Recurrent Erythema Nodosum Leprosum Research Articles

Type 2 reaction associated sensorineural hearing loss in a drug resistant lepromatous leprosy patient: A case report

Rationale: Leprosy, a chronic granulomatous disease often present clinically as erythema nodosum leprosum, a type 2 reaction. The involvement of cochlear part of audiovestibular system is a rarity. Patient concerns: A 26-year-old male patient with lepromatous leprosy developed bilateral sensorineural hearing loss (SNHL) during type 2 reactional episode. Diagnosis: Recurrent erythema nodosum leprosum in rifampicin-resistant lepromatous leprosy. Interventions: Corticosteroids and second-line multidrug therapy. Outcomes: The patient improved significantly and was further referred for management of psychosocial impact due to sensorineural hearing loss. Lessons: The hearing impairment is a rare complication of type 2 reaction. Any patient with suspected cranial nerve involvement should essentially be screened by tuning fork tests for early detection of hearing impairment and offer timely intervention as required. All high bacteriological index cases should be investigated for antimicrobial resistance in high endemic areas.

A real-world study of low-dose thalidomide in severe erythema nodosum leprosum highlighting its mechanistic rationale in a resource-constrained target population.

Corticosteroids remain the main therapy in erythema nodosum leprosum (ENL), and long-term usage in chronic or recurrent ENL is a cause of significant morbidity and mortality. Thalidomide exerts dramatic effect in controlling ENL and helps reduce the dose of steroids, but the cost is a hindrance to its usage. Patients of ENL (steroid naïve and steroid-dependent) were recruited over a 1-year period. An escalating dose of low-dose thalidomide with a reducing dose of prednisolone was titrated depending on the control of disease activity. The primary aim was to reduce the dose of steroids to the lowest effective dose, and the secondary aim was to stop. Sixteen patients of ENL were studied (mean duration of ENL 22.1 months, 15 severe ENL), and a majority (11/16, 68%) were on steroids with a mean duration of 11.27 months. All patients had steroid-related side effects (cushingoid habitus 81.8%, weight gain 54.5%, diabetes mellitus 9%, hyperlipidemia 18.18%, cataract 18.1%, osteoporosis 36.3%, striae 36.3%, acneiform eruptions 18.1%, and myopathy 9%). Steroids could be tapered in a majority of patients (n = 9) within 3 months (mean 2.44 months) with a low dose of thalidomide (25-150 mg/day, mean 78.3 mg) achieving a significant reduction in prednisolone dose (33.16 mg at baseline; 4.28 mg at 3 months, P < 0.05). Steroids could be stopped in 92% of patients by 3.03 months, and both drugs could be stopped in 80% of cases by 5.83 months. The rapid and effective control of ENL with low-dose thalidomide in our series is comparable to the historical efficacy of high-dose thalidomide regimens, making it an affordable therapy in resource-constrained settings and an excellent steroid-sparing agent. The rapid onset of disease control is likely attributable to its action via neutrophils.

Thalidomide and steroid in the management of erythema nodosum leprosum.

OBJECTIVE:The objective of the study was to assess the efficacy and safety profiles of combined treatment of prednisolone with thalidomide (Gr-A) and prednisolone with clofazimine (Gr. B) in patients with erythema nodosum leprosum (ENL) or type 2 lepra reactions.MATERIALS AND METHODS:Efficacy of both regimens was assessed on the basis of clinical recovery of recurrent ENL measured by reaction severity score (RSS), Visual Analog Scale (VAS), and recurrence of type 2 lepra reaction. The causality assessment of adverse drug reactions was done using the WHO UMC causality assessment scale.RESULTS:The average age of patients with recurrent ENL was 42.8 years (male) and 51.8yrs (female) and had mean duration of leprosy and recurrent ENL 2.4 years and 2.09 years, respectively. 80% of nonrecurrence was observed in Gr-A versus 66% in Gr-B. Significant (P < 0.05) lower RSS and VAS was found in both the treatment groups as compared to pretreatment value. The reduction in RSS and VAS was statistically significant (P < 0.05) in Gr-A compared to Gr-B treatment.CONCLUSION:Thalidomide combination with steroid was found to be more efficacious than clofazimine combination with steroid in the treatment of ENL both the treatment regimens showed few tolerable side effects. Improved strategies for the treatment and management of these reactions need to be developed.

