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The article discusses a study which evaluated the proportions of Tregs and Th17 cells in the skin of pyoderma gangrenosum (PG) patients. Topics covered include the results of the immunohistochemistry of Treg and Th17 markers using the monoclonal antibodies anti-CD4, the balance between Tregs and Th17 cells, and the effectiveness of Th17-oriented therapies such as IL-17 antagonists for PG.

To date, 71 patients having the so-called ‘Rowell’s syndrome’ (RS) have been reported in the literature. However, most of them did not show all the clinical and serological features first described by Rowell and co-workers in 1963. Moreover, since then, subacute cutaneous lupus erythematosus (SCLE) has been identified and the diagnostic criteria as well as the clinical features of erythema multiforme (EM) defined. Accordingly several authors have questioned the existence of RS over the past years. In the present paper, the main clinical, histopathological and immunopathological features of both SCLE and EM are described and all of the cases of RS reported in the literature are also reviewed in depth. A real association between discoid LE and EM was present only in a minority of cases and could be considered a mere coincidence. As for other associations, e.g. those between CLE and lichen planus or psoriasis, the coexistence of CLE and EM does not justify the framing of a separate syndrome as suggested by Rowell et al. [ABSTRACT FROM AUTHOR]

Dermatitis herpetiformis is a rare disease that should be considered the cutaneous expression of a gluten-sensitive enteropathy indistinguishable from celiac disease. Dermatitis herpetiformis is often misdiagnosed and to date no guidelines for the management of dermatitis herpetiformis have been published in Literature. The present guidelines have been prepared for dermatologists by the Group for Cutaneous Immunopathology of the Italian Society of Dermatology and Venereology. They reflect the best data available at the time of preparation and the clinical experience of the authors and the members of the Italian Group for Cutaneous Immunopathology. The diagnosis of dermatitis herpetiformis is established clinically, histologically, immunopathologically and serologically. A gluten-free diet (GFD) is the treatment of choice for patients with dermatitis herpetiformis. Dapsone and/or other drugs should be used during the period until the GFD is effective. In conclusion, the present guidelines provide evidence-based guidance for the diagnosis and treatment of dermatitis herpetiformis. Conflicts of interest None declared. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that evaluates the expression of some proapoptotic and antiapoptotic matrix metalloproteinases (MMPs) in skin lesions of patients with erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Background While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD. Objectives To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate. Methods Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon- γ, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines. Results CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate. Conclusions Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone. [ABSTRACT FROM AUTHOR]

Background Some antihistamines are capable of reducing levels of adhesion molecules in wealing tissues of patients with chronic urticaria (CU). Objectives To determine if 6 weeks of therapy with levocetirizine 5 mg once daily would also induce any decrease in serum levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leucocyte adhesion molecule-1 (ELAM-1) or P-selectin in subjects with CU and chronic autoimmune urticaria. Methods Thirty-six patients with CU (18 with positive and 18 with negative autologous serum skin test) were studied, together with 10 control healthy subjects. All patients received levocetirizine 5 mg daily. Serum soluble cellular adhesion molecule (CAM) levels were determined by immunoenzymatic assay before and after the end of the study period. Disease activity was recorded according to the EAACI/GA2LEN/EDF scoring system. Results After levocetirizine therapy CAM levels decreased in patients with CU, significantly in the cases of ELAM-1 and P-selectin. Patients’ clinical scores improved during regular antihistamine therapy. Conclusions Levocetirizine 5 mg daily demonstrated a broad anti-inflammatory effect in patients with CU. The significant decrease in serum levels of ELAM-1 and P-selectin might reflect the inhibitory activity on neutrophil rolling and extravasation towards inflamed skin. [ABSTRACT FROM AUTHOR]

Topical tacrolimus represents an effective and well-tolerated treatment for atopic dermatitis (AD). Its known effects include reduced production of proinflammatory cytokines and reduced chemokine gradient. We performed lesional skin biopsies on adult patients affected by moderate-to-severe AD. Then, patients were randomized to receive local treatment with tacrolimus ointment 0.1% and hydrocortisone butyrate ointment 1%. On the 21st day of treatment, another skin specimen was taken. Nine patients treated with tacrolimus and seven treated with hydrocortisone successfully concluded the trial. By immunohistochemistry (alkaline phosphatase/antialkaline phosphatase method), we demonstrated that endothelial leucocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 showed different intensities and patterns of expression in untreated AD lesions. Tacrolimus-treated specimens featured a significant reduction of the expression of ELAM-1, VCAM-1 and ICAM-1, while hydrocortisone-treated lesions did not. Inhibition of adhesion molecule expression may represent another selective mechanism of action of topical tacrolimus in AD. [ABSTRACT FROM AUTHOR]

