Direct Immunofluorescence Findings Research Articles

Ocular Mucous Membrane Pemphigoid: The Effect of Risk Factors at Presentation on Treatment Outcomes

PurposeAnalyze the influence of risk factors at presentation in the long-term immunosuppressive therapy (IMT) outcomes of ocular mucous membrane pemphigoid (OMMP). DesignRetrospective multicenter study. ParticipantsOMMP patients seen at Duke Eye Center, Tecnologico de Monterrey, and Hospital Clinic of Barcelona from 1990–2022. MethodsData at presentation on demographics, direct immunofluorescence and ocular findings, extraocular sites of involvement (EOM) and prior treatments, in patients with a clinical and/or laboratory diagnosis of OMMP, were analyzed with multivariable analysis and Kaplan-Meier plots to identify factors associated with adverse outcomes. Main outcome measures(1) inflammatory control (no conjunctival inflammation in both eyes at three months on IMT); (2) relapse (new-onset inflammation after absolute control in either eye); (3) progression (≥1 cicatrizing stage progression in either eye); and (4) vision loss (>2 Snellen lines). Results117 patients (234 eyes), 61% (71/117) women, with a mean age of 66.6 (standard deviation (SD) 12.4, range: 37–97) years and a median follow-up of 34 (interquartile range Q1 16, Q3 66; range: 3–265) months. Inflammatory control was achieved in 57% (67/117) patients, with high-risk EOM (HR-EOM), including esophageal, nasopharyngeal, and/or genital [adjusted odds ratio (aOR) 12.51; 95% confidence interval (CI), 2.61–59.99; P=0.002] and corneal scarring (aOR 3.06; 95% CI, 1.15–8.14; P=0.025) as significant risk factors for persistent inflammation. Disease relapse, progression, and vision loss occurred in 20% (23/117), 12% (14/117), and 27% (32/117) of patients, respectively. Baseline corneal scarring was a risk factor for relapse [adjusted hazard ratio 4.14; 95% CI, 1.61–10.62; P=0.003], progression (aOR 11.46; 95% CI, 1.78–73.75; P=0.010), and vision loss (aOR 3.51; 95% CI, 1.35–9.10, P=0.010). HR-EOM was associated with stage progression (aOR 34.57; 95% CI, 6.57–181.89; P<0.001) and vision loss (aOR 8.42; 95% CI, 2.50–28.42, P=0.001). There were no significant differences between IMT regimes and relapse (P=0.169). ConclusionsOMMP presenting with HR-EOMs and corneal scarring has an increased risk of stage progression and vision loss. Corneal scarring and severe inflammation at baseline were associated with an increased risk of relapse. A disease progression staging system incorporating both the HR-EOMs and corneal involvement is required to predict the visual outcome of OMMP better.

Concordance of clinical, histopathologic and direct Immunofluorescence findings in patients with intraepidermal immunobullous disorders.

To determine the concordance among clinical, histopathological and immunofluorescence as diagnostic methods for intraepidermal immunobullous disorders. The prospective cross-sectional study was conducted at the Institute of Skin Diseases, Karachi, from December 2020 to December 2022, and comprised adult patients of either gender presenting with complaints of bullae, vesicles, pustules and crusts on the skin or mucous membrane. Diagnostic findings of each patient as obtained by clinical assessment, microscopy and direct immunofluorescence were compared. Data was analysed using SPSS 19. Of the 81 patients, 41(50.6%) were males and 40(49.4%) were females. The overall median age was 35 years (interquartile range: 23 years), with 66(75%) patients aged 19-55 years. The predominant body site involved was the trunk 49(60.5%), followed by mucosa 26(32.1%). Clinical diagnosis detected 80(98.7%) cases, compared to 76(93.8%) by microscopy and 81(100%) by direct immunofluorescence. Direct immunofluorescence was found to be the gold standard for a confirmatory diagnosis of intraepidermal immunobullous disorders, especially when clinical and histopathology findings were inconclusive.

Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid.

