Cortisol and proinflammatory cytokine profiles in type 1 (reversal) reactions of leprosy.

PURPOSE: Cortisol levels in the circulation and at the sites of peripheral inflammation regulate type 1 (Reversal) reactions in leprosy akin to delayed type hypersensitivity reactions (DTH). In this study we determine the extent to which the differential mRNA expression of genes encoding cortisone-cortisol shuttle enzymes (11 ß hydroxysteriod dehydrogenase I & II (11 ß HSD I & II)), circulatory levels of proinflammatory cytokines (IL-6, IL-7, IP-10, IL-17F, IL-23, TNF-α, IL-1ß, PDGF BB and CRP) and cortisol are associated with development of type 1 reactions in leprosy. METHODS: Urine, blood and incisional skin biopsy samples from site of lesions were collected from 49 newly diagnosed untreated leprosy cases in T1R and 51 cases not in reaction (NR). mRNA expression levels of genes encoding 11 ß HSD I & II in skin biopsy samples were determined by realtime PCR. Cortisol levels from the lesional skin biopsies, serum and urine samples and serum proinflammatory cytokine levels were measured using ELISA. RESULTS: The mean expression ratios of 11 ß HSD I & II are significantly lower in leprosy cases with T1R when compared to the NR leprosy cases. Cortisol levels in lesional skin biopsies and in urine are significantly lower (p=0.001) in leprosy cases with T1R. Serum cytokine levels of IP-10, IL-17F, IL-IL-6 and TNF-α are significantly higher (p<0.05) in leprosy cases with T1R when compared the NR leprosy cases. CONCLUSION: Our study indicated an association of urinary and lesional skin cortisol levels with the manifestation of T1R in leprosy. IP-10, IL-17F, IL-6 and TNF-α can be potential prognostic serological markers and gene expression markers for early detection of type 1 reactions in leprosy.

Sensitive skin: an overview.

Sensitive skin is less tolerant to frequent and prolonged use of cosmetics and toiletries. It is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation. With the change in lifestyle and also with increased opportunity to use many new brands of cosmetics and toiletries, there has been an increase in females complaining of unique sensation in their facial skin. Sensitive skin presents as smarting, burning, stinging, itching, and/or tight sensation in their facial skin. The condition is found in more than 50% of women and 40% of men, creating a sizable demand for products designed to minimize skin sensitivity. Good numbers of invasive and non-invasive tests are designed to evaluate and predict the sensitive skin. Management includes guidelines for selecting suitable cosmetics and toiletries in sensitive skin individuals.

Type I hypersensitivity to Parthenium hysterophorus in patients with parthenium dermatitis.

BACKGROUND: Parthenium dermatitis is a major problem in urban and rural India. Patients with severe allergic rhinitis due to exposure to pollens of parthenium are reported to have parthenium specific IgE and IgG antibodies. Parthenium induces contact dermatitis by Type IV hypersensitivity and allergic rhinitis by Type-I hypersensitivity. AIMS: The study was undertaken to detect Type-I and Type-IV hypersensitivity amongst patients with parthenium dermatitis. METHODS: Fourteen patients with clinical features of parthenium dermatitis who patch tested positive to parthenium were included in the study. Patch testing was done by standard method and results interpreted as recommended by the ICDRG. Serum IgE was determined by chemiluminescence immuno assay system (CLIA). Prick testing was performed and interpreted by standard method. RESULTS: Twelve out of the 14 patients included, showed a positive prick test. Serum IgE was elevated in all patients to varying degrees (mean IgE-1279.9 IU/ml; N--up to 100 IU/ml). CONCLUSION: The positive patch test, prick test and elevated serum IgE suggest that both Type-I and Type-IV hypersensitivity may play a role in the induction and perpetuation of parthenium dermatitis in most patients. To date, delayed hypersensitivity was thought to be solely responsible for parthenium dermatitis. This study suggests that a combined type-I and type IV hypersensitivity mechanisms may be operational.

Study of histamine wheal suppression by dexamethasone with and without iontophoresis.