Background Erythema multiforme (EM) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity. Objectives To evaluate further the potential role of certain cytokines and chemokine receptors in cutaneous lesions of patients affected by EM and SJS/TEN and to establish whether such diseases are polarized preferentially towards a T-helper (Th) 1 or Th2 pattern. Methods Biopsy specimens from eight patients with EM, six with SJS/TEN and three healthy controls were stained for immunohistochemical examination using the alkaline phosphatase–antialkaline phosphatase method. The monoclonal antibodies used included those to tumour necrosis factor (TNF)- α, interferon (IFN)- γ, interleukin (IL)-2, IL-5, IL-13, receptor 3 for C-C chemokines (CCR3), receptor 3 for C-x-C chemokines (CXCR3) and CXCR4. Results The SJS/TEN specimens showed significantly higher expression of all the cytokines and chemokine receptors (except CXCR3) tested than the EM specimens. Both lesional series showed significantly higher expression of all the receptors tested than the healthy control specimens, with the sole exception of a lower expression of CCR3 in EM specimens. Comparison between molecules associated with a Th1 or Th2 response revealed a predominance of Th1 response in EM and no significant imbalance between Th1 and Th2 in SJS/TEN. Conclusions We have provided further evidence that TNF- α is strongly expressed in SJS/TEN lesions and therefore it may be involved in the epidermal necrosis featured in such diseases. IFN- γ may play an important role both in EM and SJS/TEN. IL-2, IL-5 and IL-13 may contribute to the cutaneous immunoinflammation in these diseases. Chemokine receptors may be involved strongly in the recruitment of inflammatory cells in lesional skin. In our cases we found a sharp polarization towards a Th1 pattern in EM, while the SJS/TEN lesions showed a mixed Th1/Th2 pattern. [ABSTRACT FROM AUTHOR]

Background Erythema multiforme (EM) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity. Objectives To evaluate the effector role of cellular immunity and the involvement of the CD40/CD40 ligand (CD40L) system in the pathogenesis of EM and SJS/TEN. Methods Biopsy specimens from eight patients with EM and six with SJS/TEN were stained for immunohistochemical examination using the alkaline phosphatase/antialkaline phosphatase method. The monoclonal antibodies used included those to CD1a, CD4, CD8, CD40, CD40L, CD68, Fas, Fas ligand (FasL) and myeloperoxidase. Results The cellular infiltrate in both EM and SJS/TEN lesions was composed mainly of T lymphocytes and CD68+ macrophages. We also detected large amounts of neutrophils. Fas and FasL were very highly expressed in SJS and TEN, but weakly in EM. CD40 staining was strong in all tissue sections; there were numerous CD40L+ cells in SJS/TEN but much fewer in EM. Conclusions Activated T lymphocytes and macrophages, but also neutrophils, are presumably the main triggers of mucocutaneous damage in the SJS/TEN disease spectrum. The Fas/FasL system is significantly expressed in SJS/TEN lesions, but not in EM, where this apoptotic pathway presumably does not play a pivotal role in the epidermal damage. We suggest that the CD40/CD40L system may represent an important pathway of induction of SJS/TEN lesions, while in EM it would contribute to the immunoinflammation only as a second-line mechanism. [ABSTRACT FROM AUTHOR]