The aim of this study was to describe the direct immunofluorescence (DIF) findings and factors affecting conjunctival biopsy positivity in patients clinically diagnosed with ocular mucous membrane pemphigoid (OMMP). This retrospective observational case series included patients with clinical OMMP who underwent conjunctival biopsy for DIF in at least 1 eye between 2018 and 2021 in an institutional setting. The primary outcome measures were association of age and chronic ocular complications with biopsy positivity. Of 61 patients, DIF positivity was seen in 33 (54.1%) clinically suspected cases of OMMP. Of 39 patients who underwent bilateral biopsy, 23 (59%) were positive, of which 12 (52%) were positive in both eyes while 11 (48%) were positive in 1 eye. Of 22 patients who underwent unilateral biopsy, 10 (45%) were positive. Of the 100 biopsied eyes, 45 (45%) were DIF positive. Among the immunoreactants studied, linear deposition of C3 was seen in all 45 positive eyes (100%). Increasing age was significantly associated with higher likelihood of biopsy negativity ( P = 0.032), whereas a greater Sotozono chronic ocular complication score, indicative of disease severity, was associated with low likelihood of biopsy positivity ( P = 0.0042) and lower overall expression of immunoreactants on DIF ( P = 0.0007). Older patients and patients with more severe ocular surface disease sequelae are likely to have negative DIF results. To optimize the chances of confirming the diagnosis of OMMP by DIF, both eyes should be biopsied early in the disease course. If 1 eye is being biopsied, the less affected eye must be chosen.

Local neutrophil and eosinophil extracellular traps formation in pyodermatitis pyostomatitis vegetans.

Pyodermatitis pyostomatitis vegetans is a rare inflammatory condition, affecting the skin and/or mucous membrane. Some cases include both skin and mucous involvement, whereas others develop either skin or mucous lesions only. The typically affected areas are the scalp, face, trunk and extremities, including the flexural areas and umbilicus. Clinical features show erosive granulomatous plaques, keratotic plaques with overlying crusts and pustular lesions. Among mucous lesions, oral mucosa is most frequently involved, and gingival erythema, shallow erosions, cobblestone-like papules on the buccal mucosa or upper hard palate of the oral cavity are also observed. Some of the lesions assume a 'snail track' appearance. Although there are several similarities between pyodermatitis pyostomatitis vegetans and other diseases, that is pyoderma gangrenosum, pemphigus vegetans and pemphigoid vegetans, the histopathological features of pyodermatitis pyostomatitis vegetans are unique in that epidermal hyperplasia, focal acantholysis and dense inflammatory infiltrates with intraepidermal and subepidermal eosinophilic microabscesses are observed. Direct immunofluorescence findings are principally negative. Activated neutrophils are supposed to play an important role in the pathogenesis of pyodermatitis pyostomatitis vegetans. The expression of IL-36 and neutrophil extracellular traps (NETs) was observed in the lesional skin, and additionally, eosinophil extracellular traps (EETs) was detected in pyodermatitis pyostomatitis vegetans. A possible pathogenic role of NETs and EETs in the innate immunity and autoinflammatory aspects of pyodermatitis pyostomatitis vegetans was discussed.

A retrospective study on the direct immunofluorescence findings in pigmented purpuric dermatosis.

Pigmented purpuric dermatosis (PPD) is characterized by grouped petechiae, purpuric macules, and pigmentation in the bilateral lower extremities. It runs a chronic and relapsing course. Pathophysiology is poorly understood, but it has been proposed to be an immune-complex disease or capillaritis. This study aimed to determine the incidence and patterns of positive direct immunofluorescence (DIF) findings in patients with clinically and histopathologically confirmed PPD. The association between DIF deposition type and clinical profile was also analyzed. Patients with a clinical and histopathologic PPD diagnosis who had undergone DIF studies at a tertiary medical center with attached dermatopathology and immunofluorescence diagnostic centers between January 2002 and December 2021 were included in this study. Data on age, sex, disease duration, comorbidities, and drug intake were collected from medical records. There were 65 patients who satisfied the inclusion criteria. Among them, 58 (89%) had at least one positive finding and 53 (82%) were vascular deposition of immunoglobulin (Ig), complement, or fibrinogen. The most common vascular deposition was fibrinogen (71%) followed by C3 (62%), IgM (18%), IgA (6%), and IgG (3%). Fibrinogen deposition was associated with hypertension (p < 0.03). There was no association between vascular DIF deposition of IgG, IgA, and C3, with age, sex, comorbidities, disease duration, and drug history. The most common DIF findings in PPD were vascular deposition of fibrinogen and C3, with or without Ig presence. DIF findings supported a vascular origin in PPD but not an immune complex-mediated disease. Hypertension was associated with fibrinogen deposition and may play a role in its pathophysiology.

