Direct immunofluorescence of skin biopsy: perspective of an immunopathologist.

BACKGROUND: By direct immunofluorescence (DIF), presence of immune complexes in the skin biopsy at various locations such as the dermo-epidermal junction, dermal blood vessels, etc. help to arrive at a diagnosis. AIMS: (1) To study the role of DIF in confirmation or exclusion of diseases involving skin vis-à-vis histopathology and clinical diagnosis, (2) to describe the annual spectrum of dermatologic conditions that present to a tertiary referral center and require DIF examination of skin biopsy for confirmation of diagnosis. METHODS: A total of 267 biopsies received over a period of 16 months in the Department of Immunopathology were analyzed along with clinical and histopathological details and the correlation between them was studied. RESULTS: DIF was positive in 204 skin biopsies. Of these, 127 biopsies showed good clinico-immuno-histopathological correlation. In 10 cases, only DIF could clinch the diagnosis. In another nine cases, immune deposits were noted, which were unexpected in light of clinical and histopathological diagnosis. The most common skin involvement was seen in vasculitides. DIF was, however, non-contributory in lesions like erythema multiformè, post Kala-azar dermal leishmaniasis, sarcoidosis, lupus vulgaris, pyoderma gangrenosum and prurigo nodularis. CONCLUSION: The DIF of skin in conjunction with histopathology gives the best diagnostic yield. It is invaluable in confirming the diagnosis of small vessel vasculitides and bullous lesions of skin and can be used as an additional tool to pinpoint the diagnosis of systemic and localized autoimmune diseases involving the skin.

Chronic macrocheilia: a clinico-pathological study of 28 patients.

Chronic macrocheilia has a multifactorial aetiology and is often a diagnostic and therapeutic challenge. Epidemiological information on this condition is scarce, most of the data reported relating only to granulomatous cheilitis. We have performed a detailed clinico-pathological analysis of all patients with chronic macrocheilia presenting to us during the last 6.5 years. Of the 28 patients identified, 13 (46.4%) had granulomatous cheilitis (GC), six (21.4%) had tuberculosis of the lip, three (10.7%) had leprous macrocheilia, two (7.1%) had multiple endocrine neoplasia type IIb, and one each had Ascher's syndrome and non-Hodgkin's lymphoma. Two patients were diagnosed as 'nonspecific cheilitis'. Histopathological differentiation between tuberculosis and GC was often not possible; but PCR for Mycobacterium tuberculosis was positive in all patients with tuberculosis and negative in four patients with GC in whom M. tuberculosis was sought. In spite of detailed clinical examination and investigations, a therapeutic trial was required to confirm the diagnosis in five (17.9%) patients. We have reviewed the available literature on this subject, and to our knowledge this study is the first of its kind. More such studies from other centres will help physicians to make an accurate aetiological diagnosis and treat this uncommon but disfiguring condition with confidence.

Combined 12-month WHO/MDT MB regimen and Mycobacterium w. vaccine in multibacillary leprosy: a follow-up of 136 patients.

A total of 136 patients with BI > or = 2 having been followed up for at least 2 years or more were included in the analyses. Seventy-seven out of 136 patients had completed three years follow up. All patients were given WHO/MDT MB regimen for 12 months and additionally 4 doses of Mycobacterium w. vaccine at 3-month intervals. The age of the patients varied from 6 to 77 years (mean 34 +/- 11.3 years) and they had the disease varying from 3 months to 7 years (mean = 1.9 +/- 1.4 years). The mean of the BI before starting treatment was 3.6 +/- 1.3. At the end of 2 years follow-up, a total of 54 patients out of the 136 (39.7%) had become smear-negative. A larger proportion of patients, 39/46 (84.8%) with BI of < or = 3 had become smear-negative, whereas, only 10/32 (31.3%) patients with BI between 3.1 to 4 and 5/58 (8.6%) highly bacillated patients having initial BI > 4 had become smear-negative at the end of 2 years. Out of the 77 patients who were available for follow up at 3 years, 30/33 (90.9%) patients with BI of < or = 3, 15/20 (75%) patients with BI between 3.1 to 4 and 13/24 (54.2%) patients having initial BI > 4, respectively, had attained smear negativity. Reactions occurred more frequently after 6 months of therapy and over a period of time their frequency gradually decreased, however, they continued to occur even two years after RFT. During the course of MDT and thereafter in follow up 4.6% and 1.3% of the patients developed new deformities or an increase in the existing grade of deformities, respectively. Three relapses (2 in LL and 1 in BL) occurred in patients having initial BI of > 4. One patient relapsed in the second year and the other two relapsed in the third year of follow up and were successfully treated with reintroduction of the same MDT MB regimen. Local ulceration healing with scar formation and regional lymphadenopathy were the only local reactions to the vaccine seen in 47/136 (34.5%) patients. All the patients showed histopathological improvement in the form of a gradual reduction of granuloma fraction. Although the results of this limited period follow up are satisfactory, a long-term follow-up in larger number of patients will settle the issue of safety and efficacy of shortened MDT MB regimen and the place of immunotherapy with M. w. vaccine in multibacillary patients.

