A relapse of pemphigus vulgaris in pemphigus herpetiformis or a phenotypic “switch”

Sir, Pemphigus herpetiformis (PH) was originally described by Jablonska et al. in 1975. Clinically, PH presents itself as a herpetiform dermatitis with immunopathological characteristics of pemphigus [1,2]. We report an exceptional case of typical pemphigus vulgaris (PV) relapsing after 36 years in PH. A 65-year-old patient, followed for PV for 36 years and treated with corticosteroid therapy with a remission for more than thirty years, consulted for pruriginous lesions evolving for the previous eight months. A dermatological examination revealed urticariform pruriginous ring lesions surmounted by small peripheral vesicles spread throughout the body (Fig. 1), sparing the mucous membranes, and without Nikolsky’s sign. After two non-specific skin biopsies, the histological examination revealed an intraepidermal bubble with acantholytic cells and eosinophilic spongiosis (Figs. 2a and 2b). Direct immunofluorescence confirmed the diagnosis of pemphigus and indirect immunofluorescence was at the upper limit. The diagnosis of a PV relapse in PH was retained and a dapsone-based treatment was initiated at a dose of 150 mg/day and stopped seven days later when met with hemolytic anemia. Oral corticosteroid therapy involving prednisone at a dose of 1 mg/kg/day was initiated but, given the persistence of the pruritus, the decision was to combine methotrexate at a dose of 12.5 mg/week. A good evolution and a decline within eight months were observed. An improved pruritus and the disappearance of the skin lesions were achieved after one month of treatment. PV and PH are two different anatomical and clinical entities of the autoimmune disease pemphigus, with distinct clinical, histopathological, and immunopathological characteristics [1,2]. Our observation documents a complete phenotypic “switch” of pemphigus with a transition from PV to PH both clinically, histologically, and immunologically. Several rare cases of PV switching to superficial pemphigus (SP) (“phenotypic switch”) have, since 1991, been reported, with a higher frequency this direction than otherwise; the transition period varies from six months to twenty years [3]. To the best of our knowledge, no case has been described of a progression from PV to PH. Having observed one firsthand, we are first to describe the case of a complete phenotypic switch from PV to PH. The mechanism of such a transition remains poorly understood and is often observed during a relapse. Some authors suggest that the effect of immunosuppressants on the desmoglein DSG3 more marked than on DSG1 could explain the relapse of PS in PH [3,4]. Future studies on the immunological factors and predictors of PV relapses after the discontinuation of treatment would be useful to better understand the mechanisms of a relapse in pemphigus, with or without a phenotypic transition.

Comparison of laboratory diagnostic methods for urogenital infections caused by Chlamydia trachomatis

According to the Russian-Swedish project there was performed a comparison of methods used for Chlamydia trachomatis detection in cervical samples, obtained from 397women and urethral samples from 253 men. All specimens were examined by direct immunofluorescence (DIF), polymerase chain reaction (PCR) and cell culture (CC). In high-prevalence group (group I) chlamydiae were detected in 17,8% and 28,0% of cases in men and women, respectively. Ingroup II containing patients who were subjected to screening examination, chlamydiae were found in 5% of cases both in men and women. PCR was shown to be the most sensitive when cervical samples in group I and cervical and urethral samples in group II were investigated. When urethral samples in group I were tested, DIF proved to have the highest sensitivity. All the methods used were found to be high specific. The search for standards of genital chlamydial infection diagnosis is in progress.

An Interesting Case of Nonlupus Full-House Nephropathy

Full-house immunofluorescence and endothelial tubuloreticular inclusions are known as characteristic features of lupus nephritis. However, both features are not pathognomonic for lupus nephritis. A kidney biopsy specimen showing full-house immunofluorescence pattern in the absence of autoantibodies and classical clinical features of Systemic Lupus Erythematosus (SLE) is now considered as nonlupus full-house nephropathy (FHN). Nonlupus FHN may be idiopathic or due to other disease processes known as secondary nonlupus FHN. Here, we report the case of a 36-year-old female who presented with nephrotic proteinuria with bland urine sediment. Additional analyses revealed normal serum antinuclear antibody (ANA), normal anti-double-stranded DNA (anti-dsDNA) antibodies, and normal serum C3 and C4 levels. A renal biopsy showed a normal-appearing glomerulus without any proliferation or capillary wall thickening and widespread glomerular immune deposits (full-house effect; IgA, IgG, IgM, C3, and C1Q) on direct immunofluorescence. Renal electron microscopy showed diffuse effacement of visceral epithelial cell foot processes and mesangial electron dense deposits. The patient was diagnosed as nonlupus FHN. There is a controversial role of steroids and other immunosuppressive drugs in the treatment of nonlupus FHN patients, but our case patient responded favourably to steroid therapy. The term nonlupus FHN can be used as an umbrella term for patients who do not satisfy the clinical and serological criteria of SLE.

