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Mucous membrane pemphigoid (MMP) with anti-laminin 332 autoantibodies may be associated with malignancies, however, current serological assays have considerable limitations. At present, no commercial test for anti-laminin 332 antibodies is available, restricting the diagnosis to specialized laboratories worldwide. Biochip immunofluorescence microscopy has shown promising results in selected cohorts of laminin 332-MMP patients. Objectives: To detect anti-laminin 332 antibodies by biochip immunofluorescence microscopy in a real-life cohort of MMP patients and compare the results with those from traditional immunoblotting. Sera were obtained from 31 patients with MMP, 28 with bullous pemphigoid, five with pemphigus vulgaris, five with paraneoplastic pemphigus, five with linear IgA bullous dermatosis, and 10 controls, and analysed by biochip immunofluorescence using human cells expressing laminin 332. Immunoblotting was performed using purified laminin 332. MMP involved the oral mucosa in 65%, ocular mucosa in 9%, oral and ocular mucosae extensively in 13% as well as other mucosae in 13% of patients. Concomitant cutaneous involvement was reported in 35% of patients. Three MMP patients had an underlying malignancy. Anti-laminin 332 antibodies were detected in 2/31 (6%) cases by both methods. Based on immunoblotting, both laminin 332-positive sera reacted with α3 chain (in one case also with β3 chain). Both patients with anti-laminin 332 antibodies had extensive mucosal involvement and only one had cancer. Anti-laminin 332 antibodies were not detected in control groups. Biochip immunofluorescence is an appropriate technique to detect anti-laminin 332 antibodies which should be tested in patients with MMP.

Pigmented mammary Paget's disease is a very rare variant of mammary Paget's disease linked to an underlying carcinoma in almost all cases. We present the case of a 62-year-old female patient who came to our attention for the evaluation of a monolateral asymptomatic pigmented lesion of the right nipple, which turned out to be a pigmented mammary Paget's disease unassociated to an underlying malignancy – an extremely rare entity only anecdotally reported in literature. The two main peculiarities of our patient's lesion, the importance of immunohistochemistry in the differential diagnosis and the theories on its pathogenesis are discussed. Further studies are necessary to establish the best treatment options. Click here for the corresponding questions to this CME article.

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.

Lombardy, Italy was one of the most heavily impacted areas in the world during the height of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, quickly becoming the epicenter within Italy. There have been 845,898 cases reported to date July 19, 2021 within Lombardy, accounting for approximately 20% of the cases overall in Italy.1 During the height of the pandemic, concern was raised over the use of biologics for psoriasis as they necessitate some degree of immunomodulation.2.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there has been an open debate on the impact of biological drugs used in the treatment of psoriasis. To define whether patients under treatment with biologics suffer from increased morbidity and mortality from COVID-19, compared to psoriatic patients treated only with topical drugs, we designed an observational monocentric prevalence study recording the personal and clinical data of psoriatic patients, with focus on the presentation of signs and symptoms related to COVID-19 in the period of time ranging from 1 January 2020 to 31 May 2020. A total of 180 patients were enrolled into two groups: 100 patients in the topical therapy group and 80 patients in the biological therapy group. No statistically significant difference was found between the groups regarding the prevalence of COVID-19 infection and symptoms at a bivariable analysis with adjustment for confounders. In conclusion, psoriatic patients under treatment with biologics do not seem to be more susceptible to COVID-19 compared to other psoriatic patients and we suggest not interrupting treatment with biological drugs, even in areas suffering from active outbreaks of the disease.

