Evaluation of key histologic variables in skin biopsies of patients of borderline leprosy with type 1 lepra reaction.

BACKGROUND: Leprosy remains an important health problem mainly in the African and South-East Asia regions. Type 1 reaction is an immune-mediated phenomenon known to complicate at least 30% of patients of leprosy. Diagnosing type 1 reaction correctly is important for timely institution of therapy to prevent and treat neuropathy-associated disability and morbidity. There is paucity of literature on definitive criteria for histologic diagnosis of type 1 reaction. This study was conducted to determine the key histologic variables for diagnosing type 1 reaction. METHODS: This was a prospective study recruiting 104 patients with borderline leprosy. Three pathologists blinded to the clinical diagnosis independently assessed the cases. The agreement between each histological variable and clinical diagnosis was then calculated by using Cohen's kappa (Κ) coefficient. RESULTS: Histological diagnosis of type 1 reaction was given to 27 (67.5%) of 40 clinically diagnosed cases of type 1 reaction cases. Histological variables chosen as key variables for histological diagnosis of type 1 reaction were presence of giant cells, dermal edema, intragranuloma edema, granuloma fraction 31-50%, and presence of medium to large giant cells. CONCLUSION: This study has shown that T1R are still underdiagnosed histologically in comparison with clinical assessments. The key variables for diagnosing type 1 reaction were proposed.

Atypical cutaneous features in adult onset Still's disease.

Adult onset Still's disease is a rare but potentially serious disease. We present five cases of adult-onset Still's disease seen by us over a period of one year. The patients were all females and 28-39 years of age. Symptoms had been present for 2-6 weeks in three patients. The other two had been on a few years' follow-up for rheumatoid arthritis before the onset of rashes and fever. The patients had persistent erythematous maculopapular eruptions on face, body and extremities, with moderate to severe pruritus and/or a burning sensation that decreased their quality of life. The typical evanescent rash was not observed. High ferritin values were detected in all the patients and total serum IgE was increased in two. All the patients were started on oral prednisolone (0.5-1.0 mg/kg/day), and methotrexate (10-15 mg/week) had to be added in three patients. One patient was started on tocilizumab due to recalcitrant disease and one was lost to follow-up. Further investigation and classification of the various atypical cutaneous findings in adult-onset Still's disease is necessary.

Otophyma: a rare benign clinical entity mimicking leprosy.

Otophyma is a rare condition characterized by edematous deformation of the ear that is considered to be the end-stage of an inflammatory process such as rosacea and eczema. This report illustrates a case in an elderly male, originally thought to have leprosy. Biopsy revealed a nodular infiltration of inflammatory cells around adnexal structures and an intraepidermal cyst. No acid-fast organisms were identified. We present a patient who is of a different ethnic group than usually seen with this disease and provide a review of the clinical presentation, histopathological features, and management of this rare condition.

A randomized clinical trial comparing immediate active motion with immobilization after tendon transfer for claw deformity.

PURPOSE: Immobilization after tendon transfers has been the conventional postoperative management. A recent study indicated beneficial effects of an immediate active motion protocol (IAMP) after tendon transfer for claw deformity correction compared with effects in a historical cohort. In this study, we further tested this hypothesis in a randomized clinical trial comparing the effectiveness of the IAMP with that of conventional immobilization. METHODS: Fifty supple claw hand deformities were randomized postoperatively into 2 equal groups for IAMP and immobilization. Therapy began on the second postoperative day for the IAMP group and on the twenty-second postoperative day for the immobilization group. The primary outcome measures were deformity correction, active range of motion of digits, tendon transfer insertion pullout, and time until discharge from rehabilitation. Secondary outcome measures were swelling, pain, hand strength, and dexterity. Both groups were compared at discharge from rehabilitation and at the last clinical follow-up (at least 1 year postoperatively). RESULTS: Assessments were available for all 50 patients at discharge and for 23 patients in each group at follow-up. The average follow-up was 18 months for the IAMP group and 17 months for the immobilization group. Deformity correction, range of motion, swelling, dexterity, and hand strength were similar for both groups at discharge and a follow-up. There was no evidence of tendon insertion pullout in any patient of either group. Relief of pain was achieved significantly earlier with IAMP. Morbidity was reduced by, on average, 22 days with IAMP. CONCLUSIONS: We found that the immediate active motion protocol is safe and has similar outcomes compared with those of immobilization, with the added advantage of earlier pain relief and quicker restoration of hand function. Immediate motion after tendon transfer can significantly reduce morbidity and speed up the rehabilitation of paralytic limbs, and it may save expense for the patients.

Deciphering spongiotic dermatitides.