Comparison of the efficacy and safety of minocycline and clofazimine in chronic and recurrent erythema nodosum leprosum—A randomized clinical trial

Management of chronic/recurrent erythema nodosum leprosum (ENL) is challenging. The majority of these patients become steroid-dependent and suffer from the adverse effects of long-term corticosteroid use. Minocycline has shown promising results in a small series of chronic/recurrent ENL patients. The aim of this study was to compare the efficacy and safety of minocycline and clofazimine in patients with chronic/recurrent ENL. In this prospective randomized clinical trial, 60 participants with chronic/recurrent ENL were randomized (1:1) to receive either minocycline 100 mg once daily or clofazimine 100 mg thrice daily for 12 weeks along with prednisolone according to WHO protocol and followed up for 6months. The outcome measures were mean time for initial control of ENL, proportion of patients having a recurrence of ENL, mean time for recurrence after initial control, additional prednisolone requirement, and frequency of adverse events. Initial control of ENL was achieved earlier in the minocycline group as compared to the clofazimine group (2.97 ± 1.9 weeks vs. 4 ± 1.96 weeks, respectively; p-0.048). The number of participants having ENL flares/recurrences during the study period was comparable in both groups (71.4% in clofazimine vs. 55.2% in minocycline group; p-0.2). The participants in the minocycline group remained in remission for a longer duration after initial control of ENL as compared to the clofazimine group (p-0.001). Mean additional prednisolone dose required for control of ENL flares/recurrences was also comparable in both groups (p-0.09). The minocycline group had fewer side effects than the clofazimine group (p-0.047). Minocycline led to a rapid and sustained improvement of ENL episodes with fewer adverse events showing a superior efficacy to clofazimine.

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights.

Erythema nodosum leprosum (ENL), also known as type 2 reaction (T2R) is an immune complex mediated (type III hypersensitivity) reactional state encountered in patients with borderline lepromatous and lepromatous leprosy (BL and LL) either before, during, or after the institution of anti-leprosy treatment (ALT). The consequences of ENL may be serious, leading to permanent nerve damage and deformities, constituting a major cause of leprosy-related morbidity. The incidence of ENL is increasing with the increasing number of multibacillary cases. Although the diagnosis of ENL is not difficult to make for physicians involved in the care of leprosy patients, its management continues to be a most challenging aspect of the leprosy eradication program: the chronic and recurrent painful skin lesions, neuritis, and organ involvement necessitates prolonged treatment with prednisolone, thalidomide, and anti-inflammatory and immunosuppressive drugs, which further adds to the existing morbidity. In addition, the use of immunosuppressants like methotrexate, azathioprine, cyclosporine, or biologics carries a risk of reactivation of persisters (Mycobacterium leprae), apart from their own end-organ toxicities. Most ENL therapeutic guidelines are primarily designed for acute episodes and there is scarcity of literature on management of patients with chronic and recurrent ENL. It is difficult to predict which patients will develop chronic or recurrent ENL and plan the treatment accordingly. We need simple point-of-care or ELISA-based tests from blood or skin biopsy samples, which can help us in identifying patients who are likely to require prolonged treatment and also inform us about the prognosis of reactions so that appropriate therapy may be started and continued for better ENL control in such patients. There is a significant unmet need for research for better understanding the immunopathogenesis of, and biomarkers for, ENL to improve clinical stratification and therapeutics. In this review we will discuss the potential of neutrophils (polymorphonuclear granulocytes) as putative diagnostic and prognostic biomarkers by virtue of their universal abundance in human blood, functional versatility, phenotypic heterogeneity, metabolic plasticity, differential hierarchical cytoplasmic granule mobilization, and their ability to form NETs (neutrophil extracellular traps). We will touch upon the various aspects of neutrophil biology relevant to ENL pathophysiology in a step-wise manner. We also hypothesize about an element of metabolic reprogramming of neutrophils by M. leprae that could be investigated and exploited for biomarker discovery. In the end, a potential role for neutrophil derived exosomes as a novel biomarker for ENL will also be explored.

Conundrum of recurrent erythema nodosum leprosum and dapsone hypersensitivity syndrome complicating pediatric leprosy

Introduction: Leprosy, a chronic infectious disease affecting the skin and peripheral nerves, has been considered a disease of adults due to its long incubation period, but in endemic regions like the Indian subcontinent, pediatric leprosy cases continue to rise reflecting active disease transmission in the community. Case report: We describe a case of bordeline lepromatous leprosy in a child complicated by severe type 2 lepra reaction and dapsone hypersensitivity syndrome. Conclusion: Pediatric leprosy cases though commonly paucibacillary, can also present with a high bacillary burden. Complicated leprosy cases need nuanced care and highlight the importance of adequate clinical exposure to leprosy cases, so that such cases can be confidently managed.