Bullous Disease of Diabetes (Bullosis Diabeticorum)

Acanthosis nigricans, acrochordrons, diabetic dermatopathy, necrobiosis lipoidica, and bullous diabeticorum are some of the cutaneous symptoms of diabetes. Bullous illness (bullosis diabeticorum) is a blistering, non-inflammatory condition of the acral skin. Diabetes bullous illness is more common in people who have had diabetes for a long time or who have many comorbidities. Although the actual cause is uncertain, it is likely to be multifactorial. Neuropathy, nephropathy, vasculopathy, and UV (ultraviolet) light are all suggested to have a role. BD is most likely caused by the various problems that come with poorly managed diabetes. The exact number of people who have BD is unknown. The majority of case studies in the literature were based on a small number of cases. Bullous diabeticorum is a restrictive diagnosis, which necessitates a histological study that includes direct immunofluorescence to rule out other vesicobullous illnesses. In terms of BD management, no strong consensus has formed. The blisters have historically been thought to be self-limiting, with bullae resolving in 2 to 6 weeks if left untreated. In some cases antibiotic may be used. In this article we’ll be looking at Bullosis Diabeticorum. Its etiology, epidemiology, diagnosis, and treatment.

Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease that affects primarily patients older than 60 years. The majority of BP cases are spontaneous, but BP can also be triggered by certain drugs’ exposures. Since 2011, a growing number of observations has been reporting cases of BP in Type 2 diabetic patients. These forms have been linked to the use of a new category of anti-diabetic drugs called dipeptidyl peptidase inhibitors (DPP-4i) or gliptins, but to date, the exact pathophysiological mechanisms underlying this association are not completely elucidated. Although conventional and gliptin-associated BP are thought to share similar clinical and histopathological features, our thorough review of the most recent literature, shows that these 2 forms are quite distinct: DPP-4-i-associated BP seems to appear at an earlier age than spontaneous BP, it may manifest either as a noninflammatory or inflammatory phenotype, while the conventional form presents with a typical inflammatory phenotype. Additionally, an important distinctive histological feature was recently shown in Gliptin-associated BP: these forms may present a less significant eosinophils infiltrate in the upper dermis of peri-blister lesions compared to the skin of patients with spontaneous BP, and this seems a specific feature of the clinically non-inflammatory forms. In accordance with previous literature, we found that the direct immunofluorescence (DIF) gives identical findings in both DPP-4i-associated and conventional forms of BP which is an IgG and complement C3 deposition as a linear band at the dermal–epidermal junction in perilesional skin. Indirect immunofluorescence shows the presence of IgG circulating autoantibodies in the patient's serum which titer does not differ between spontaneous and DPP-4i-associated BP, while the specificity of these autoantibodies, may be different in spontaneous, induced non-inflammatory and induced inflammatory forms, epitope spreading phenomenon seems to play a role in determining these specificities. Further research, based on integrated epidemiological, clinical, histo-immunological and pharmacogenomic approaches, may give more insight into these forms of BP. This combined approach will allow to better define BP endotypes and to unveil the mechanism of spontaneous or drug-induced breakage of the immunotolerance to skin self-antigens.

The Second Study of Clinical and Immunological Findings in Anti-laminin 332-Type Mucous Membrane Pemphigoid Examined at Kurume University—Diagnosis Criteria Suggested by Summary of 133 Cases

BackgroundRecently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP.MethodsIn this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization.ResultsClinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMβ3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies.ConclusionsThis retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.