There have been only two reports on immunophenotypic characterization in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of the infiltrating CD4+ T lymphocytes.To characterize the immunophenotype of the cells that infiltrate the lesional skin of DM and to evaluate the possible T-helper (Th) polarization Th1/Th2 through detection of specific cytokines, chemokine receptors and markers of cellular activation.Skin biopsy specimens derived from pathognomonic lesions (Gottron's papules and Gottron's sign) of eight patients with DM were immunostained with a large panel of monoclonal antibodies to CD3, CD4, CD8, myeloperoxidase (MPO), eosinophil cationic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)-2, IL-4, IL-5, IL-13, interferon-γ, tumour necrosis factor-α, receptor 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alkaline phosphatase–antialkaline phosphatase method. Control specimens were obtained from five healthy subjects and from six patients with discoid lupus erythematosus.Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was approximately 2·5. A mixed Th1/Th2 profile and higher Th1 cytokine production together with significant staining for CXCR3 were detected. Neutrophil granulocytes were the second most abundant population; eosinophil granulocytes were very poorly represented.Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction between CD40 and CD40L could be an important mechanism of cellular activation in cutaneous immune-mediated inflammation by induction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. There was a significant quantity of MPO+ cells (neutrophil granulocytes) in the inflamed tissue, and they might have a role in sustaining the chronic inflammation. [ABSTRACT FROM AUTHOR]

Abstract: In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-γ), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22–57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-γ showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system. [ABSTRACT FROM AUTHOR]

Background Pemphigoid gestationis (PG), also known as herpes gestationis, is a rare autoantibody-mediated bullous disease, usually associated with pregnancy and the postpartum period. However, infiltrating cells have recently been suggested to also contribute to the pathogenesis of cutaneous lesions. Objectives To evaluate the immunophenotype of T cells infiltrating the PG lesional skin and their prevalent cutaneous cytokine expression, as well as the presence and distribution of mast cells, eosinophils and neutrophils. Methods We performed an immunohistochemical study with a large panel of monoclonal antibodies to CD3, CD4, CD8, HLA-DR, CD25, myeloperoxidase, tryptase, eosinophil cationic protein EG2, human interleukin (IL)-2, -4, -5, -8, interferon (IFN)-ϒ, and granulocyte--macrophage colony-stimulating factor using the alkaline phosphatase--antialkaline phosphatase procedure on lesional skin of seven patients with PG. Skin from four subjects with pruritic urticarial papules and plaques of pregnancy and three additional healthy donors were used as controls. Results The findings indicate that there is a T-cell population with a prevalent T-helper (Th) 2 phenotype in the lesional skin of PG subjects. We also found a number of eosinophils and neutrophils with clear signs of activation. Conclusions These data suggest that an inflammatory infiltrate is involved in the production of PG bullous lesions. In particular, we assume that the Th2 cells might be implicated in the very early stages of autoimmune response and may exercise a broad influence in blister formation in this disease. [ABSTRACT FROM AUTHOR]

We retrospectively studied 132 patients with dermatomyositis; 84 had idiopathic, 30 paraneoplastic, 5 juvenile and 13 amyopathic forms of the disease. The commonest features were macular erythema, heliotropic erythema and Gottron's papules. Flagellate erythema occurred in 5 % of patients with idiopathic dermatomyositis and correlated with the disease activity. Necrotic lesions were also found in this group of patients but did not always signal malignancy. The prevalence of malignancy was high (23%). Raynaud's phenomenon occurred in 10.6% of patients, also in those with malignancy. Dysphagia, interstitial lung disease and arthralgias affected 20%, 8% and 40% of patients, respectively. Anti-Jo-1 antibodies were found in 5% of patients with idiopathic dermatomyositis and low titre ANA in 1/3 of patients. ANA did not correlate with the disease activity. We confirmed the data from the literature, but no cutaneous sign, constitutional symptom or circulating antibody was found marking a particular subtype of the disease. [ABSTRACT FROM AUTHOR]