BACKGROUND: Iontophoresis increases the penetration of drugs into the skin by electric current. The ability of topical steroids to reduce the size of the histamine wheal was used to assess the efficacy of topical dexamethasone delivered with and without iontophoresis. AIM: To determine the wheal suppressing ability of dexamethasone delivered with and without iontophoresis. METHODS: A template with three squares of 3x3 cm was placed on both forearms of 20 volunteers and the edges marked. A gauze piece soaked in 2 ml of dexamethasone solution was placed on the flexor aspect of the left forearm and the electrode, an aluminum foil was placed on it and connected to the negative pole (since dexamethasone is negatively charged). An electric current was passed for 15 minutes. Similarly, on the right forearm, a dexamethasone soaked gauze piece was placed without iontophoresis. Histamine wheal suppression was assessed at the end of 30 min, 1 hr and 2 hrs, on both sides. Statistical analysis was done using an independent t-test. RESULTS: There was a statistically significant difference in wheal suppression at 30 min (p=0.006) on the left hand where iontophoresis was used. CONCLUSION: Our experiment showed that topical dexamethasone with iontophoresis has the maximum effect at the end of 30 minutes and is more effective than dexamethasone without iontophoresis.

Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance.

BACKGROUND: Desensitization with drugs may be indicated in some clinical situations. Apart from large experiences with beta-lactam antibiotics and cotrimoxazole in HIV infection, experience with other drugs is limited. Rifampicin may elicit exanthema and urticaria, and their pathomechanisms are not known in detail. Since therapy with rifampicin may be indispensable in mycobacterial infections or against multiresistant Staphylococcus aureus, desensitization may be indicated in some patients. OBJECTIVE: Report of immediate hypersensitivity to rifampicin and description of diagnostic and desensitization procedures. METHODS: We report 3 patients with immediate urticarial reactions to rifampicin. Diagnostic procedures included skin and in vitro tests (specific IgE, lymphocyte transformation test, LTT, and CAST). The non-irritant cutoff concentration was evaluated in 24 volunteers. A 7-day desensitization procedure was used. RESULTS: Only intradermal tests at a dilution of at least 1:10,000 (concentration of rifampicin approximately 0.006 mg/ml) were true positive, whereas in vitro tests (IgE, LTT and CAST) did not correctly identify hypersensitive patients. Two patients had positive accidental reexposure. All patients were successfully desensitized with rifampicin according to a slow 7-day protocol. CONCLUSIONS: Rifampicin rarely elicits immediate hypersensitivity symptoms which may be diagnosed by intradermal skin tests. In vitro tests did not contribute to the diagnosis. Therefore, an IgE-mediated mechanism remains to be proven. Desensitization with rifampicin using different protocols has been reported. In our 3 cases, clinical tolerance to rifampicin was achieved using a 7-day protocol.

Antigenic trigger for type 1 reaction in leprosy.

Type 1 (reversal or upgrading) reactions occur during or after chemotherapy in around 10% leprosy patients [Int J Lepr Other Mycobact Dis 61 (1993) 8-15]. The cause of this immunological upgrading is incompletely defined, although the approximately 2-fold increased risk of reaction in patients vaccinated with Mycobacterium w suggests that infection by mycobacteria other than Mycobacterium leprae may trigger this phenomenon [Vaccine 13 (1995) 1102-1110]. We report a case of borderline lepromatous leprosy in which we studied the antigenic specificity of peripheral blood mononuclear cells immediately before, and then during, a Type 1 reaction which provides more direct evidence in favor of this hypothesis.

Keratitis.

Corneal inflammation or keratitis is a significant cause of ocular morbidity around the world. Fortunately, the majority of the cases are successfully managed with medical therapy, but the failure of therapy does occur, leading to devastating consequences of either losing the vision or the eye. This review attempts to provide current information on most, though not all, aspects of keratitis. Corneal inflammation may be ulcerative or nonulcerative and may arise because of infectious or noninfectious causes. The nonulcerative corneal inflammation may be confined to the epithelial layer or to the stroma of the cornea or may affect both. For clarity, this section has been divided into nonulcerative superficial keratitis and nonulcerative stromal keratitis. While the former usually includes hypersensitivity responses to microbial toxins and unknown agents, the latter can be either infectious or noninfectious. In the pathogenesis of ulcerative keratitis, microorganisms such as bacteria, fungi, parasites (Acanthamoeba), or viruses play an important role. Approximately, 12.2% of all corneal transplantations are done for active infectious keratitis. Available world literature pertaining to the incidence of microbial keratitis has been provided special place in this review. On the other hand, noninfectious ulcerative keratitis can be related to a variety of systemic or local causes, predominantly of autoimmune origin.

Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases.

We identified functionally polarized subsets of CD4 memory T cells on the basis of the expression of CD11a, CD45RA and CD62L. Within the several phenotypically distinct subsets of CD4 memory cells are two that, upon stimulation, produce primarily IL-4 (MT(2), CD45RA(-)CD62L(+)CD11a(dim)) or primarily IFN-gamma (MT(1), CD45RA(-)CD62L(-)CD11a(bright)). In addition, four other phenotypically distinct subsets of CD4 cells have unique cytokine profiles. To determine the clinical relevance of the representation of these cell types, we analyzed blood from patients with the chronic diseases leprosy and atopy. These diseases are characterized as immunologically polarized, since T cell responses in affected individuals are often strongly biased towards T(h)1 (dominated by IFN-gamma production) or T(h)2 (IL-4 production). We show here that this polarization reflects homeostatic or differentiation mechanisms affecting the representation of the functionally distinct subsets of memory CD4 T cells, MT(1) and MT(2). Significantly, the representation of the MT(1) and MT(2) subsets differs dramatically between subjects with tuberculoid leprosy (a T(h)1 disease), or lepromatous leprosy or atopic disease (T(h)2 diseases). However, there was no difference in the cytokine profiles of these or any of the other finely resolved CD4 subsets, when compared between individuals across all disease states. Thus, it is the representation of these subsets in peripheral blood that is diagnostic of the polarized state of the immune system.

Zinc-controlled Th1/Th2 switch significantly determines development of diseases.

Functional, excessive-possibly temporary-deficiencies of the trace element zinc can change immune functions prematurely from predominantly cellular Th1 responses to humoral Th2 responses. T helper (Th1) cells produce cytokines such as interleukin-2 (IL-2) and interferon gamma, thereby controlling viral infections and other intracellular pathogens more effectively than Th2 responses through cytokines such as IL-4, IL-5, IL-6 and IL-10. The accelerated shift from the production of extra Th1 cells during these cellular immune activities to more Th2 cells with their predominantly humoral immune functions, caused by such a zinc deficiency, adversely influences the course of diseases such as leprosy, schistosomiasis, leishmaniasis and AIDS, and can result in allergies. It is noteworthy that AIDS viruses (HIVs) do not replicate in Th1 cells, which probably contain more zinc, but preferentially in the Th0 and Th2 cells; all the more so, because zinc and copper ions are known to inhibit intracellular HIV replication. Considering the above Th1/Th2 switch, real prospects seem to be offered of vaccination against such parasites as Leishmania and against HIVs.

Atopy and IgE in patients with leprosy.

The atopic status of patients with leprosy was assessed by medical history, physical examination, serum total IgE, and specific IgE antibodies to common allergens (by skin testing and RAST). Tests for specific IgE antibody to Mycobacterium leprae were performed by RAST and immunoblotting technique. We studied 28 patients with leprosy and 49 control subjects. The two groups did not differ significantly in the prevalence of atopic disease. The IgE level was significantly higher in the patients, however, than in the control subjects, whether there was atopy (296.1 versus 96.3 IU/ml) or not atopy (72.9 versus 18.9 IU/ml). Neither RAST nor immunoblotting technique detected significant levels of IgE antibodies to M. leprae. Our data indicate that leprosy was associated with increased total IgE level, but clinical atopy in patients with leprosy was similar to that in control subjects. The observed IgE increase in patients with leprosy appears to be generally nonspecific.

Evaluation of standard Dharmendra lepromin.

Dharmendra lepromin standardized at Central JALMA Institute for Leprosy (CJIL) by bacterial counts was used by different observers in four different Centres to assess the early and late reactions. Patients taken into the study were from different ethnic groups in different regions of the country. Comparable skin reactions were found at the Bombay Leprosy Project (BLP), Bombay and at the CJIL, Agra wherein a large number of patients were taken in the study. Similarly, when a smaller number of patients were taken in the study at the Base Hospital (BH), Barrackpore, and at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, the skin reactions noted in patients at these Centres were again found to be statistically comparable.