Ulcers in leprosy patients, an unrecognized clinical manifestation: a report of 8 cases.

BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. It is a polymorphic disease with a wide range of cutaneous and neural manifestations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neuropathies. CASES PRESENTATION: We report eight patients with multibacillary leprosy who presented specific skin ulcers as part of their main leprosy manifestation. Ulcers were mostly present on lower limbs (eight patients), followed by the upper limbs (three patients), and the abdomen (one patient). Mean time from onset of skin ulcers to diagnosis of leprosy was 17.4 months: all patients were either misdiagnosed or had delayed diagnosis, with seven of them presenting grade 2 disability by the time of the diagnosis. Reactional states, LP or neuropathy as potential causes of ulcers were ruled out. Biopsy of the ulcer was available in seven patients: histopathology showed mild to moderate lympho-histiocytic infiltrate with vacuolized histiocytes and intact isolated and grouped acid-fast bacilli. Eosinophils, vasculitis, vasculopathy or signs of chronic venous insufficiency were not observed. Skin lesions improved rapidly after multidrug therapy, without any concomitant specific treatment for ulcers. CONCLUSIONS: This series of cases highlights the importance of recognizing ulcers as a specific cutaneous manifestation of leprosy, allowing diagnosis and treatment of the disease, and therefore avoiding development of disabilities and persistence of the transmission chain of M. leprae.

Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia.

BACKGROUND: The clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R). METHODS: History or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants. RESULTS: There are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018). CONCLUSIONS: Our results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions.

Association of viable Mycobacterium leprae with Type 1 reaction in leprosy.

UNLABELLED: The working hypothesis is that, viable Mycobacterium leprae (M. leprae) play a crucial role in the precipitation of Type 1 reaction (T1R) in leprosy. MATERIAL AND METHODS: A total of 165 new multibacillary patients were studied. To demonstrate presence of viable M. leprae in reactional lesion (T1R+), three tests were used concurrently viz. growth in the mouse foot pad (MFP), immunohistochemical detection of M. leprae secretory protein Ag85, and 16s rRNA--using in situ RT-PCR. Mirror biopsies and non reactional lesions served as controls (T1R-). FINDINGS: A significantly higher proportion of lesion biopsy homogenates obtained at onset, from T1R(+) cases have shown unequivocal growth in MFP, proving the presence of viable bacteria, as compared to T1R(-) (P < 0.005). In contrast, few Mirror biopsies were positive in both T1R(+) and T1R(-). With respect to Ag85, while the overall positivity was higher in T1R(+) (74%), however the intensity of staining (Grade 2+) was disproportionately higher in T1R(+) BT-BB lesions 11/20 (55%). In the rebiopsies obtained during a repeat episode of T1R, Ag 85 as well as 16s rRNA, positivity (62% & 100%) was higher in T1R(+). It is inferred therefore 'viable' bacteria are an essential component in T1R and difference in the quality of bacilli, not the quantity or the ratio of dead to viable play a role in the precipitation of T1R. In conclusion, the findings show that 'metabolically active' M. leprae is a component/prerequisite and the secretory protein Ag 85, might be the trigger for precipitation of T1R.

Chromoblastomycosis in a resident of a leprosarium.

Chromoblastomycosis is caused by dematiaceous fungi. It develops after inoculation of the organism into the skin. The lesion begins as a pink, scaly papule or warty growth. We report a case of chromoblastomycosis occurring in a multibacillary leprosy patient, who had already been released from treatment (RFT). The diagnosis was confirmed by the presence of sclerotic bodies (Medlar bodies/copper penny bodies). Systemic antifungal treatment has been found effective. The case is being reported in view of the association of two diseases and the dramatic clinical response to systemic treatment with Itraconazole.

Ileofemoral Deep Vein Thrombosis (DVT) in Steroid Treated Lepra Type 2 Reaction Patient.