Experiences with Thalidomide for Erythema Nodosum Leprosum– a retrospective study

Thalidomide is well known as a steroid sparing drug in Erythema Nodosum leprosum (ENL) reaction in leprosy. There is no guideline as to when it should be offered to patients. Documentation of ENL presentation with its morbidity before and after with patient profile can be a baseline to develop a selection criteria as to when thalidomide should be started to reduce steroid related morbidly. Chart and electronic record review was done. 427 ENL patients attended the hospital from 2010 to 2014. 73 patients (67 males six females) were treated with thalidomide. 77% (56) patients were in the age group of 16–45 yrs. 16% (12) were dependent and 39% (29) were taking steroids at presentation. 82% (60) became dependent while on treatment. Ninety five percent were chronic or recurrent ENLs and 73% (53) had moderate to severe ENLs over 49 median months. Steroid induced morbidities were (Cushingoid features 42%, diabetes 21%, infections GI 42%, genitourinary 26%, cataract 23%). There was 11% mortality. Further studies are recommended to diagnose steroid dependence early to prevent serious adverse effects.

Hypnotherapy: A useful adjunctive therapeutic modality in hansen′s disease

Hypnotherapy is a useful adjunctive psychotherapeutic procedure used in various conditions such as pain disorders, atopic dermatitis, and alopecia areata. However, it is less utilized in the field of dermatology. Only limited data exist on its role in the management of various skin diseases. There is dearth of literature on the role of hypnotherapy in Hansen's disease (HD). We report two cases of HD, one with very resistant neuralgia and the other with recurrent erythema nodosum leprosum (ENL). Both the patients were assessed using hospital anxiety and depression scale, dermatology life quality index and the neuralgia was assessed using the visual analog scale. Three sessions of hypnotherapy were given to both the patients. There was dramatic improvement in the incidence of ENL and neuralgia and we could rapidly reduce the dose of drugs used for both conditions.

Deep Vein Thrombosis in A Patient with Lepromatous Leprosy Receiving Thalidomide to Treat Leprosy Reaction

Thalidomide is the treatment of choice for severe or recurrent erythema nodosum leprosum. Its use has been associated with deep vein thrombosis in patients with blood disorders, however, particularly when used in combination with corticosteroids or chemotherapy. We describe a case of deep vein thrombosis in a 43-year-old man with lepromatous leprosy who was being treated with thalidomide and prednisone for a type 2 leprosy reaction (erythema nodosum leprosum); the patient also had transiently positive antiphospholipid antibody results. We stress the importance of considering deep vein thrombosis, a potentially fatal complication, in dermatology patients treated with thalidomide.

Trombosis venosa profunda en paciente con lepra lepromatosa tratado con talidomida por leprorreacción

Thalidomide is the treatment of choice for severe or recurrent erythema nodosum leprosum. Its use has been associated with deep vein thrombosis in patients with blood disorders, however, particularly when used in combination with corticosteroids or chemotherapy. We describe a case of deep vein thrombosis in a 43-year-old man with lepromatous leprosy who was being treated with thalidomide and prednisone for a type 2 leprosy reaction (erythema nodosum leprosum); the patient also had transiently positive antiphospholipid antibody results. We stress the importance of considering deep vein thrombosis, a potentially fatal complication, in dermatology patients treated with thalidomide.

Thalidomide: An experience in therapeutic outcome and adverse reactions

Background: The US FDA‐approved thalidomide for the treatment of chronic recurrent/severe erythema nodosum leprosum. Thalidomide is also useful in many other inflammatory dermatological conditions where patients have exhausted other treatment options. Methods: The beneficial and adverse clinical effects of thalidomide were studied in 25 patients suffering from different inflammatory dermatological conditions that were poorly controlled with conventional therapies. Results: Thalidomide was found to be effective in various inflammatory dermatological diseases other than chronic recurrent erythema nodosum leprosum such as Behçet's disease, disseminated and hypertrophic discoid lupus erythematosus, erosive lichen planus, discoid lupus erythematosus‐lichen planus overlap, recurrent aphthous stomatitis and prurigo nodularis. Deep vein thrombosis due to thalidomide occurred in 20% of these patients and appears to be a significant side effect. Conclusion: Thalidomide appears promising in a number of inflammatory dermatological conditions and will probably find new usages in future. The treating physicians need to be wary of the thrombo‐embolic complications due to thalidomide especially when glucocorticoids or other chemotherapeutic agents such as doxorubicin, gemcitabine, 5‐fluorouracil or dexamethasone‐cyclophosphamide pulse therapy are being used concomitantly, and in patients of metastatic renal carcinoma, myelodysplastic syndrome or multiple myeloma receiving thalidomide/chemotherapy. Antiphospholipid or anticardiolipin antibodies appear to be other possible risk factors for this complication.