Clinicians often receive pathology reports proclaiming a spongiotic dermatitis with little in the form of a cogent differential diagnosis. In some cases, this is a natural consequence of the nonspecific nature of the reaction pattern due to matters of sampling error and/or lesional evolution. Further, some conditions are so synonymous in their histologic presentation that to choose one without mention of the other, purely on a histologic basis, may serve to inadvertently mislead the clinician. Despite the often significant histologic overlap amongst the varying spongiotic dermatitides, there are many subtle, yet detectable, features that may serve as clues to the pathogenetic process. Identification and subsequent communication of these features help to narrow the diagnostic possibilities with the ultimate goal of contributing to effective patient management. This article focuses on the histologic details of the spongiotic reaction pattern and presents some of the more common variations of its manifestation which, in conjunction with ancillary inflammatory elements, may help the histomorphologist to arrive at a more concise list of diagnostic possibilities.

The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis.

BACKGROUND: Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity. METHODS: In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared. RESULTS: Reactions were under-diagnosed, with 32-62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34-53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves. CONCLUSIONS: This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.

Remitting seronegative symmetrical synovitis with pitting edema in leprosy.

A 67-year-old man, who had widespread and well-defined erythematous violaceous hyperkeratotic plaques on his skin, was diagnosed with borderline tuberculoid leprosy. The patient began treatment with clofazimine, rifampicin, and dapsone, but 15 days afterwards he complained of acral edema with godet sign. Magnetic resonance imaging was done, and the case was interpreted as remitting seronegative symmetrical synovitis with pitting edema. About 8 mg/day of methylprednisolone were started with excellent response.

Mycobacterium ulcerans infection (Buruli ulcer): a case report of the disseminated nonulcerative form.

The World Health Organization recognizes Mycobacterium ulcerans infection (Buruli ulcer) as a reemerging disease. Classically, lesions are indolent, undermined ulcers of the skin. The characteristic histopathologic changes are provoked by a soluble toxin of M ulcerans that is necrotizing and immunosuppressive. After tuberculosis and leprosy, Buruli ulcer is the third most common mycobacterial disease in humans. We report Buruli ulcer in a patient in Benin, West Africa, with widespread edema and diffuse induration of approximately one half of the skin of the trunk. There was no ulceration. The tissue studied was a 16-cm portion excised from the center of the large surgical specimen. Histopathologic analysis showed massive contiguous necrosis of the dermis and subcutis in sections of biopsy specimens from the center, at 2-cm intervals in two radii from the center to the periphery, and at 5-cm intervals around the margin. Acid-fast bacilli infiltrated all specimens except at one peripheral site. Samples of the entire surgical specimen taken from seven sites before fixation were polymerase chain reaction and culture positive for M ulcerans. The disseminated nonulcerative form of M ulcerans infection is well known, but is now increasingly frequent in some highly endemic areas, especially in West Africa. This patient died within 48 hours postsurgery, but cause of death was not established. The only regularly effective treatment for advanced lesions is surgical excision of all infected tissue. Estimation of the lateral limits of invasion by M ulcerans may help the surgeon establish the optimal extent of excision. Refinement of the basic concept we used and adaptation to preoperative assessment of the limit of bacterial invasion are urgently needed, especially for massive lesions.

Multiple synovial swellings in BT leprosy. A case report.

A case of Leprosy with multiple synovial swellings has been reported. Rarely these swellings may be an initial presentation and at sites other than dorsum of hand or ankle as was in this case. The literature on the subject is briefly reviewed.

Sequential histological study of lepromin reaction.

Skin testing with Dharmendra antigen was performed on 55 patients with TT, BT, BL, and LL types of leprosy and the reaction measured at different intervals from 24 hr to 28 days. At various time intervals, a biopsy specimen was taken from the reaction site. In TT and BT cases, the erythema was maximum at 48 hr; while the induration was maximum at 21 days. The sequence of the histological changes was built up on the observations made from different cases at varying intervals. The quantum of cellular exudate was high in TT and BT cases as compared to BL and LL cases. The cellular distribution showed loose scattering of cells in the LL and BL types and attempts to form tight clusters in the TT and BT cases. Neutrophils were predominant during the first 48 hr, particularly in the LL, BL, and BT types. By 72 hr the cells were mainly lymphocytic. A tendency for the lymphocytes to cluster around nerve twigs was seen in the TT and BT cases. In the early reaction the quantum of exudate correlated both with erythema and induration; while in the late reaction, it correlated with induration only. The intensity of the early lepromin reaction was more in BT than in TT leprosy, while the induration in the late reaction was more in TT than in BT types. The significance of these findings is discussed.