdomen. The lesions were subcutaneous, tender, firm, and mobile with no discoloration. The patient had diabetes treated with injectable exenatide but no other significant medical or travel history. Methods The differential diagnoses included mycobacterial infection, mechanical insult from injectable diabetes medication, erythema nodosum, erythema induratum, and lupus panniculitis. Ultrasound was indicative of panniculitis. A biopsy of the active lesion was performed. Results The biopsy showed septal and lobular panniculitis with mixed inflammation and multinucleated giant cells. Small, circular, non-polarizable pink amphorous material was associated with the infiltrate. The amphorous material was strongly acid fast. The patient had a negative quantiferon-TB test. Scanning electron microscopy with energy dispersive x-ray analysis showed that the material contained more oxygen and less carbon than surrounding tissue, but no abnormal elements were identified. Infrared spectroscopy of the foreign material most closely matched poly(L- lactide-co-glycolide). Conclusion The diagnosis of exenatide induced granulomatous panniculitis was made. The patient had recently started using this injectable glucagon-like peptide-1 receptor agonist, which has been associated with panniculitis. The injectable formulation is loaded onto microspheres composed of poly (DL-lactic-co-glycolic acid), which is closely related to poly(L-lactide-co-glycolide). This material has been shown to stain strongly acid fast. This case of granulomatous panniculitis due to injectable diabetic medication highlights an important potential pitfall that pathologists should be aware of, especially in cases where mycobacterial infection is in the differential.

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Antunes, Douglas Eulálio, Isabela Maria Bernardes Goulart, Mayara Ingrid Sousa Lima, Patrícia Terra Alves, Paula Cristina Brígido Tavares, and Luiz Ricardo Goulart. "Differential Expression of IFN-γ, IL-10, TLR1, and TLR2 and Their Potential Effects on Downgrading Leprosy Reaction and Erythema Nodosum Leprosum." Journal of Immunology Research 2019 (November 7, 2019): 1–14. http://dx.doi.org/10.1155/2019/3405103.

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Leprosy reactions are acute immunological events that occur during the evolution of chronic infectious disease causing neural damage and disabilities. A study using blood samples of 17 leprosy reaction patients and 17 reaction-free was carried out by means of associations between antigens, receptors, and expression of cytokines, using path analysis providing new insights into the immunological mechanisms involved in triggering leprosy reactions. Toll-like receptors (TLR) such as TLR1 and TLR2, presented balanced expression in the reaction-free multibacillary (MB) group (TLR1: 1.01±0.23, TLR2: 1.22±0.18; p=0.267). On the other hand, downgrading type 1 reaction (T1R) (TLR1: 1.24±0.17, TLR2: 2.88±0.37; p=0.002) and erythema nodosum leprosum (ENL) (TLR1: 1.93±0.17, TLR2: 2.81±0.15; p=0.004) revealed an unbalance in relation to the expression of these receptors. When the path analysis was approached, it was noted that interleukin 10 (IL-10) expression showed a dependence relation with phenolic glycolipid I (PGL-I) in downgrading T1R (direct effect=0.503>residual effect=0.364), whereas in ENL, such relationship occurred with lipoarabinomannan (LAM) (direct effect=0.778>residual effect=0.280). On the contrary, in the reaction-free leprosy group, interferon-gamma (IFN-γ) levels were dependent on the association between TLR2 and TLR1 (0.8735). The high TLR2 expression associated with IL-10 levels, in the leprosy reaction groups, may be hypothetically related to the formation of TLR2/2 homodimers and/or TLR2/6 heterodimers linked to evasion mechanisms in downgrading reactions and pathophysiology of ENL.

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