During the lockdown period most planned visits have been postponed and the number of accesses to Emergency Department (ED) has dramatically reduced. The aim of our study is to analyze the impact of the lockdown on the number, type and severity of Dermatological ED diagnosis. We performed a retrospective review of all dermatological consultations in the ED of IRCSS San Matteo during the lockdown period in Italy (February 22nd ‐ May third 2020) and compared them with those from the same period in 2019. We noticed a sharply reduction in the number of dermatological consultations requested in the ED: from 164 patients in 2019 to 33 in 2020. Some diagnostic categories showed a significant difference with a higher incidence of vasculopathic lesions (0.6% vs 12.1%, P

Objective. Our objective was to characterize the demographic information, clinical features, and laboratory data of patients with dermatitis herpetiformis (DH). Methods. In this multicentre cross-sectional study, consecutive patients with a new diagnosis of DH that referred to nine different Italian centers between 2011 and 2016 were characterized assessing demographic, clinical and laboratory findings, and evaluating gender and age differences across selected variables. Results. A total of 151 patients were included. Among them, 81 (53.6%) were males and 70 (46.4%) were females, with a male to female ratio of 1.2 : 1. The median age at the time of diagnosis was 41 years (range 0–85). Males had a significant longer diagnostic delay if compared to females (9 vs. 3 months, respectively; p=0.01). Direct immunofluorescence was positive in 94.7% of the patients, while duodenal biopsy showed partial to total villous atrophy in 70.1% of patients. All the females resulted positive to at least one of the antibodies tested, while a total of 12 male patients (10.5%) tested negative to celiac-specific antibodies. Female patients had a high rate (14.1%) of autoimmune thyroiditis. Conclusions. Our study confirmed some of the most relevant data regarding DH that have been previously reported in the literature. In addition, we found a reduced diagnostic delay in females with respect to males, possibly related to the higher sensitivity of serologic testing in females with DH compared to males. Finally, we demonstrated that intestinal involvement could be severe in patients with DH and that females should be tested for thyroiditis.

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. OBJECTIVES: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. METHODS: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. RESULTS: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. CONCLUSIONS: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Orofacial granulomatosis (OFG) is the term given to a group of diseases characterized by the presence of non-necrotizing granulomatous inflammation affecting the soft tissues of the orofacial region. Treatment of OFG is often challenging and unsatisfactory. We report on a 32-year-old man with a 2-year history of oedema and swelling of the upper lip without systemic symptoms. The history, clinical features and histopathological findings led to the diagnosis of cheilitis granulomatosa (CG), a disease included in the spectrum of OFG. The patient was treated with oral diaminodiphenyl sulfone (DDS) and clofazimine without success. Oral doxycycline led to a slight improvement of the disease. Because the volume of the upper lip was twice normal size, surgical reduction was performed, followed by administration of oral doxycycline for 3 months. This therapeutic approach led to complete remission, with no recurrence after 3 years.

It is known that individuals with immune dysregulation have an increased risk of non-Hodgkin lymphoma. This association has been proven for pemphigus as well as for other autoimmune disease. We describe the development of cutaneous B-cell lymphoma in two patients affected by long-standing pemphigus vulgaris and pemphigus foliaceus (i.e., characterized by histological and immunopathological features different from those of paraneoplastic pemphigus). In both cases, a therapy with rituximab allowed to achieve the complete remission for the lymphoproliferative disease (never recurred at follow up) and a substantial long-term improvement of the clinical manifestations of pemphigus, although persistent to serological disease and occasional recurrences. We suggest that clinicians should consider that patients with long-standing pemphigus, both vulgaris and foliaceus, may develop primary cutaneous B-cell lymphomas, as shown in our report, and in these cases the treatment with rituximab is elective, providing a therapeutic option for both low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphomas and pemphigus. Nevertheless, as shown in our cases, a constant surveillance for pemphigus is necessary.

We report the case of a female patient who developed a firm, wooden-like, nonpitting edema of the left lower leg after a dermo-hypodermitis. The clinical picture was accompanied by intense pain, strongly impacting the patient's quality of life. A soft-tissue ultrasound demonstrated several millimetric hyperechoic linear lesions whose histopathological examination was conclusive for panniculitis ossificans. A conservative medical management with compression stockings associated with pentoxifylline 800 mg/day was prescribed with improvement of the edema and, in particular, a good pain control. To date, after a 2-year therapy with pentoxifylline, the leg wooden-like edema has substantially improved, despite the persistence of the well-known foci of ossification, and the pain has resolved, conditioning a substantial improvement of the patient's quality of life. No side effect has been observed during the routine follow up. Although there is no unanimous opinion in the literature about the effect of pentoxifylline on bone formation and osteogenic differentiation, pentoxifylline treatment proved to be beneficial in our patient both for the heterotopic ossification process and the pain control. We collected some of the data in literature about pentoxifylline effects and advanced some hypotheses to explain our results. Finally, we suggest that an anti-inflammatory and vasodilators drug such as pentoxifylline could be a possible alternative in heterotopic ossification disorders.