In 1998 a 57-year-old man having skin leisons of 6 months duration reported to Central Leprosy Teaching and Research Institute (CLTRI), Chengalpattu. It was diagnosed as a case of borderline lepromatous leprosy with a type 2 lepra reaction, was treated with multi bacillary-multi drug therapy (MBMDT) for a period of 12 months and the patient was released from treatment (RFT) in September 1999. For reactions the patient was treated with prednisolone for more than 10 months. After 14 years in April 2013 the same patient presented to CLTRI with complaints of weakness of both hands with loss of sensation for 4 months, so making a diagnosis suggestive of MB relapse with neuritis the patient was started with MB-MDT for period of 12 months with initial prednisolone 25 mg OD dose then increased to 40 mg for painful swollen leg and to follow the neuritis associated pain and swelling. Increased dose is not beneficial and the patient was investigated for other pathology. Doppler ultra-sound revealed a left ileofemoral deep vein thrombosis (DVT) in that patient with levels. Prednisolone was withdrawn and the patient was started with anticoagulant heparin followed by warfarin. During this period rifampicin was also withdrawn. After patient was in good condition he was put on MB-MDT regimen. Till the 6th pulse the patient continues to show improvement in functions without steroids and any tenderness, he is taking multivitamins; regular physiotherapy. This DVT appears to be due to prednisolone and such causative relationship though rare should be kept in mind when patient on long term treatment with steroids/and or immobilized or on prolonged bed rest report with such symptomatology.

Dapsone and body mass index in subjects with multibacillary leprosy.

BACKGROUND: The physiological changes in obese subjects can modify the pharmacokinetic profiles of drugs influencing the therapeutic efficacy. METHODS: In this study, the authors compare plasma dapsone trough levels of multibacillary leprosy subjects stratified by body mass index (BMI) to evaluate if obesity plays a significant role on drug levels. The relationship between drug levels and BMI was also determined. Dapsone was measured by high-performance liquid chromatography and BMI based on World Health Organization criteria. RESULTS: At steady state, the median plasma dapsone trough level was significantly lower in obesity class 2 group, when compared with other groups, but they were similar between normal weight and preobesity groups. A weak association between drug levels and BMI was observed. CONCLUSIONS: Obesity promotes a significant reduction in plasma dapsone trough levels of subjects with multibacillary leprosy with a weak association between drug levels and BMI.

Progression of leprosy disability after discharge: is multidrug therapy enough?

OBJECTIVE: To evaluate the risk factors related to worsening of physical disabilities after treatment discharge among patients with leprosy administered 12 consecutive monthly doses of multidrug therapy (MDT/WHO). METHODS: Cohort study was carried out at the Leprosy Laboratory in Rio de Janeiro, Brazil. We evaluated patients with multibacillary leprosy treated (MDT/WHO) between 1997 and 2007. The Cox proportional hazards model was used to estimate the relationship between the onset of physical disabilities after release from treatment and epidemiological and clinical characteristics. RESULTS: The total observation time period for the 368 patients was 1 570 person-years (PY), averaging 4.3 years per patient. The overall incidence rate of worsening of disability was 6.5/100 PY. Among those who began treatment with no disability, the incidence rate of physical disability was 4.5/100 PY. Among those who started treatment with Grade 1 or 2 disabilities, the incidence rate of deterioration was 10.5/100 PY. The survival analysis evidenced that when disability grade was 1, the risk was 1.61 (95% CI: 1.02-2.56), when disability was 2, the risk was 2.37 (95% CI 1.35-4.16), and when the number of skin lesions was 15 or more, an HR = 1.97 (95% CI: 1.07-3.63). Patients with neuritis showed a 65% increased risk of worsening of disability (HR = 1.65 [95% CI: 1.08-2.52]). CONCLUSION: Impairment at diagnosis was the main risk factor for neurological worsening after treatment/MDT. Early diagnosis and prompt treatment of reactional episodes remain the main means of preventing physical disabilities.

Using methotrexate to treat patients with ENL unresponsive to steroids and clofazimine: a report on 9 patients.