Accuracy of serration pattern analysis by direct immunofluorescence in subepidermal autoimmune blistering diseases.

Background Direct immunofluorescence (DIF) is essential for the diagnosis of sub-epidermal immunobullous diseases (SIBD). Bullous pemphigoid (BP), a sub-epidermal immunobullous disease, shows linear IgG and C3 deposition along the dermo-epidermal junction by DIF. However, similar histological and DIF findings are also seen in epidermolysis bullosa acquisita (EBA). High-power examination of antibody deposition by DIF in a "u" or "n" serrated pattern can help differentiate these two entities. Aims/Objectives The aim of this study was to determine the diagnostic accuracy of serration patterns in IgG-mediated sub-epidermal immunobullous disease. Methods All cases of IgG-mediated sub-epidermal immunobullous disease diagnosed over the past 2 years and 9 months period and confirmed serologically, were included. Examination of the serration pattern in DIF was assessed on oil emersion. Salt split skin indirect immunofluorescence (SSS IIF), BP180 enzyme-linked immunosorbent assay (ELISA), profile ELISA and BIOCHIP mosaic were performed, wherever available. Results This study included 74 cases of bullous pemphigoid, eight cases of mucus membrane pemphigoid (MMP) and one case of epidermolysis bullosa acquisita. The characteristic zigzag "n" pattern was visualised in 66 out of 82 cases (80.5%) of the pemphigoid group (BP + MMP); the single epidermolysis bullosa acquisita case showed the "u" serrated pattern. No statistical correlation was seen between serration pattern and BP180 positivity by ELISA (P = 0.05). Limitations The study is limited by the single case of epidermolysis bullosa acquisita (which could be due to rarity of this disease in north Indian population due to genetic variation), lack of detailed serological investigations and immunoblot in all cases. Conclusion Serration pattern analysis is an easy-to-interpret and highly useful technique for characterisation of sub-epidermal immunobullous diseases.

P19 Diagnostic conundrums in paraneoplastic pemphigus

Abstract Paraneoplastic pemphigus (PNP) is a subset of pemphigus, a group of autoimmune blistering skin disorders. A 51-year-old man presented with paraneoplastic pemphigus associated with a hepatic neoplasm. He described an epigastric mass and associated mucositis affecting the orogenital mucosae, as well as the sclerae. Both computed tomography and magnetic resonance imaging demonstrated a 14-cm mass arising from the left lobe of the liver. A liver biopsy showed features of an atypical spindle-cell neoplasm, but a definite diagnosis was not possible. A diagnostic skin biopsy was taken from his outer lip mucosae. Histology showed surface ulceration with an acute inflammatory infiltrate, lichenoid lymphoplasmacytic infiltrate with focal basal vacuolar change, degenerate keratinocytes and adjacent suprabasal acantholysis and spongiosis. Perilesional direct immunofluorescence (DIF) was negative; however, indirect immunofluorescence (IIF) showed intercellular IgG antibodies on transitional epithelium with a high titre of 1 : 800 to rat bladder. These finding were consistent with the suspected clinical diagnosis of paraneoplastic pemphigus. The patient was commenced on oral prednisolone 1 mg kg−1 daily. Topical therapy included budesonide mixed with sweetener applied to the oral mucosae. Following this, a trial of 3 days of intravenous methylprednisolone along with 2% cocaine mouthwash, triple mouthwash (betamethasone, doxycycline and nystatin) and Dermovate® ointment was commenced, with improvement noted in pain, haemorrhage and ulceration. Intravenous immunoglobulin was administered preoperatively. The patient was subsequently transferred to a specialist centre for hepatobiliary surgery and listed for debulking of the liver mass. Postoperatively, he had plasmapheresis, with a noted reduction in mucosal ulceration and significant improvement in pain. Chemotherapy with doxorubicin and ifosfamide was initiated thereafter. PNP is a severe autoimmune blistering disorder characterized clinically by flaccid blisters and erosions. Although much is yet to be understood regarding the pathophysiology of PNP, studies show that the development of autoantibodies to the plakin family and desmogleins 1 and 3 play a particular role in its pathogenesis. In addition to autoantibodies, CD8+ T cells have also been shown to contribute to the development of PNP. In adults, the majority of cases are associated with an underlying haematological malignancy and, rarely, a solid-organ tumour. DIF findings include IgG and C3 deposition along the intercellular and basement membrane zones, while IIF detects autoantibodies to proteins found in transitional or stratified squamous epithelium. As in our case, reports have shown that the DIF can be negative, with one study showing a positive DIF in only 41% of cases. This case highlights the complex diagnostic and treatment challenges practitioners face when dealing with PNP and the patients it affects.

