Leprosy reactions in postelimination stage: the Bangladesh experience.

BACKGROUND: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. OBJECTIVES: To describe the pattern and prevalence of leprosy reactions in the postelimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. RESULTS: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. CONCLUSION: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services.

Susceptibility of human iris stromal cells to herpes simplex virus 1 entry.

Ocular herpes simplex virus 1 (HSV-1) infection can lead to multiple complications, including iritis, an inflammation of the iris. Here, we use human iris stroma cells as a novel in vitro model to demonstrate HSV-1 entry and the inflammatory mediators that can damage the iris. The upregulated cytokines observed in this study provide a new understanding of the intrinsic immune mechanisms that can contribute to the onset of iritis.

Anti-Neutrophil Cytoplasmic Antibody-Associated Ocular Manifestations in Japan: A Review of 18 Patients.

ABSTARCTPurpose: To investigate ocular manifestations in patients positive for serum anti-neutrophil cytoplasmic antibodies (ANCAs) in Japan.Methods: The clinical records of patients who had ocular manifestations and who were serum ANCA positive between 2011-2017 at Tokyo Medical and Dental University Hospital were retrospectively reviewed.Results: Eighteen patients were identified to be positive for serum ANCA and had ocular manifestations, including optic nerve involvement (50%), scleritis (27.8%), iritis (27.8%), retinal vasculitis (16.7%), oculomotor disorder (16.7%), and peripheral ulcerative keratitis (11.1%). Six patients had ANCA-associated vasculitis (AAV), including 5 patients with granulomatosis with polyangiitis and 1 patient with microscopic polyangiitis. Most patients with optic nerve involvement were myeloperoxidase-ANCA positive. Contrastingly, most patients with anterior segment involvement were proteinase-3-ANCA positive.Conclusion: Ocular manifestations were observed in some patients positive for serum ANCAs. Serum ANCA evaluation is useful for identifying the etiology of ocular inflammation and for diagnosing AAV, a life-threatening disease.

Genetic modulation of antigen presentation by HLA-B27 molecules.

In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to present three different virus-derived epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct restricting HLA-B27 molecules on the cell surface. B cell lines were established from other members of the donor's family, including individuals suffering from ankylosing spondylitis and related diseases, and were tested for their ability to function as target cells in the same assay. None of the eight B cell lines that expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a family member that expressed HLA-B8 could present an epitope peptide restricted by that molecule. The B27 molecule in this family proved to be the B2702 subtype on isoelectric focusing gels, appearing in exactly the same position as B2702 from other cell lines that did present the peptide. To exclude mutations resulting in noncharged amino acid substitutions, cDNA coding for B2702 was cloned from the proband's cell line and sequenced. No coding changes were found. The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the B2702 molecules generated in this environment rendered these cells, after incubation with peptide, susceptible to lysis by peptide-specific CTL. These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by otherwise normal B2702 molecules in this family.

Early-onset pauciarticular juvenile rheumatoid arthritis associated with human leukocyte antigen-DRw5, iritis, and antinuclear antibody.

Evidence has been sought for a genetically determined predisposition among children with juvenile rheumatoid arthritis (JRA) who are also at particular risk for the development of inflammatory eye disease.45 unrelated Caucasian patients (41 female) with early-onset pauciarticular JRA were human leukocyte antigen (HLA) types. 28 of the study group were found to be HLA-DRw5 compared with 16 of 84 controls (X(2), 24.3, P = <0.001). 9 patients were HLA-DRw8 compared with 4 of 84 controls (X(2), 7.51, P = <0.01). Iritis developed in 24 of the 45 children studied, 17 of whom were typed as HLA-DRw5 when compared to controls (X(2), 26.76, P = <0.001) and 6 with iritis typed as HLA-DRw8 (X(2), 9.10, P = <0.01). Antinuclear antibody was found in the serum of 17 of the 28 patients typing as HLA-DRw5 compared with 4 of the 17 who did not have this antigen (X(2), 5.88, P = <0.02). No such association was seen in patients with HLA-DRw8. In a study of linked genes, a delta value of 0.090 was found for HLA-DRw5 with HLA-B12, of 0.070 for DRw5 with HLA-Cw4, and a value of 0.050 for DRw5 and HLA-Bw35. This suggests a linkage disequilibrium between HLA-DRw5 and these two B series alleles, a conclusion which was supported by haplotype analysis in families of 11 of the disease probands. HLA-DRw5 has not previously been reported to be increased in any rheumatic disease group. It is proposed that HLA-DRw5 is a genetic marker defining those at risk for early-onset pauciarticular JRA with iritis.

Experimental immunogenic rubeosis iridis.