We have evaluated the incidence of lupus erythematosus (LE)-specific skin disease in 186 patients with LE, seen retrospectively over a 10-year period at our Dermatology Department and determined the correlation of LE-nonspecific skin disease in patients with systemic involvement. Chronic cutaneous LE (CCLE) with classical discoid lesions (localized, 70%; generalized, 30%) was the most common cutaneous manifestation (72.5%). Subacute cutaneous LE (SCLE) represented only 8% of LE skin disease (annular-polycyclic type, 73%; papulo-squamous type, 27%). Acute cutaneous LE (ACLE) was detected in 15% of our patients: the butterfly erythema was the most frequent skin lesion (96%) while only one case of bullous LE and one case of widespread maculo-papular eruption in association with malar erythema were demonstrated. In 8 patients no LE-specific skin lesions (lupus sine lupo) were found. Le-nonspecific skin lesions were found in 31% of our patients with systemic LE (SLE): Raynaud's phenomenon was found in 23/58 (39.6%), cutaneous small vessel leukocytoclastic vasculitis in 8/58 (13.7%), nonscarring alopecia in 18/58 (31%), lupus pernio in 6/58 (10.3%), hemorrhagic lesions in 4/58 (6.8%), livedo reticularis in 5/58 (8.6%), mucosal ulcers in 3/58 (5.1%) and periungual telangiectasia in 12/58 (20.6%) SLE patients. Le-nonspecific skin lesions are detected only in patients with SLE and usually in the active phases of the disease. Lupus (2000) 9, 417–423. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyse the different immunoreactants at the dermo–epidermal junction (DEJ) of patients with cutaneous lupus erythematosus (CLE). Sun-protected non lesional (SPNL) skin biopsies from 65 patients with specific cutaneous manifestations of LE and from 18 patients with other dermatologic diseases were tested using the direct immunofluorescence (DIF) technique. Nineteen out of 65 patients with CLE were affected by systemic LE (SLE). We used the conventional chi-squared test to analyse statistical differences between CLE–SLE and CLE–non-SLE groups in the immunological composition of lupus band test (LBT). C[sub 3] was the most common component while IgM were the most frequent immunoglobulins (Igs) of LBT in LE patients. No immunoreactants could be demonstrated at the DEJ in patients with other dermatologic diseases. No statistical differences could be found between CLE–SLE and CLE–non-SLE groups as regards the detection of the different immunoreactants at the DEJ. A positive LBT (even for the presence of only one immunoreactant at the DEJ) performed on SPNL skin represents a useful and specific criterion to distinguish patients with lupus erythematosus (LE) from those without LE. We also believe in a prognostic value of a positive LBT on SPNL skin when the deposition of at least two immunoreactants is demonstrated, and especially if the deposits are composed of IgG. [ABSTRACT FROM AUTHOR]

Persistent hypereosinophilia, cardiac involvement and a recurrent erythematous-papular pruritic eruption histologically characterized by eosinophilic spongiosis are described in a 77-year-old man. This condition, suggestive of "idiopathic" hypereosinophilic syndrome, represented the prodromic phase of atypical bullous pemphigoid, which manifested 7 months later. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about a study which reveals that serum interleukin-13 levels are increased in patients suffering from Stevens-Johnson syndrome or toxic epidermal necrolysis but not in those with erythema multiforme.

Introduction: Dermatitis herpetiformis (DH) is a chronic, pruritic, gluten‐induced skin disorder characterized by subepidermal granular IgA deposition and a variable degree of enteropathy identical to that seen in coeliac disease. So far, there has been no European consensus about the management of DH. Methods: The guidelines were created by small subgroups of a guideline committee consisting of 26 specialists from various medical fields and one patients' representative. The members of the committee then discussed the guidelines and voted for the final version at two consensus meetings. The guidelines were developed under the support of the European Academy of Dermatology and Venereology (EADV) and in collaboration with the European Dermatology Forum (EDF). Results: The guidelines summarize evidence‐based and expert‐based recommendations (S2 level) for the management of DH (see Appendix). Conclusion: These guidelines will improve the quality of management of DH and support dermatologists in their diagnostic and therapeutic decisions. [ABSTRACT FROM AUTHOR]

The article discusses a study on cutaneous lesions of lupus erythematosus (CLE) and dermatomyositis (DM). The study involves immunohistochemical examination of six patients with DM, five patients with subacute CLE (SCLE) and five patients with discoid CLE (DCLE). Furthermore, the result shows an abnormal increase in apoptotic phenomena on cutaneous lesions of DM and CLE, and it suggests that Fas and Fas ligand (Fas-L) may have an important role in inducing death of basal keratinocytes in DM.

The article presents a case study of a 69-year-old white man diagnosed with a squamous cell carcinoma of the lung and treated with neoadjuvant chemotherapy. The study administered adjuvant cycles of cisplatinum and gemcitabine over the following year. Histological examination showed an interface dermatitis with prominent individual cell necrosis with confluent necrosis in the epidermis. It also diagnosed the subacute cutaneous lupus erythematosus (SCLE) and administered intravenous immunoglobin.