Correlation of clinical, histopathologic, and direct immunofluorescence findings in lesional and nonlesional scalp of frontal fibrosing alopecia and lichen planopilaris – An observational study

Correlation of clinical, histopathologic, and direct immunofluorescence findings in lesional and nonlesional scalp of frontal fibrosing alopecia and lichen planopilaris – An observational study

Direct Immunofluorescence in Cutaneous and Systemic Lupus Erythematosus: A Literature Review

Cutaneous manifestations of lupus erythematosus (LE) have a variety of clinical phenotypes and require proper investigation for diagnosis. Knowledge of the direct immunofluorescence (DIF) technique has improved and played an important role in the diagnosis of cutaneous LE. This review explores and summarizes reported DIF findings of each cutaneous LE variant. Historically, DIF findings of cutaneous LE have revealed deposits of multiple immunoreactants at the dermo-epidermal junction with either linear or granular patterns. Immunoglobulin M is the most common immunoreactant and DIF findings of cutaneous LE variants overlap. Therefore, diagnosis of cutaneous LE requires a combination of monitoring patient history, physical examinations and laboratory studies. This review helps interpret and better understand the application of DIF studies in cutaneous LE.

The Case | A benign reason behind a malignant finding

A 21-year-old man presented to the office for deranged kidney function. He was diagnosed to have C3 glomerulonephritis at the age of 18 years when he presented to his first physician with hypertension. Laboratory parameters showed high serum creatinine (2.7 mg/dl), low serum albumin (2.9 g/dl), low total protein (5.2 g/dl), dysmorphic red blood cells on urinalysis, high 24-hour urine protein (5.7 g/d), low complement C3 (32 mg/dl), and low 50% hemolytic complement (10 U/ml). Kidney biopsy showed a membranoproliferative pattern of injury with 3+ reactivity for complement C3 and significant chronic changes. There was moderate tubulointerstitial fibrosis and 30% of all sampled glomeruli were globally sclerosed. Clinically, there were no signs of atypical hemolytic uremic syndrome and pathologically no evidence of thrombotic microangiopathy. He was started on steroids and mycophenolate mofetil, which were discontinued after 3 months in view of intolerable side effects. Thereafter, ravulizumab, a new complement component C5 inhibitor with a longer half-life, was started and he received 4 infusions (3 doses of 3300 mg and 1 dose of 2700 mg at 8 weekly intervals) until his recent visit to the office. Laboratory parameters at that time showed persistently high serum creatinine (2.3 mg/dl), high 24-hour urine protein (6 g/d), and dysmorphic red blood cells on urinalysis; however, 50% hemolytic complement (40 U/ml) and complement C3 (117 mg/dl) normalized. A repeat kidney biopsy was done in view of no clinical response to therapy, and the direct immunofluorescence findings of pretreatment and post-treatment kidney biopsies are shown in Figure 1.

Concordance of Clinical, Histologic and Direct Immunofluorescence Findings in Patients with Autoimmune Bullous Dermatoses in Vietnam.