Combined 12-month WHO/MDT MB regimen and Mycobacterium w. vaccine in multibacillary leprosy: a follow-up of 136 patients

A total of 136 patients with BI > or = 2 having been followed up for at least 2 years or more were included in the analyses. Seventy-seven out of 136 patients had completed three years follow up. All patients were given WHO/MDT MB regimen for 12 months and additionally 4 doses of Mycobacterium w. vaccine at 3-month intervals. The age of the patients varied from 6 to 77 years (mean 34 +/- 11.3 years) and they had the disease varying from 3 months to 7 years (mean = 1.9 +/- 1.4 years). The mean of the BI before starting treatment was 3.6 +/- 1.3. At the end of 2 years follow-up, a total of 54 patients out of the 136 (39.7%) had become smear-negative. A larger proportion of patients, 39/46 (84.8%) with BI of 4 had become smear-negative at the end of 2 years. Out of the 77 patients who were available for follow up at 3 years, 30/33 (90.9%) patients with BI of 4, respectively, had attained smear negativity. Reactions occurred more frequently after 6 months of therapy and over a period of time their frequency gradually decreased, however, they continued to occur even two years after RFT. During the course of MDT and thereafter in follow up 4.6% and 1.3% of the patients developed new deformities or an increase in the existing grade of deformities, respectively. Three relapses (2 in LL and 1 in BL) occurred in patients having initial BI of > 4. One patient relapsed in the second year and the other two relapsed in the third year of follow up and were successfully treated with reintroduction of the same MDT MB regimen. Local ulceration healing with scar formation and regional lymphadenopathy were the only local reactions to the vaccine seen in 47/136 (34.5%) patients. All the patients showed histopathological improvement in the form of a gradual reduction of granuloma fraction. Although the results of this limited period follow up are satisfactory, a long-term follow-up in larger number of patients will settle the issue of safety and efficacy of shortened MDT MB regimen and the place of immunotherapy with M. w. vaccine in multibacillary patients.

Impact of combined Mycobacterium w vaccine and 1 year of MDT on multibacillary leprosy patients.

A total of 20 bacteriologically positive multibacillary (MB) leprosy patients older than 18 years of age with a bacterial index (BI) of 2+ or greater were given standard World Health Organization multiple drug therapy (MDT-MB) for 12 consecutive months plus four intradermal doses of Mycobacterium w vaccine at 3 monthly intervals (Study group). Twenty age-matched MB patients were given WHO/MDT alone (Control group). The patients of both groups were followed up for 1 year. Improvements in the patients were periodically monitored by clinical (Ramu's score), bacteriological (SSS), histopathological (skin biopsy) and immunological (lepromin conversion) parameters. Study group patients showed more significant improvements in all parameters except for lepromin conversion compared to patients in the Control group. The incidence of type 1 reaction was more in the Study group (30% vs 10%), while the incidence of type 2 reaction was more in the Control group (25% vs 15%). Neuritis associated with reactions was seen more often in the Control group compared to the Study group (20% vs 10%). The addition of Mycobacterium w vaccine as an adjunct to the 1-year WHO/MDT regimen appears to be significantly more beneficial in MB leprosy patients with a high initial BI compared to WHO/MDT given alone. Studies on larger numbers of patients with extended follow up will be in order.

Concurrent skin and nerve histology in leprosy and its role in the classification of leprosy.