We have developed a primate model of rubeosis iridis in monkeys systemically sensitized to crystalline beef insulin. After intravitreal insulin injection, the dose-related immunogenic inflammation includes cells, flare, fibrin, and blood in the anterior chamber. With more severe inflammation, posterior synechiae, iris bombé, and cataracts occur. Of particular importance, new blood vessels develop within the stroma and on the anterior surface of the iris. Following injection of small amounts of insulin, the anterior surface vessels may regress over time, and the iris regains its normal appearance and coloration. However, the new stromal vessels persist and are cuffed by inflammatory cells including plasma cells. After injection of large amounts of insulin, more extensive structural alterations develop as noted above in conjunction with persistent iris anterior surface and stromal neovascularization. The relationship of rubeosis iridis to clinical inflammatory syndromes and to previous laboratory studies is discussed. Stromal neovascularization was a consistent finding in this experimental model even when anterior surface vessels regressed. On the basis of these experimental data and a review of publications describing human pathology, we believe that a broadening of the classic definition of rubeosis iridis is waranted to include a recognition of the stromal component of the clinical and pathologic findings.

Chorioretinal scars in Fuchs' heterochromic iridocyclitis.

To determine the incidence of chorioretinal lesions in patients with Fuchs' heterochromic iridocyclitis, we reviewed the records of all patients with this disease seen at the Indiana University Uveitis Service, Indianapolis, since 1963. For comparison the records of age- and sex-matched patients with HLA-B27-positive iritis were also reviewed. The incidence of chorioretinal lesions in one or both eyes of patients with Fuchs' heterochromic iridocyclitis was significantly higher than in the patients with HLA-B27-positive iritis or than expected in the general population. Among the types of lesions manifested, the most notable increase was in toxoplasmosislike lesions. However, two of the five patients with these lesions had negative indirect hemagglutination assays for toxoplasmosis, down to undiluted serum. The reason for the high incidence of chorioretinal lesions in patients with Fuchs' heterochromic iridocyclitis is unclear and may be related to immunologic changes in these patients.

The functional significance of sacroiliitis and ankylosing spondylitis in Reiter's syndrome.

The frequent development of sacroiliitis and ankylosing spondylitis (AS) in patients suffering from Reiter's Syndrome (RS) has been stressed by a number of authors. This study was designed to ascertain the frequency of these problems in our RS patients, whether they were related to other clinical features of RS and what was the extent of the resulting disability. Fifty-five patients (50 men and 5 women) with RS with a mean duration of 9.3 years were assessed radiologically to determine the prevalence of sacroiliitis and thoracolumbar syndesmophyte formation. These radiological findings were correlated with HLA-B27, clinical features and functional status. Sacroiliitis was found in 22 patients (40%) but was mild in severity, frequently asymmetrical and very rarely associated with syndesmophyte formation. Sacroiliitis occurred significantly more commonly in patients with iritis and/or a prolonged disease duration (p less than 0.05) but although it was also found more frequently in HLA-B27 positive patients this was not significant (0.1 greater than p greater than 0.05). Some restriction in back movement was observed in 31 patients (56.3%) but only two patients satisfied New York criteria for AS and just one was functionally impaired by his back disease. Although the frequent finding of sacroiliitis in RS may provide an interesting insight into the interrelationship between RS and AS, our study shows that this sacroiliitis is commonly asymptomatic and does not provide a problem in management.

Similar chemotactic factor for monocytes predominates in different animal models of uveitis.

Anterior uveitis or iritis occurs in a variety of systemic diseases including sarcoid, Behcet's, and spondyloarthritis. Iritis is, therefore, presumed to result from a variety of pathogenetic mechanisms. We hypothesized that unique chemotactic factors should be associated with different etiologies for inflammation. We have tested this hypothesis using rabbit models of anterior uveitis. We have found that aqueous humor generally contained chemotactic activity for monocytes 24 h after an intravitreal injection of endotoxin, killed mycobacteria, or human serum albumin (in a rabbit previously immunized against human serum albumin). Anterior chamber paracentesis resulted in aqueous humor with a high protein content. However, in contrast to the other models of inflammation, paracentesis did not result in a cellular infiltrate in the anterior chamber, and aqueous humor after paracentesis was not chemotactic. For either immunologically mediated inflammation or for inflammation resulting from injection of a killed bacterial product, chemotactic activity could be digested by papain or trypsin and tended to coelute with albumin on either gel filtration or ion-exchange chromatography. These observations suggest that a similar chemotactic factor for monocytes appears to be associated with ocular inflammation that follows either an immune response or injection of a killed bacterial product.

Quantification of ocular inflammation: evaluation of polymorphonuclear leucocyte infiltration by measuring myeloperoxidase activity.

Myeloperoxidase (MPO) activity was measured in rabbit cornea and iris-ciliary body to quantitate the infiltration and accumulation of polymorphonuclear leucocytes (PMN's) following an inflammatory stimulus. Following injection of clove oil into the cornea, MPO activity could be detected in the cornea at 6 hr, reaching a maximum at 12 hr, and falling to non-detectable levels at 72 hr. MPO activity was only detected in the iris-ciliary body 24 hr after intracorneal clove oil injection. MPO activity in the iris-ciliary body increased in a dose-dependent manner following intravitreal injection of endotoxin. No MPO activity could be detected in cornea. Topical administration of dexamethasone inhibited MPO activity in cornea and iris-ciliary body 24 hr after intracorneal clove oil and intravitreal endotoxin injection, respectively. Measurement of MPO activity in ocular tissues could provide a useful tool to quantitatively evaluate the severity and time course of inflammation.