Introduction: Autoimmune bullous dermatoses (ABD) represent a heterogeneous group of blistering disorders that may be debilitating with high morbidity. Clinical, histological, and direct immunofluorescence (DIF) studies are essential in establishing an accurate diagnosis of ABD, which is essential for its clinical management. Our study objective was to perform a systematic evaluation of ABD cases in a patient population at an academic medical center in Ho Chi Minh City, Vietnam, and determine the degree of concordance of clinical, histological, and DIF findings in ABD. Methodology: A systematic retrospective cross-sectional study was performed on 92 patients diagnosed with ABD by clinical, histological, and DIF studies at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, between September 2019 and September 2021. The clinical histories, H and E stained tissue sections, and DIF stains were evaluated by pathologists at the University of Medicine and Pharmacy. Results: ABD was evaluated as a whole and subdivided into an intraepidermal blister subgroup and a subepidermal blister subgroup. The analysis of paired diagnostic methods (clinical, histological, and DIF) for concordance with the final diagnosis was performed and showed that there were no statistically significant differences between the paired methods (McNemar’s test, p > 0.05). There was moderate concordance between the clinical, histological, and DIF diagnoses among all ABD cases (Brennan-Prediger coefficient Kappa test, κBP = 0.522, CI = 0.95). In the intraepidermal blister subgroup, the diagnostic accuracies of the histology and DIF stains were comparable to each other, and both were more accurate than a clinical diagnosis alone. In the subepidermal blister subgroup, there was no statistically significant difference in each pair of the three diagnostic methods (clinical, histological, and DIF) (McNemar’s test, p > 0.05). The concordance between the clinical, histological, and DIF diagnoses was high for the intraepidermal blister subgroup (Kappa test, κBP = 0.758, CI = 0.95). However, the concordance between the clinical, histological, and DIF diagnoses was slight for the subepidermal blister subgroup (Kappa test, κBP = 0.171, CI = 0.95). Conclusion: Histological evaluation is highly accurate in the diagnosis of the intraepidermal blister subgroup, but it is not as accurate in the diagnosis of the subepidermal blister subgroup in the Vietnamese patient cohort in which clinical, histological, and DIF studies were performed. DIF stains are a crucial diagnostic tool for ABD in this patient population.

Systemic disease in leukocytoclastic vasculitis: a focus on direct immunofluorescence findings

BackgroundDirect immunofluorescence (DIF) panels are usually ordered for clinically suspected cutaneous vasculitis, but their positivity rate is variable, and their prognostic significance is not clear to date. ObjectiveThe study aims to investigate the systemic involvement rate in leukocytoclastic vasculitis (LCV) patients and the potential clinical and laboratory associations with systemic involvement, including DIF findings. MethodsA retrospective study of patients with histopathologically proven cutaneous LCV examined in the dermatology department between 2013 and 2017 was performed. ResultsOf the 81 patients (mean age, 50.6 years), 42 (52%) were male. The mean time between the appearance of skin lesions and biopsy was 23.1 days, ranging from 2 to 180 days. DIF showed overall positivity of 90.1%, and C3 was the most frequent immunoreactant (82.7%). Any kind of extracutaneous involvement was present in 47 (58%) of patients, with renal involvement being the most frequent (53.1%), followed by articular (18.5%) and gastrointestinal (11.1%) involvement. The presence of renal disease was associated with the detection of IgG in the lesional skin (p = 0.017), and with the absence of IgM in the lesional skin (p = 0.032). There was a significant association between C3 deposition and joint involvement (p = 0.05). Study limitationsThis is a single-center study with a retrospective design. ConclusionDIF seems to be a useful ancillary diagnostic tool in the evaluation of cutaneous vasculitis, but the relationship between DIF findings and systemic involvement needs to be further elucidated due to contradictory data in the current literature.

Clinical and histopathological study of renal biopsy in Nepalese children: A single center experience.

BackgroundGlomerular diseases are important causes of morbidity and mortality among children in developing countries. Renal biopsy is the gold standard for determining histological diagnosis, prognosis, and therapy options. This study aimed to investigate the clinical, histopathological, and direct immunofluorescence findings of renal biopsy results in Nepalese children under 18 years old.MethodsIn this retrospective cross-sectional study, the available data from children who had undergone kidney biopsy between 2016 and the end of 2020 were evaluated. Demographic data, indications of biopsy, histopathologic findings, and direct immunofluorescence findings were collected and presented.ResultsThe mean age of the patients was 12.14 ± 4.07 years. Male/female ratio was 1:1. The majority of biopsy cases were aged between 11–15 years of age. The most common indication for biopsy in children was nephrotic syndrome (68.25%). Lupus nephritis with 28 cases (22.22%) had the highest frequency in overall renal biopsies. Minimal change disease (MCD) with 22 cases (17.46%) followed by Ig A nephropathy with 16 cases (12.69%) were the most frequent primary glomerulonephritis. Lupus nephritis showed full house positivity, and MCD showed full house negativity in all Direct immunofluorescence (DIF) parameters, whereas immunoglobulin A nephropathy showed 100% positivity in Ig A in DIF.ConclusionsNephrotic syndrome was the most common indication for renal biopsy. The most common primary glomerulonephritis was MCD, while secondary glomerulonephritis was lupus nephritis. Clinical data, light microscopy, and direct DIF played an integral role in the overall final diagnosis.