Summary Background Epidermolysis bullosa acquisita (EBA) is a rare autoimmune mucocutaneous bullous disease caused by autoantibodies against type VII collagen, a component of anchoring fibrils that stabilizes dermoepidermal adherence. Type VII collagen is composed of a collagenous domain linked by the noncollagenous (NC)1 and NC2 domains. Objectives To assess the repeatability, sensitivity and specificity of a recently developed enzyme-linked immunosorbent assay (ELISA) for detection of anti-type VII collagen autoantibodies, and to ascertain whether they may be a marker of disease activity in EBA. Methods Using this ELISA, which was able to recognize autoantibodies against the NC1 and NC2 epitopes of type VII collagen, we tested 14 EBA sera, 30 healthy control sera and 113 disease control sera. Results In the EBA sera group, 12 out of the 14 samples were positive in ELISA, with autoantibody titres varying from 7·2 to 127·9 U mL−1 (cutoff value

Background Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. Objectives We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. Methods eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. Results In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. Conclusion Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet.

Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Human infections due to Bartonella spp. are viewed as emerging diseases typical in, although not exclusive to, immunosuppressed patients, in particular those with AIDS, organ transplants and haematological malignancies. We describe four patients, three children and one adult, who developed vegetating papillomatous lesions exclusively on the oral mucosae. They shared a history of haematological malignancy and allogeneic bone marrow/stem cell transplantation, and later developed chronic graft-versus-host disease, also involving the oral mucosae. Histopathologically, the vegetating lesions were characterized by a diffuse neoangiogenesis, granulation-like tissue, and a mixed cell infiltrate predominantly composed of neutrophils. Gram-negative bacteria were found in the endothelial cells of the vessels in the deeper portion of the corium by electron microscopy. In three cases, DNA of B. henselae was detected by polymerase chain reaction (PCR), and confirmed by sequencing of the PCR products. All the lesions healed after systemic antibiotic therapy, although some recurred after months, and regressed again after systemic antibiotic treatment associated with conservative surgical excision.

Primary cutaneous T-cell lymphomas are exceedingly rare in children and adolescents. However, mycosis fungoides (MF) is the most frequent primary cutaneous lymphoma diagnosed in childhood. Two cases of MF in siblings (a 14-year-old boy and his 10-year-old sister) are reported. On the basis of clinical features (histopathological and immunophenotypical findings) a diagnosis of MF patch lesions was made in both siblings. Since recent data in the literature have underlined a high frequency of the HLA-DQB1*03 allele in patients with familial MF (including child patients), the HLA profile of the patients was analysed, indicating the presence of a haplotype (HLA-DQB1*03,*03 in the girl, HLA-DQB1*02,*03 in the boy) corresponding with that described in recent literature. Two rare and exceptional cases of MF in siblings are reported, highlighting the presence of a peculiar haplotype.

Granulomatous slack skin (GSS) represents a rare variant of mycosis fungoides, histologically characterized by a variably deep T helper lymphocytes infiltrate with alteration of the dermal elastic tissue and consequent elastolysis, elastophagocytosis and numerous giant cells. Clinically, a development of unelastic, slack skin, especially on flexural areas, is observed. Hereby, we describe a man with a 12-year history of GSS. In 2002, for practical (limitation of movement, deambulation) and cosmetic reasons, he underwent the surgical excision of loose and sagging skinfold over inguinal area, and, afterwards, of the opposite affected inguinal skin. The surgical treatment of bilateral inguinal hernia with reposition of inguinal dislocated vasculature is also reported. In both cases the excised material confirmed the former diagnosis of GSS and revealed a very deep, muscular infiltrate of neoplastic lymphocytes. One year later, a new excision of GSS on the axillae was made. Now, after 2 years, deambulation keeps improving, although an initial relapse of the inguinal slack skin has been observed.