Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia.

BACKGROUND: Leprosy reactions are a significant cause of morbidity in leprosy population. Erythema nodosum leprosum (ENL) is an immunological complication affecting approximately 50% of patients with lepromatous leprosy (LL) and 10% of borderline lepromatous (BL) leprosy. ENL is associated with clinical features such as skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. ENL is treated mainly with corticosteroids and corticosteroids are often required for extended periods of time which may lead to serious adverse effects. High mortality rate and increased morbidity associated with corticosteroid treatment of ENL has been reported. For improved and evidence-based treatment of ENL, documenting the systems affected by ENL is important. We report here the clinical features of ENL in a cohort of patients with acute ENL who were recruited for a clinico-pathological study before and after prednisolone treatment. MATERIALS AND METHODS: A case-control study was performed at ALERT hospital, Ethiopia. Forty-six LL patients with ENL and 31 non-reactional LL matched controls were enrolled to the study and followed for 28 weeks. Clinical features were systematically documented at three visits (before, during and after predinsolone treatment of ENL cases) using a specifically designed form. Skin biopsy samples were obtained from each patient before and after treatment and used for histopathological investigations to supplement the clinical data. RESULTS: Pain was the most common symptom reported (98%) by patients with ENL. Eighty percent of them had reported skin pain and more than 70% had nerve and joint pain at enrolment. About 40% of the patients developed chronic ENL. Most individuals 95.7% had nodular skin lesions. Over half of patients with ENL had old nerve function impairment (NFI) while 13% had new NFI at enrolment. Facial and limb oedema were present in 60% patients. Regarding pathological findings before treatment, dermal neutrophilic infiltration was noted in 58.8% of patients with ENL compared to 14.3% in LL controls. Only 14.7% patients with ENL had evidence of vasculitis at enrolment. CONCLUSION: In our study, painful nodular skin lesions were present in all ENL patients. Only 58% patients had dermal polymorphonuclear cell infiltration showing that not all clinically confirmed ENL cases have neutrophilic infiltration in lesions. Very few patients had histological evidence of vasculitis. Many patients developed chronic ENL and these patients require inpatient corticosteroid treatment for extended periods which challenges the health service facility in resource poor settings, as well as the patient's quality of life.

Lymph node abscess and cardiac involvement in a patient with nodular lepromatous leprosy (LL) with erythema nodosum leprosum (ENL): a rare occurrence.

With the world's focus on reducing the leprosy patient load to the extent of elimination, finding and reporting the rarer presentations of leprosy becomes important for prompt treatment. Also, these untreated patients may serve as a potential source of infection in community. We report a 35-year old man diagnosed to have lepromatous leprosy and erythema nodosum leprosum with inguinal lymph node abscess and suspected cardiac involvement that proved fatal. We stress the importance of detailed workup to look for associated systemic involvement for timely intervention and favourable outcome.

Histopathology of the lepromatous skin biopsy.

The histopathology of lepromatous skin varies according to the cell-mediated immunity of the host against Mycobacterium leprae. In tuberculoid and borderline tuberculoid leprosy, epithelioid noncaseating granulomas predominate, and acid-fast bacilli (AFB) are absent or only rarely present. In borderline lepromatous and lepromatous leprosy, the infiltrate is composed of macrophages with a vacuolar cytoplasm, lymphocytes, and plasma cells. AFB are numerous. Edema inside and outside the epithelioid granulomas, together with the appearance of large giant cells, are the main features of type 1 reactions. A conspicuous neutrophilic infiltrate in the subcutis with or without vasculitis is found in erythema nodosum leprosum. The main histopathologic features of leprosy and its particular forms are discussed in this review.

In vitro thalidomide does not interfere with the activation of complement by M. leprae.

Erythema nodosum leprosum (ENL) is an inflammatory reaction that may occur in multibacillary leprosy patients, and thalidomide is the treatment of choice. Its cause and the mechanism by which thalidomide suppresses ENL are not known. In the skin lesions, im- mune complexes and split products of complement are found. The activation of complement could precipitate ENL, and thalidomide could suppress the inflammation by inhibiting the activation of complement. To determine if thalidomide could suppress the activation of complement, we first incubated normal serum with thalidomide and with M. leprae or zymosan. The amount of residual functional complement was then assessed by determining the dilution of serum required to lyses sheep erythrocytes sensitized by rabbit antibodies (CH50 Assay). M. leprae and zymosan activated complement. The residual complement activity in the serum incubated with M. leprae or with zymosan was equivalent to that incubated with M. leprae or zymosan in the presence of thalidomide, hydrolyzed thalidomide and metabolites of thalidomide. Thalidomide did not inhibit the activation of complement by zymosan, a known initiator of complement activation by the alternative pathway, or by M. leprae.