A letter to the editor is presented in response to the article "A Case of Natural Killer Cell Monoclonal Expansion During Efalizumab Treatment in a Patient With Psoriasis" in the previous issue.

A letter to the editor is presented in response to the article "Epidermal interleukin-8 and its receptor CXCR2 in drug-induced toxic epidermal necrolysis" by P. Paquet, C. Ribbens, and GE Piérard in the November 2007 issue.

A letter to the editor is presented in response to the article related to oral diseases.

A letter to the editor is presented regarding a case of linear immunoglobulin A disease presenting as prurigo nodularis in a 57-year-old white woman.

The article analyzes the composition of the cellular infiltrate and the expression of markers of cell activation such as the Fas/Fas ligand in erythema multiforme (EM) and the Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) spectrum. Researchers investigated the involvement of CD40 and CD40 ligand (CD40L) in EM and SJS/TEN, suggesting that CD40/CD40L system activation may represent an important pathway of induction of cutaneous lesions in SJS/TEN.

Presents a response by the authors to a letter to the editor about their article "Evidence for a Role of Type I Interferons in the Pathogenesis of Dermatomyositis," in a previous issue.

Describes the tissue transglutaminase antibody assessment in dermatitis herpetiformis (DH). Association of DH with gluten-sensitive enteropathy; Detection of circulating immunoglobulin A autoantibodies to endomysium in DH and coeliac disease; Details on the formation of gliadin.

A letter to the editor is presented in response to the article "Prurigo as a symptom of atopic and non-atopic diseases: aetiological survey in a consecutive cohort of 108 patients," by A. Iking and colleagues in the 2012 issue.

A letter to the editor is presented in response to the article "The Lupus Band: Do the Autoantibodies Target Collagen VII" that was published in the previous issue.

Background No data are available as to the phenotype of circulating lymphocyte subsets in pyoderma gangrenosum ( PG). Aim To analyse the expression of different chemokine receptors associated to T-helper (Th)1 ( CCR5), Th2 ( CCR4) and Th17 ( CCR6), as well as the regulatory T-cell subset (Treg) and dendritic cell polarization in the blood of newly diagnosed untreated PG patients. Materials and methods Multi-parameter flow cytometry was performed on blood samples from 10 PG patients collected at first diagnosis among centres belonging to the Italian Immuno-pathology Group. Blood samples from 10 age- and sex-matched healthy controls ( HC) were used as controls. Results PG patients are characterized by an over-expression in the blood of the CD4+ CCR5+ and CD4+ CCR6+ and a down-regulation of CD4+ CCR4+ counts with respect to healthy subjects. Moreover, they show increased levels of myeloid derived dendritic cells type1 and reduced levels of the Treg CD4+ CD25high FOXP3+ subset. Conclusions The pattern of chemokine expression argues in favour of a Th1 ( CCR5+) and Th17 ( CCR6+) polarization with a down-regulation of Th2 ( CCR4+). [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo‐like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. Objectives and methodology: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence‐based or rely on expert opinion. The degree of consent among all task force members was included. Results: Treatment depends on the severity of BP and patients' comorbidities. High‐potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B‐cell‐depleting therapy and intravenous immunoglobulins may be considered in treatment‐resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. Conclusions: The guidelines for the management of BP were updated. They summarize evidence‐ and expert‐based recommendations useful in clinical practice. [ABSTRACT FROM AUTHOR]

The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life‐threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case‐by‐case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 – May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non‐congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft‐versus‐host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho‐epithelial Kazal‐type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6‐step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin‐subthematic group Ichthyosis. [ABSTRACT FROM AUTHOR]

Classification of the wide variety of autoimmune diseases that can occur before or after the onset of Sjögren’s syndrome (SS) is currently debated within the conventional SS criteria or as primary SS (pSS) developing autoimmune disease or as ‘associated-overlap’ with other systemic autoimmune diseases. There is also debate on whether or not to consider annular polycyclic subacute cutaneous lupus erythematosus (SCLE) and annular erythema associated with Sjögren's syndrome (AESS) as a spectrum linked to Ro-SSA and/or La-SSB auto-antibodies (SSA/SSB auto-ab). We present the case of a 55-year-old female patient, with pSS positive for SSA and SSB auto-ab, who developed chronic relapsing polymyositis and atypical annular non-polycyclic SCLE lesions resembling AESS, which seemed to suggest a common spectrum. While a chronic-progressive polymyositis may be generally accepted as a relatively rare myositis complicating pSS, interpretation of annular lesions of non-systemic SCLE in SS patients might actually be underestimated as pSS skin manifestation likely related to SSA/SSB auto-ab. [ABSTRACT FROM PUBLISHER]

Focuses on the importance of assessing serum antibodies for the diagnosis and follow-up of psoriasis and coeliac diseases. Immunoglobulin A antigliadin antibodies; Antiendomysium antibodies; Role of antitissue transglutaminase antibodies in coeliac disease.