Role of azathioprine in preventing recurrences in a patient of recurrent erythema nodosum leprosum

The pathogenesis of erythema nodosum leprosum (ENL) involves both immune complex deposition and dysfunction of cell mediated immunity. Tumour necrosis factor-alpha (TNF-alpha) plays an important role in its pathogenesis. Thalidomide and corticosteroids are the mainstay of treatment for ENL. However, there are often severe limitations to their use. We report a case of recurrent ENL treated successfully with azathioprine. A 15-year-old unmarried girl with lepromatous leprosy had recurrent ENL for 2 years. She was treated with WHO-MB MDT and prednisolone in doses of 40-90 mg a day for 2-12 weeks. Her condition was inadequately controlled. The patient was therefore treated with thalidomide 300 mg and prednisolone 40 mg. The symptoms subsided after 5 days and ENL lesions healed in 2 weeks. Prednisolone was reduced by 10 mg per week and stopped, while thalidomide was reduced to 100 twice daily after 4 weeks. Azathioprine 100 mg (2 mg/kg per day) daily orally was added to prevent recurrences. Thalidomide was further reduced and stopped after another 4 weeks while she continued with azathioprine in the same doses for 8 months. There was no recurrence of ENL lesions and no side effects of the therapy. MB-MDT was stopped 1 year ago, and she is on follow-up without any relapse. Azathioprine, therefore, appears to be an effective and safe drug to prevent recurrences of ENL.

Treatment of Recurrent Erythema Nodosum Leprosum with Infliximab

To the Editor: A 52-year-old woman with multibacillary (borderline lepromatous) leprosy, who had been treated intermittently with dapsone since 1965, presented to our department in 1996 with active...

Bullous erythema nodosum leprosum (bullous type 2 reaction)

A 35-year-old man suffering from lepromatous leprosy with recurrent erythema nodosum leprosum (ENL) (bullous type 2 reaction) was admitted for acute exacerbation of the reaction. He had received regular WHO multibacillary multidrug therapy (WHO-MB-MDT) and corticosteroids for 11 months. The dose of corticosteroids could not be tapered below 20 mg/day due to sudden, frequent, and severe relapses of ENL. In hospital, he suddenly developed hypotension for which he was moved to the intensive care unit and managed. On the third day, he developed multiple, flaccid and tense bullae, some of which were hemorrhagic, over the face, trunk, and proximal extremities (Fig. 1). Some of the ENL lesions showed a central bluish hue. Investigations revealed leukocytosis, thrombocytopenia, and hypokalemia. Blood culture yielded coagulase-negative Staphylococcus aureus. Slit skin smear and smear from the blister fluid showed numerous, fragmented, acid-fast bacilli (AFB) in clusters and many neutrophils (Fig. 2). Skin biopsy revealed a subepidermal bulla that consisted of neutrophils and macrophage granulomas in the dermis together with perivascular neutrophilic infiltration (Fig. 3); however, there were no features suggestive of vasculitis. Fite's stain demonstrated fragmented AFB. Both direct and indirect immunofluorescence studies did not show features of autoimmune bullous disorders; however, moderately strong discontinuous fibrinogen deposits were seen along the basement membrane and around the blood vessels. There were no deposits of immunoglobulin G (IgG) and C3. He was treated with antimicrobials, potassium chloride, and hydrocortisone, 100 mg intravenously, twice daily, which was subsequently switched to oral prednisolone. He responded well and was discharged. Upon lowering the dose of corticosteroids, he again developed severe ENL with fewer bullous lesions. Figure Figure 1 Open in figure viewerPowerPoint Multiple, tense, hemorrhagic bullae over the trunk Figure 2Open in figure viewerPowerPoint Smear from the blister fluid showing numerous, fragmented, acid-fast bacilli (AFB) and neutrophils (Ziehl–Neelsen stain, × 200) Figure 3Open in figure viewerPowerPoint Photomicrograph of the skin biopsy showing subepidermal bulla consisting of neutrophils and macrophage granulomas in the dermis together with perivascular neutrophilic infiltration (hematoxylin and eosin, × 200)

Bullous erythema nodosum leprosum (bullous type 2 reaction)