Inflammatory Bowel Disease Presenting With Retiform Purpura.

A 7-year-old girl with sickle cell trait was admitted with inability to bear weight and a painful rash. Examination demonstrated retiform purpura (RP) of the right leg (Fig. 1A) with tenderness. The lesions had worsened despite treatment with cephalexin. Family history was unremarkable. There was no other skin involvement, history of fevers, or abnormalities on exam. Bloodwork was notable for microcytic anemia, elevated ESR, mildly elevated transaminases, and normal INR, albumin, and creatine kinase. MRI showed no muscle, bone, or joint involvement. Sequential cutaneous punch biopsies showed superficial and deep mixed perivascular and interstitial dermatitis without thromboses or leukocytoclastic vasculitis. Direct immunofluorescence findings were nonspecific. Hematologic evaluation included normal protein C and S levels, and mildly elevated d-dimer. Rheumatologic and infectious disease evaluations were also unremarkable. Over the following weeks new purpuric patches appeared, with some developing central duskiness and necrosis (Fig. 1B,C). After being noted to have mild colitic symptoms (PUCAI 25), elevated fecal calprotectin, persistently elevated transaminases, and a positive antinuclear antibody she underwent endoscopy, colonoscopy, and liver biopsy leading to the diagnoses of ulcerative colitis (Fig. 2) and autoimmune hepatitis. Treatment with systemic steroids improved her pain and transaminases, but the rash continued to evolve over the following 3 months developing a central necrotic eschar with surrounding ulceration to the subcutaneous tissue that slowly healed with supportive wound care (Fig. 1C–E).FIGURE 1.: Anterior views of the right thigh on presentation (A), 1 week later (B), 2 weeks later (C), 1 month later (D), 2 months later (E), and 3 months later (F). Purpura (A,B) were not palpable as are observed in cutaneous small-vessel vasculitis. Note the absence of marked purulence (D, E) or cribriform scarring (F) which are observed in pyoderma gangrenosum.FIGURE 2.: Colonoscopy showed gross pancolitis (A) with erythema, edema, friability and microhemorrhages. Histopathologic findings (B) included chronic active colitis with cryptitis (arrow) and abnormal crypt branching (arrowheads) but no granulomata.RP presents as branching purpuric patches and develops when dermal and subcutaneous blood vessels are compromised by vessel wall damage or lumen occlusion causing pain, necrosis, and ulceration (1). Underlying processes include those that damage the vessel wall such as small- or medium-vessel vasculitides, angioinvasive infections, and depositional diseases. RP also results from vessel lumen occlusion due to thrombosis from hypercoagulable states, platelet disorders, and red blood cell occlusion, as well as embolic processes (1,2). Clinically, it can resemble cutaneous small-vessel vasculitis (CSVV) or pyoderma gangrenosum but is differentiated by the lack of palpable purpura or marked purulence, respectively (3,4). Histologically, the vascular origin of RP is deeper than CSVV and it lacks the neutrophilic infiltrate characteristic of pyoderma gangrenosum (3–5). Treatment should address the underlying etiology and include supportive wound care (6). Here, the vaso-occlusive process RP was the presenting feature in a patient with unrecognized inflammatory bowel disease. This may reflect the incompletely understood association between coagulation and inflammation in inflammatory bowel disease that is posited to result from the interplay between a hyperactive coagulation system, decreases in natural coagulation inhibitors, abnormal fibrinolysis, endothelial dysfunction, chronically activated platelets, and systemic inflammation (2,7,8).

A Cross-Sectional Study to Correlate Serum Complement C3 and C4 Levels With Clinical and Pathological Severity in Cutaneous Small-Vessel Vasculitis.

IntroductionThe role of serum C3 and C4 levels as a marker of disease activity in cutaneous small-vessel vasculitis (CSVV) has been sparsely studied, especially in India. The primary objective was to determine the correlation between clinico-histopathological severity and serum C3 and C4 levels in CSVV. The secondary objective was to determine the association between direct immunofluorescence (DIF) findings and serum C3 and C4 levels and clinico-histopathological findings.MethodThis prospective cross-sectional study included all the clinically diagnosed cases of CSVV that satisfied the pathological criteria for CSVV. A clinical disease activity grade and a histopathological severity grade were calculated in all patients (N=50).ResultsSerum C3 and C4 levels (n=44) were diminished in 4.5% of cases. There was no significant correlation between the serum C3 and C4 levels and the clinical and histopathological severity. DIF was positive in 60.0% of cases (n=45), and IgA was the predominant immune deposit (46.7%). No significant association was detected between the DIF findings and the serum C3 and C4 levels, histopathological severity, and clinical disease activity grade. Positive DIF findings were significantly associated with palpable purpura and cutaneous necrosis. A significant association was detected between gastrointestinal involvement and IgA positivity.ConclusionIn CSVV, serum C3 and C4 may not be used as markers of disease severity, and a positive DIF finding may indicate an underlying gastrointestinal involvement.

Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy.

Membranous nephropathy (MN) causes nephrotic syndrome, mostly primary but may be associated with SLE, infections, cancer, or drug. To estimate clinical, serological, light microscopic, and direct immunofluorescence (DIF) findings to differentiate primary and secondary MN. Prospective, cross-sectional, single-center study in a tertiary care hospital. Total 51 cases from September 2019 to February 2020. Blood glucose, urine analysis, urea, creatinine, albumin, cholesterol, HBsAg, Anti HCV, ASO, ANA, MPO ANCA, PR3 ANCA, dsDNA, PLA2R, C3, and C4. Clinical parameters: age, sex, BP, skin lesions, arthralgia, edema, obesity. Renal biopsies examined with H and E, PAS, silver methanamine, MT stains. DIF done with IgG, IgM, IgA, C3c, C1q, kappa, and lambda. Statistical software (Graph Pad PRISM 6) and Chi-square test). Among 51 cases, 25 are primary and 26 are secondary MN with 22 being lupus nephritis, with 2 being post-infectious and the remaining 2 being proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMIDD) with kappa chain restriction. Mean age was 37 ± 12.18 and 30.69 ± 13.92 years for primary and secondary MN, respectively. Significant male preponderance in primary MN. Serum C4 significantly low in secondary MN (15.34 ± 9.59). Microscopic hematuria present in secondary MN. Mesangial and endocapillary hypercellularity are significant in secondary MN. IgG and kappa are significantly intense in primary whereas IgA, C3c, and C1q are significantly intense in secondary MN. Reliable differentiation between primary and secondary MN has important therapeutic implications.

Risk of All-Cause Mortality, Cardiovascular Disease Mortality, and Cancer Mortality in Patients With Bullous Pemphigoid

The role of bullous pemphigoid (BP) in cardiovascular disease (CVD) mortality remains controversial, and analyses of causes of death among patients with BP based on individual data remain lacking. To evaluate the risk of all-cause mortality, CVD mortality, and cancer mortality in patients with BP. This cohort study identified patients who received a diagnosis of and treatment for BP during their dermatology clinic visits at a tertiary medical center in central Taiwan between January 1, 2007, and December 31, 2017. Controls were patients without BP and were individually matched to cases (4:1) according to age, sex, and date of the dermatology clinic visit. Data were analyzed from March 6, 2019, to April 2, 2021. Bullous pemphigoid was confirmed pathologically with typical direct immunofluorescence findings or clinically with typical clinical presentation, positive findings of an anti-basement membrane zone antibody test, and corticosteroid use for at least 28 cumulative days. Mortality outcomes confirmed by the National Death Registry. Of 252 patients with BP and 1008 matched control patients (N = 1260), 685 (54.4%) were men and the median age was 78.0 (IQR, 70.3-84.8) years. Patients with BP had higher CVD mortality at 1 year (20 [7.9%] vs 13 [1.3%]), 3 years (28 [11.1%] vs 24 [2.4%]), and 5 years (31 [12.3%] vs 39 [3.9%]) compared with matched control patients. After adjusting for potential confounding variables, patients with BP had a 5-fold higher risk of CVD mortality at 1 year (hazard ratio [HR], 5.29 [95% CI, 2.40-11.68]), 3 years (HR, 5.79 [95% CI, 3.11-10.78]), and 5 years (HR, 4.95 [95% CI, 2.88-8.51]). Subgroup analyses revealed that the CVD mortality risk associated with BP was higher in patients without a history of hypertension (HR, 7.28 [95% CI, 3.87-13.69]) or CVD (HR, 6.59 [95% CI, 3.40-12.79]) and in patients without prior diuretic use (HR, 5.75 [95% CI, 3.15-10.50]) compared with matched control patients. In addition, all-cause mortality associated with BP was higher in patients without prior corticosteroid use than in control patients (HR 5.65 [95% CI, 4.19-7.61]). The findings of this cohort study suggest that BP was associated with a 5-fold higher risk of CVD mortality, particularly in patients without underlying hypertension or CVD or those without prior corticosteroid or diuretic use. Future studies should investigate the benefits of routine monitoring and timely management of CVD symptoms and signs in patients with BP.