T-lymphocytes phenotypic composition of peripheral blood in patients with Graves’ disease undergoing conservative therapy with thiamazole

BACKGROUND: Effective control of autoimmune inflammation in Graves’ disease determines necessity to study the T helper (Th) and cytotoxic T-lymphocytes dysfunction, as well as the level of regulatory T-cells (Treg) activation in patients with Graves’ disease on thyrostatic medication, which will clarify the immunomodulatory effects of long-term thiamazole treatment serve as targets for more specific therapies.AIM: To study the phenotypic composition of T-lymphocytes in the peripheral blood of patients with Graves’ disease to assess the direction of immune response depending on thimazole-induced euthyroidism duration.MATERIALS AND METHODS: A single-center, cohort, continuous, open-label, controlled trial was conducted to assess the phenotypic composition of T-lymphocytes in peripheral blood in women with Graves’ disease on long-term thiamazole treatment. The phenotypic composition of T-lymphocytes was determined by flow cytometry using direct immunofluorescence with conjugated FITC monoclonal antibodies depending on the duration of thimazole-induced euthyroidism of long-term thiamazole treatment.RESULTS: The study included 135 women with Graves’ disease, mean age 43.09±12.81 years, 120 (88.91%) with a relapse of the disease and 15 (11.09%) with newly diagnosed hyperthyroidism. An increase of activated CD3+CD4+CD25+ was found in patients with Graves’ disease with a duration of thimazole-induced euthyroidism 5–8 months and 9–12 months, respectively, Me=0.94 (0.48–1.45), p=0.020) and Me=0.95 (0.41–1.80), p=0.025), in control group — Me=0.12 (0.03–0.68). Compared to the control an increase of CD4+CD25+CD127Low (Treg) was found in patients with a duration of thimazole-induced euthyroidism 5–8 and 9–12 months. The content of Treg in peripheral blood in Graves’ disease patients with a duration of thimazole-induced euthyroidism more than 12 months decreases, but remains elevated relative to the control.CONCLUSION: In patients with Graves’ disease with a duration of thimazole-induced euthyroidism 5–8 months and 9–12 months the level of Treg has been increased. The increase of activated Th (CD3+CD4+CD25+) persists independently of thimazole-induced euthyroidism. In patients with Graves’ disease with a duration of thimazole-induced euthyroidism for more than 12 months, there is a compensatory increase in regulatory T-lymphocyte, and the total number of T-helpers is restored to the control.

Experimental study on the expression and diagnostic significance of I-FABP in acute intestinal ischemia

Objective: To detect the expression and distribution of I-FABP in intestinal tissue and the changes of serum concentrations at different time of acute intestinal ischemia, and explore the significance and mechanism of I-FABP in early diagnosis of acute ischemic bowel disease. Methods: The selected 96 healthy adult SD rats were randomly divided into the experimental group and control group; 48 in each group. Each group was randomly subdivided into 6 groups with 8 rats in each group. The superior mesenteric artery was ligated in the experimental group and the peritoneal switch operation was performed in the control group. The venous blood samples were extracted from each group rats’ right ventricle at 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h after the operation and the concentration of I-FABP was tested respectively. Then the rats were killed, and the diseased intestinal tubes were cut out for paraffin sections. The I-FABP in intestinal tissue was stained by routine HE staining and direct immunofluorescence staining. Results: The I-FABP was mainly expressed in the epithelial villi of intestinal mucosa, and there was a small amount of expression in the intestinal submucosa and even the muscularis. Within 1 hour of intestinal ischemia, the number of I-FABP positive granules in the intestine and intestinal cavity increased gradually, and then gradually decreased after 1 hour. The difference has statistically significant between the experimental group and the control group (P < 0.05). The serum I-FABP: In the experimental group, the serum I-FABP concentration began to increase at 0.5 h, and reached a peak at 1 h (290. 24 ± 156.69) μg·L–1, then gradually decreased. Compared with the control group, the difference was statistically significant (P < 0.05). Conclusion: I-FABP usually mainly exists in the epithelial cells of intestinal mucosa. When acute intestinal ischemia occurs, the epithelial cells of intestinal mucosa permeability changes; I-FABP expression rapidly releases to intestinal tissue and intestinal cavity, and is absorbed into the blood. Therefore, I-FABP has certain clinical significance in early diagnosis and treatment of acute intestinal ischemia.