A 35‐year‐old man suffering from lepromatous leprosy with recurrent erythema nodosum leprosum (ENL) (bullous type 2 reaction) was admitted for acute exacerbation of the reaction. He had received regular WHO multibacillary multidrug therapy (WHO‐MB‐MDT) and corticosteroids for 11 months. The dose of corticosteroids could not be tapered below 20 mg/day due to sudden, frequent, and severe relapses of ENL. In hospital, he suddenly developed hypotension for which he was moved to the intensive care unit and managed. On the third day, he developed multiple, flaccid and tense bullae, some of which were hemorrhagic, over the face, trunk, and proximal extremities (Fig. 1). Some of the ENL lesions showed a central bluish hue. Investigations revealed leukocytosis, thrombocytopenia, and hypokalemia. Blood culture yielded coagulase‐negative Staphylococcus aureus. Slit skin smear and smear from the blister fluid showed numerous, fragmented, acid‐fast bacilli (AFB) in clusters and many neutrophils (Fig. 2). Skin biopsy revealed a subepidermal bulla that consisted of neutrophils and macrophage granulomas in the dermis together with perivascular neutrophilic infiltration (Fig. 3); however, there were no features suggestive of vasculitis. Fite's stain demonstrated fragmented AFB. Both direct and indirect immunofluorescence studies did not show features of autoimmune bullous disorders; however, moderately strong discontinuous fibrinogen deposits were seen along the basement membrane and around the blood vessels. There were no deposits of immunoglobulin G (IgG) and C3. He was treated with antimicrobials, potassium chloride, and hydrocortisone, 100 mg intravenously, twice daily, which was subsequently switched to oral prednisolone. He responded well and was discharged. Upon lowering the dose of corticosteroids, he again developed severe ENL with fewer bullous lesions.Multiple, tense, hemorrhagic bullae over the trunkimageSmear from the blister fluid showing numerous, fragmented, acid‐fast bacilli (AFB) and neutrophils (Ziehl–Neelsen stain, × 200)imagePhotomicrograph of the skin biopsy showing subepidermal bulla consisting of neutrophils and macrophage granulomas in the dermis together with perivascular neutrophilic infiltration (hematoxylin and eosin, × 200)image

Renal lesions in leprosy: A retrospective study of 199 autopsies

In the present work, 199 patients with leprosy who underwent autopsy between 1970 and 1986 were retrospectively studied to determine the prevalence, types, clinical characteristics, and etiologic factors of renal lesions (RLs) in leprosy. Patients were divided into two groups: 144 patients with RLs (RL+) and 55 patients without RLs (RL−). RLs observed in 72% of the autopsied patients were amyloidosis (AMY) in 61 patients (31%), glomerulonephritis (GN) in 29 patients (14%), nephrosclerosis (NPS) in 22 patients (11%), tubulointerstitial nephritis (TIN) in 18 patients (9%), granuloma in 2 patients (1%), and other lesions in 12 patients (6%). AMY occurred most frequently in patients with lepromatous leprosy (36%; nonlepromatous leprosy, 5%; P < 0.01), recurrent erythema nodosum leprosum (33%; P < 0.02), and trophic ulcers (27%; 0.05 < P < 0.10). Ninety-seven percent of AMY was found in patients with lepromatous leprosy, 88% showed recurrent trophic ulcers, and 76% presented with erythema nodosum leprosum. NPS was found in older patients with arterial hypertension, neoplastic diseases, infectious diseases, and vasculitis associated with GN. Most patients with AMY presented with proteinuria (95%) and renal failure (88%). The most frequent causes of death were renal failure in patients with AMY (57%), infectious diseases in patients with GN (41%) and TIN (45%), and cardiovascular diseases in patients with NPS (41%). No difference in survival rates was observedamong RL− patients and those with AMY, GN, NPS, or TIN. © 2001 by the National Kidney Foundation, Inc.

Rapidly progressive (crescentric) glomerulonephritis in erythema nodosum leprosum: case report

A middle aged man (48 years) with short duration of illness (7 days) was admitted in the state of acute renal failure with erythema nodosum leprosum. He had repeated episodes of erythema nodosum leprosum in the past. His blood pressure was normal (150/80 mm Hg). During his hospital stay he was in the state of progressive anaemia (Hb = 8.8 g/dl to 7.2 g/dl), oliguria (urine out-put = 250-350 ml/day), azotaemia (blood urea = 198 mg/d1 to 218 mg/dl) and impaired renal function tests with fatal outcome. Kidneys were smooth, congested and weighing 150 g each with histological features of rapidly progressive (crescentric) glomerulonephritis, a result of immune complex deposition from recurrent erythema nodosum leprosum episodes.

Patterns of neurological involvement in relation to chronic and-or recurrent erythema nodosum leprosum.

Patterns of neurological involvement in relation to chronic and-or recurrent erythema nodosum leprosum.