Erythema nodosum leprosum in Nepal: a retrospective study of clinical features and response to treatment with prednisolone or thalidomide.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an inflammatory reaction, which may occur in the course of leprosy and may result in nerve function impairment and subsequent disability. METHODS: This retrospective study explores demographic and disease specific parameters. Severity of ENL was assessed using the Reaction Severity Scale (RSS). Records of 94 patients were reviewed. The study reports also on the treatment of 76 of these patients who were treated with prednisolone alone or thalidomide in addition to prednisolone. RESULTS Thirty percent of patients presented with ENL at time of diagnosis; 41% developed ENL-reaction in the first year of MDT. Forty-eight percent of patients were treated for ENL-reaction for less than 12 months; 13% for more than 5 years. High RSS-scores correlated with a longer duration of treatment. In group A (prednisolone) 51.7% and in group B (prednisolone and thalidomide) 76.6% of patients were male. Age, leprosy classification, delay of multidrug treatment (MDT) and interval between MDT and first ENL-symptoms did not differ significantly in both groups. Median duration of ENL-treatment was 15 months in group A versus 38 months in group B (P < 0.001). At the start of treatment, ENL-reaction was less severe in group A (RSS = 12) than in group B (RSS = 18; P = 0.003). DISCUSSION: ENL-symptoms may be of help in the early diagnosis and adequate treatment of ENL. Characterisation of (sub) groups of patients with ENL based on presence and severity of symptoms is important for future prospective studies to better evaluate the efficacy of interventions.

Activation of complement by Mycobacterium leprae requires disruption of the bacilli.

OBJECTIVE: The immune-mediated events that precipitate erythema nodosum leprosum (ENL) are not well understood. One component may be the complexing of antibody with antigens released from infected macrophages, the activation of complement and the subsequent local inflammation. We assess here the ability of highly-purified, disrupted M. leprae, to activate complement. RESULTS: Intact and sonically-disrupted crude and alkali-purified nu/nu mouse-derived M. leprae suspensions were incubated with normal serum and a hemolytic titer (CH50) was determined as a measure of complement fixation. Crude M. leprae consumed complement, and disrupted preparations more than the intact. Purified M. leprae preparations did not consume complement unless disrupted. CONCLUSION: M. leprae, if disrupted, can activate complement. This supports a hypothesis that links released antigens with ENL, and may explain the increased probability of an occurrence of ENL following chemotherapy.

Coccidioidomycosis: a review and update / Coccidioidomycosis: a review and update

Coccidioidomycosis occurs in arid and semi-arid regions of the New World from the western United States to Argentina. Highly endemic areas are present in the southwest United States. Coccidioides species live in the soil and produce pulmonary infection via airborne arthroconidia. The skin may be involved by dissemination of the infection, or by reactive eruptions, such as a generalized exanthem or erythema nodosum. Interstitial granulomatous dermatitis and Sweet's syndrome have recently been recognized as additional reactive signs of the infection. Coccidioidomycosis is a [quot ]great imitator[quot ] with protean manifestations. Cutaneous findings may be helpful clues in the diagnosis of this increasingly important disease.

A study of leprosy reactions in a tertiary hospital in Delhi.

A retrospective study of 531 leprosy patients was undertaken to study the profile of reactions in the post Multi-Drug-Therapy period in a tertiary hospital in Delhi. BT was the most common group. The prevalence of reactions was found to be 8.09% for the Type 1 and 4.70% for the Type 2 reactions for a male:female ratio of 2.2. The Type 1 reaction was most frequently observed in the BB group followed by BL, BT and LL groups respectively. More than half of the patients had reactions at the time of presentation. In only 39.8% of the patients did reaction follow Multi-Drug-Therapy. In 4.5% of the patients with Type 1 reactions (T1R), concomitant infections were noted. The most common presentation of T1R was cutaneous lesions (74.41%) followed by cutaneous lesions and neuritis (53.6%), neuritis alone (12.1%), and only edema of hands and feet (7.31%) respectively. The Type 2 reactions (T2R) presented chiefly as papulo-nodular (92%) lesions followed by pustulonecrotic (8%) lesions. Associated neuritis was found in 40% and periosteitis and iritis in 8% and 4%, respectively. In 8.6% of the patients with T2R, precipitating factors could be observed. The prevalence of deformities in patients with reaction was 25%, and was more common in females. Deformities were observed in 23.25% of the T1R patients and 28% of the T2R patients.

Reaction cases treated at the Regional Leprosy Training and Research Institute, Aska, Orissa: a retrospective analysis.