UNLABELLED: Erythema nodosum leprosum (ENL) is a chronic recurrent systemic complication of multi-bacillary leprosy frequently associated with the development of neuritis, iritis, orchitis, arthritis and dactylitis. It is well managed by thalidomide, but thalidomide is not available in Bangladesh. The World Health Organization recommends high doses of clofazimine and prednisolone. About 19% of patients do not respond completely to this regimen or experience relapse when reducing steroid dosage. OBJECTIVE: We undertook this study to determine whether oral prednisolone combined with methotrexate was an effective and safe treatment regimen for individuals with ENL resistant to clofazimine and prednisolone. METHODOLOGY: Between September, 2006-June, 2011, we treated nine resistant ENL patients with a combination of prednisolone and methotrexate for 24-36 months with a mean duration of 30 months. RESULT: We observed improvement leading to persistent remission of ENL in all our patients. Adverse effects were mild weight gain, weight gain with facial swelling, folliculitis and extensive Pityriasis versicolor infection in one patient and crusted scabies in another. CONCLUSION: A combination of prednisolone and methotrexate was safe and effective in managing ENL not controlled by clofazimine and prednisolone.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Increased hepcidin expression in multibacillary leprosy.

Iron is essential for all organisms and its availability can control the growth of microorganisms; therefore, we examined the role of iron metabolism in multibacillary (MB) leprosy, focusing on the involvement of hepcidin. Erythrograms, iron metabolism parameters, pro-inflammatory cytokines and urinary hepcidin levels were evaluated in patients with MB and matched control subjects. Hepcidin expression in MB lesions was evaluated by quantitative polymerase chain reaction. The expression of ferroportin and hepcidin was evaluated by immunofluorescence in paucibacillary and MB lesions. Analysis of hepcidin protein levels in urine and of hepcidin mRNA and protein levels in leprosy lesions and skin biopsies from healthy control subjects showed elevated hepcidin levels in MB patients. Decreases in haematologic parameters and total iron binding capacity were observed in patients with MB leprosy. Moreover, interleukin-1 beta, ferritin, soluble transferrin receptor and soluble transferrin receptor/log ferritin index values were increased in leprosy patients. Hepcidin was elevated in lepromatous lesions, whereas ferroportin was more abundant in tuberculoid lesions. In addition, hepcidin and ferroportin were not colocalised in the biopsies from leprosy lesions. Anaemia was not commonly observed in patients with MB; however, the observed changes in haematologic parameters indicating altered iron metabolism appeared to result from a mixture of anaemia of inflammation and iron deficiency. Thus, iron sequestration inside host cells might play a role in leprosy by providing an optimal environment for the bacillus.

Type 2 lepra reaction as a cause of pyrexia of unknown origin.

Leprosy, a commonly encountered disease, can rarely present as a reactional state de novo with fever as the main presenting feature. Here we describe an uncommon presentation of leprosy [with type 2 lepra reaction] as pyrexia of unknown origin with prominent rheumatologic manifestations [acute polyarthritis], renal involvement and generalized lymphadenopathy with rare presentation of type 2 lepra reaction without the classic skin lesions of erythema nodosum leprosum, occurring in a treatment naive patient without prior history of leprosy.

Necrotic erythema nodosum reaction associated with histological alterations of Lucio's phenomenon.

Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.

Acute glomerulonephritis in a child with multidrug-resistant tuberculosis and multibacillary leprosy.

A 10-year-old boy from Papua New Guinea with multidrug-resistant tuberculosis and multibacillary leprosy developed acute glomerulonephritis while being treated as an inpatient at Thursday Island Hospital in the Torres Strait, Queensland. This is the first such case to be reported in Australia, where these diseases are uncommon and the combination is extremely rare, and it outlines important learning points regarding the aetiology of renal disease among patients with tuberculosis and leprosy.

Longitudinal ocular survey of 202 Filipino patients with multi-bacillary (MB) leprosy treated with 2 year WHO-multiple drug therapy.

The aim of this study was to describe the ocular conditions in multibacillary (MB) leprosy patients treated with 2 year WHO multiple drug therapy (MDT), consisting of dapsone, clofazimine and rifampin, a regimen expected to reduce ocular complications of leprosy. We conducted comprehensive eye examinations in 202 Filipino MB leprosy patients before, during, and after WHO 2 year MDT. Assessments were carried out for at least 5 years. Inflammatory "lepra" reactions occurred in 62% (reversal reaction, 52%; erythema nodosum leprosum, 10%); most were mild. Eye abnormalities consisted mostly of diminished corneal sensitivity before MDT (6%) and lagopthalmos (n = 7, 3.4%). Six of 7 lagopthalmos cases occurred in a subset of 132 patients with facial patches (5%). Visual acuity scores, intra-ocular pressures and pupil cycle times were unremarkable. Bacillary invasion, keratitis, episcleritis, iridocyclitis, ectropion, synechiae, glaucoma and cataract formation were not detected. Scleral clofazimine pigmentation was frequent, resolving in most within 3 years of treatment cessation. Facial patches at presentation may denote a higher risk for lagopthalmos. We propose the generally low rates of ocular problems reflected mild lepra reactions, due to anti-inflammatory properties of clofazimine, a relatively young cohort, and a readily accessible community-based clinic permitting earlier diagnosis and prompt treatment.