Cutaneous manifestations of lupus erythematosus: a practical clinicopathological review for pathologists.

Accurate diagnosis of connective tissue diseases is often challenging, and relies upon careful correlation between clinical and histopathological features, direct immunofluorescence studies and laboratory work-up. Lupus erythematosus (LE) is a prototype of connective tissue disease with a variety of cutaneous and systemic manifestations. Microscopically, cutaneous LE is classically characterised by an interface dermatitis although other histopathological patterns also exist, depending upon the clinical presentation, location and chronicity of the skin lesions. In this article, we review the clinical, serological, histopathological and direct immunofluorescence findings in LE-specific and LE non-specific skin lesions, with an emphasis upon lesser-known variants, newly described features and helpful ancillary studies. This review will guide general pathologists and dermatopathologists in accurately diagnosing and subclassifying cutaneous LE.

Oral mucous membrane pemphigoid in a group of Thai patients–A 15–year retrospective study

Background/purposeMucous membrane pemphigoid (MMP) is a rare autoimmune disease affecting mucous membrane of the body. Oral involvement is common causing chronic and painful lesions. This study aimed to characterize oral MMP in a group of Thai patients and to analyze treatment regimens. Materials and methodsThe files of patients attending Oral Medicine Clinic were retrospectively studied. Patients fulfilled diagnostic criteria of MMP were included. Chief complaints, medical and dental history, oral manifestations and investigations of individual patients were summarized. Treatment regimens and efficacy were also analyzed. ResultsThere were fourteen patients (age range 33–70 years) with a diagnosis of MMP. The prevalence of oral MMP was 0.51%. The lesions presented as vesicles, blood blisters, erosions, ulcers, erythema, either one type or in combination. Common complaints were chronic painful and bleeding gums. Gingival lesions were found in 13 of 14 patients (92.86%). The most common direct immunofluorescence findings were linear C3 at basement membrane zone (92.31%) followed by linear IgG deposition (84.62%). Most lesions were successfully managed with topical and/or systemic corticosteroids. The average time to control disease was 1.97 months (IQR, 0.69–12.73 months). ConclusionGingival lesions are very common in MMP. Mainstay of treatment is combination of systemic and topical corticosteroids. Multidisciplinary care including oral hygiene maintenance is necessary.

The Frequency and Causes of Subepidermal Gaps or Blisters and the Compliance Rate Between Clinical Diagnosis and Pathology Reports from 2015 to 2019

Background: Skin diseases are the fourth most common cause of human illness, and blisters with different clinical manifestations make a diagnostic challenge. Objectives: This study aimed to evaluate the frequency and causes of subepidermal gaps or blisters, as well as the compliance rate between the initial and final clinical diagnoses based on pathology reports. Methods: In this cross-sectional study, pathology reports of subepidermal blisters or gaps were evaluated in the patients referred to the Razi Laboratory of Rasht from 2015 to 2019. The samples were examined by a pathologist after hematoxylin and eosin staining. The reports included demographic information, clinical differential diagnoses, final diagnosis, direct immunofluorescence findings, and salt split results. Finally, the compliance rate of clinical diagnosis with pathology reports was determined. Results: A total of 183 pathology reports were evaluated, 170 of which contained the final diagnosis. Females were more frequently affected by the disease, and pemphigoid bolus and lichen planus were the most prevalent final diagnoses. The compliance rate between the initial and final diagnoses was 94%. About 37.2% of the reports lacked direct immunofluorescence (DIF) and salt split, and only 42.6% of the samples had undergone DIF examination, while 20.2% had both DIF and salt split. There was no significant association between the compliance rate of the final diagnosis with age, sex, and undergoing diagnostic tests. Conclusions: A high incidence of subepidermal gaps or blisters was seen in middle-aged individuals and females. The compliance rate of the initial clinical diagnosis with the final diagnosis based on pathological reports was high. Our findings emphasize the importance of histopathological examination and the complementary role of direct immunofluorescence and salt split in diagnosis.