This study is a retrospective analysis of 147 cases of leprosy reaction selected out of 942 cases of leprosy registered between 1992 and 2002 at the RLTRI, Aska (Orissa). The occurrence of reaction was about 16% with a slight increase over the years. There was a preponderance of males, with about 80% cases among males, and the peak occurrence of reaction was found in the age-group of 21-49 years. Reversal reaction (RR) was seen in 68.7% and ENL in 31.3% of cases. Single episode of RR and ENL reactions was seen in 61.2% and 43.5% respectively. In either type the last episode was seen even after about 32 months after RFT. There was a dissociation between nerve and skin manifestation, with both skin and nerve manifestation in 78.96%, skin lesions only in 21.1% and nerve lesions only in 50.9% of cases. About 88% of reaction was seen in MB patients, with a higher proportion of RR, because of inclusion of more borderline cases. Prednisolone was the drug of choice in both types of reaction, though in 17 cases of steroid dependency, thalidomide was proved to have an edge over steroids. Both types taken together, in half of the cases the first episode of reaction developed within 6 months of starting treatment. Multiple episodes were more common with ENL.

Elevated platelet counts and thrombocytosis in erythema nodosum leprosum

Changes in peripheral blood platelet counts associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing, in each patient, the value obtained on the day thalidomide therapy commenced with the average of the three preceding values. In the 11 patients studied, the mean platelet count rose from 235 to 322 x 10(3)/mm3, p < 0.001. In 3, the platelet count was above the normal limit, qualifying as thrombocytosis, in 7 the rise was appreciable, and in 2 it was negligible. In the 3 patients studied 1-2 weeks after beginning thalidomide, the mean count was 414 x 10(3)/mm3. Counts obtained after 3 or more weeks of thalidomide therapy were within normal limits. This study provided no direct evidence as to the mechanism responsible for the elevated platelet count, but mediation by interleukin-6 (IL-6) was concluded to be an attractive hypothesis, consistent with prior studies of IL-6 in reactive thrombocytosis and of IL-6 in ENL.

Decreases in mean hemoglobin and serum albumin values in erythema nodosum leprosum and lepromatous leprosy.

Changes in hemoglobin (HGB) and serum albumin (SA) concentration associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing the values obtained on the day thalidomide or prednisone therapy commenced, with each patients' preceding values. In three groups of ENL patients mean HGB values fell with statistical significance: 1) in 38 patients who had been begun on thalidomide in the decade of the 1990s and who had been receiving dapsone for a minimum of 6 months, mean HGB values fell from 13.19 gm/dl to 12.27 gm/dl, or 7.0%, p = 6.0 x 10(-6); 2) in 8 patients who were in the active patient file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean HGB values feel from 13.40 gm/dl to 11.96 gm/dl, or 10.7%, p = 0.0015; and 3) in 8 patients not overlapping with the preceding groups, who were treated with rifampin and minocylcine or clarithromycin mean HGB values fell from 13.25 gm/dl to 12.48 gm/dl, or 5.8%, p = 0.0035. In two groups of ENL patients SA values also fell with statistical significance: 1) in 34 patients who were begun on thalidomide in the decade of the 1990s and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.14 gm/dl to 3.77 gm/dl, or 8.9%, p = 1.2 x 10(-5); and 2) in 10 patients from the active file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.45 gm/dl to 4.06 gm/dl, or 8.8%, p = 0.039. A brisk fall in HGB values was often accompanied by a fall in SA concentration, and vice versa. Recovery from extreme falls in HGB and SA values was complete in 13 weeks. Recovery occurred in the presence of continued dapsone treatment. The falls could be rapid, occurring too soon to be the result of decreased erythropoiesis or hepatic SA synthesis. This study provides no direct evidence as to the mechanism responsible for the fall in these two parameters, but an interleukin-6 mediated hemodilution is an attractive hypothesis. The ENL-associated fall in HGB values was distinct from dapsone-induced hemolysis and the anemia of chronic disease. The ENL-associated anemia is not a good reason to discontinue dapsone therapy.

Risk Factor for erythema nodosum leprosum

A retrospective study of new borderline lepromatous and lepromatous patients reporting for multidrug therapy (MDT) for leprosy at the Anandaban Leprosy Hospital, Kathmandu, Nepal, over an 8-year period was conducted to determine the prevalence of erythema nodosum leprosum (ENL), the time and frequency of reactions, and clinical and laboratory parameters associated with ENL. An overall prevalence of ENL in this cohort of 19% was found. One third of these reactions occurred in patients before MDT was given, one third in the first 6 months and one third after 6 months of treatment. Nearly 1 in 10 of the ENL reactions occurred in patients who had completed 2 years of MDT; 45% of patients with ENL had more than one episode. Data collected at the patients' first presentation was used to identify four major risk factors. Patients with lepromatous disease, skin infiltration or a bacterial index (BI) of > 4+ were at significantly increased risk. Patients older than 40 were at significantly decreased risk of ENL. There was a linear relationship in the risk of ENL with an increasing BI and an inverse relationship to increasing age. These observations should enable clinicians to recognize patients at first presentation who will be likely to develop ENL.