Concurrent skin and nerve histology was evaluated in 60 leprosy patients (25 BT, 28 BL and 7 LL). The twin aims were to study the comparative histology and the usefulness of nerve histology in the classification of the disease. In BT patients, clinical and histological classification was in agreement in 11 (44%) skin and 17 (68%) nerve biopsies. Concurrent skin and nerve histology was in consonance in 14 (56%) BT patients, while in 6 (24%) patients, only nerve histology was helpful in the classification of the disease, the skin histology being non-specific. Nerve histology was classified as BL in 3 (12%) BT patients, the skin histology was non-specific. In the BL group, the histology of 23 (82.4%) nerve biopsies correlated with the clinical classification, in contrast to skin histology which correlated with clinical assessment in 19 (68%) patients only. In the LL patients, the histology of nerve correlated with the clinical classification in 5 patients (71.4%), compared to histology of the skin in 4 (57%) patients only. The GF was higher in the nerves than in the skin throughout the leprosy spectrum (BT, BL, LL); the difference was, however, marginal in BL leprosy. The average bacteriological index (BI) was higher in nerves (4+) compared to that of skin histology and slit skin smears (3+) in BL leprosy. There was, however, no difference in the BI of the slit skin smears, skin and nerve biopsies in lepromatous leprosy.(ABSTRACT TRUNCATED AT 250 WORDS)

Tongue involvement in lepromatous leprosy.

BACKGROUND: Involvement of the oral cavity in lepromatous leprosy is well-documented. The tongue may demonstrate multiple nodules, thickening, and scarring. METHODS: Ten consecutive untreated patients with lepromatous leprosy with a bacteriologic index of 4+ or more were clinically and histopathologically studied for evidence of tongue involvement. RESULTS: Three patients showed clinical tongue involvement, as a nodulo-plaque lesion in one patient and fissured tongue (lingua plicata) in two patients. Tongue was clinically normal or showed nonspecific changes in the remaining seven patients. Histologic evidence of tongue involvement by lepromatous process was seen in six patients, including three without clinical involvement. CONCLUSIONS: We conclude from this study that the tongue is as prone to involvement by lepromatous process as buccal and palatal mucosa.

Maxillary antrum involvement in multibacillary leprosy: a radiologic, sinuscopic, and histologic assessment.

Thirty patients having lepromatous leprosy (22 males, 8 females) and showing radiological involvement of the maxillary antrum were subjected to sinuscopy, biopsy, and histopathological examination. Radiological observations showed diffuse opacity in 33.3% of the sinuses, localized mucosal thickening in 28.6%, and generalized thickened mucosa in 38.1%. Sinuscopy revealed inflamed mucosa as the most common finding (40%), followed by ulcerative (26.7%) and granulomatous (10%) lesions of the mucosal lining. The mucosal thickening (localized or generalized) evident on radiology was always associated with granuloma formation and acid-fast bacilli in the histology. The presence of an external nasal deformity indicated a statistically significant chance of encountering mucosal involvement on sinuscopy and histopathology (p < 0.05). There was more chance of finding positive sinuscopic lesions in those patients with a bacterial index above 3+.

Lichen Aureus.

A 23-year-old male presented with with-defined orange-brown patches on the lower legs of 6 months duration. The lesions were I and had been largely asymptomatic. The clinical picture and histopathology were consistent with lichen aureus.

Herpes Gestationis (pemphigoid Gestationis).

Three patients of herpes gestationis, a rare dermatosis of pregnancy, are being described along with a short review of literaure on the recent immunological backdrop. The characteristic periumbilical cutaneous lesions with classical buflae en cocade appeared during the third trimester of pregnancy and were controlled with corticosteroids. Classical histopathological basal cell necrosis in all the three patients and C3 deposition on dermo-epidermal interface in two patients were demonstrated. Post partum exacerbation was noted in all the three patients. Re occurred after 13 weeks in one patient, the rest did not report for follow up.

Eosinophilic Cellulms and Recurrent Granulomatous Dermatitis with Eosinophilia (wells Syndrome).

A 21 year old male developed 4 recurrences of Well syndrome with highly characteristic recurrent indurated urticarial plaque, circulatory eosinophilia, arthralgia, episodic asthma and histopathological flame fgwes. Direct immunofluorescence revealed periovascular deposits of C3 and IgM. A good response to corticosteroid was noticed.

Epidermolytic Hyperkeratosis with Mental Retardation, Breast Hypoplasia and Ventricular Septal Defect.

Two cases of epidermolytic hyperkeratosis are described, one having a generalised variety along with mental retardation, nystagmus, unilateral breast atrophy and intermittent divergent aquint, and the other having the localised variety associated with mental retardation, ventricular septal defect, sensorineural deafness, hypoplasia of first left metacarpal and extensive dental caries.