[Malignant transformation of plantar ulcers in leprosy: experience of National Leprosy Center in Casablanca]. / Dégénérescence carcinomateuse des maux perforants plantaires d'origine lépreuse: expérience du Centre national de léprologie de Casablanca.

Malignant degeneration is a late complication of plantar ulcers in leprosy. The objective of this study is to describe and analyze the epidemiological, clinical, and therapeutic aspects of this complication in Morocco. A retrospective study was conducted from January 2000 to December 2009 at the National Center of Leprosy (CNL) in Casablanca. All our patients had a histological confirmation. Ten patients were included in this study. There were seven men and three women, with a mean age of 58.8 years. Six patients had a multibacillary form of leprosy and four had a paucibacillary form. The average duration of the plantar ulcers was 34.4 years. Clinical appearance at diagnosis was an ulcerative and vegetative tumor. Treatment was by radical amputation. Evolution was marked by metastatic spread in six patients. One patient died of disseminated disease. In Morocco, leprosy has been on the decline since 1990, but the occurrence of late complications in the leprosy patient as carcinoma of plantar ulcers persists. Prevention of these complications should be part of the national fight against leprosy.

Renal involvement in leprosy: report of progression from diffuse proliferative to crescentic glomerulonephritis.

Renal involvement in leprosy has been reported rarely in the literature. Acute kidney injury in patients with leprosy is uncommon and may occur due to acute tubular necrosis, drug-induced interstitial nephritis and rarely crescentic glomerulonephritis. The latter with histologic confirmation of the diagnosis has been reported in very few cases of leprosy. A 25-year-old male, on therapy for multibacillary leprosy, was found to have deranged renal functions on evaluation for a history of nausea, vomiting, swelling and episode of haematuria. Kidney biopsy was performed twice over a period of 2 weeks, showing progression from diffuse proliferative glomerulonephritis to crescentic glomerulonephritis, pauci-immune in nature. The patient was treated aggressively with intravenous steroids, following which his renal functions stabilized. Crescentic glomerulonephritis, an extremely rare phenomenon in leprosy, should be considered in these patients presenting with features of acute kidney injury. Timely performed renal biopsy assists in accurate diagnosis and appropriate management of the patient, hence preserving renal parenchyma. Rapid progression from diffuse proliferative glomerulonephritis to crescentic glomerulonephritis in a patient with leprosy is described herein for the first time in the literature.

Ocular hypotension and hypotony in multibacillary leprosy patients; at diagnosis, during and after completion of multidrug therapy.

The prevalence and incidence of ocular hypotony (IOP < 7 mm Hg) and factors associated with them were determined in a Leprosy Referral Centre at Tamilnadu, India. Applanation intraocular pressures were measured every six months in a cohort of newly diagnosed multibacillary (MB) leprosy patients who were followed-up during the two year period of multidrug therapy (MDT) and for five years thereafter. Transient hypotony was present in two patients at the time of diagnosis, in 3 patients during MDT and in 9 patients after MDT with a cumulative prevalence of 4.65%. Transient ocular hypotension was present in 24 patients (8%) at disease diagnosis. 25 patients developed hypotension during MDT that was associated with trichiasis (HR 8.83 95% CI 2.06, 37.78 p = 0.003) and flare or/and cells (HR 4.60 95% CI 1.08, 19.64 p = 0.039). 29 patients developed ocular hypotension after MDT that was associated with punctate keratitis and uveal involvement. In general, MB leprosy patients with hypotension had a mean IOP of 12.60 mm Hg which differed significantly (p < 0.0001) from the mean IOP of 14.9 mm Hg in those who did not have hypotension. Transient hypotension and hypotony in MB leprosy patients are associated with signs of intraocular inflammation.