We describe a 23-y-old woman with known systemic lupus erythematosus (SLE) who presented to us with the characteristic maculopapular lupus rash. Although well-known among the LE-specific skin lesions, this acute cutaneous manifestation is rarely reported. [ABSTRACT FROM AUTHOR]

This document is a reply to a previous article titled "New onset of systemic lupus erythematosus following COVID-19 mRNA vaccination." The authors discuss the case of a 26-year-old female who developed lupus two weeks after receiving the second dose of the COVID-19 vaccine. They note that while the patient did not have a history of lupus, her laboratory findings were consistent with an autoimmune preclinical condition that may have been triggered by the vaccination. The authors emphasize the importance of differentiating between latent presentations and inductions and suggest that negative serology may indicate a better prognosis. They also discuss potential mechanisms by which COVID-19 vaccines may trigger autoimmunity. [Extracted from the article]

An association between mixed cryoglobulinaemia (MC) and hepatotropic viruses, chiefly hepatitis C virus (HCV), has been widely reported. The presence of HCV genomic sequences or HCV-related viral proteins in the serum, purified cryoglobulins, peripheral blood mono-nuclear cells and into several tissues has suggested an important triggering role for HCV in MC patients. However, only few reports investigated the presence of HCV in cutaneous vasculitis and its potential pathogenetic role. Biopsies of cutaneous purpuric lesions from 5 MC female patients (aged front 40 to 80 years) were carried out for virological and histopathological evaluation. A leukocytoclastic vasculitis pattern was found in 4/5 subjects, while the presence of HCV RNA was detected in 3/5. In only 3 cases biopsy specimens were sufficient for immunohistochemical and direct immunofluorescence (DIF) studies. Immunohistochemical evaluation was performed by means of alkaline Phosphatase and monoclonal anti-alkaline phosphatase (APAAP) immune-complexes. In the same skin specimen APAAP and DIF findings were compared with the presence/absence of HCV genomic sequences (PCR technique). In 1 MC patient, the detection of HCV-RNA was associated to a prevalent CD8[SUP 4] T suppressor pattern with a perivascular and subjunctional distribution as well as an intense expression of second class (HLA-DR) and intercellular adhesion (ICAM-l ) molecules on basal keratinocytes, endothelial cells and perivascular infiltrate. These findings suggest a marked inflammatory activation that spreads from endothelial cells to keratinocytes and Langerhans cells. In the 2 HCV-RNA negative specimens the scanty immunopathological staining could indicate a residual activity due to the previous inflammatory event triggered by cryoglobulins. The deposition of circulating HCV-containing immune complexes (CIC) in the skin could be the initial pathogenic event for cryoglobulinemic vasculitis; subsequently CIC could spread from the vascular bed to the perivascular tissue and then could be very rapidly eliminated. If confirmed in larger patients' series these findings could definitely demonstrate a direct role of HCV in the pathogenesis UI cryoglobulinemic vasculitis. [ABSTRACT FROM AUTHOR]

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials. [ABSTRACT FROM AUTHOR]

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono‐ or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient‐reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course. [ABSTRACT FROM AUTHOR]

The article offers information on the detection of circulating autoantibodies in mucous membrane pemphigoid (MMP) is challenging. It mentions using normal human oral mucosa (NHOM) as a substrate for indirect immunofluorescence (IIF) instead of normal human skin or salt-split skin resulted in increased sensitivity; and also mentions diagnosis was made upon histopathology consistent with a subepithelial blistering process and direct immunofluorescence.

A cranial CT angiography was performed due to persistence of headache, revealing superior sagittal sinus thrombosis (Fig. A 65-year-old male patient with unremarkable medical history, except for recent administration of the second dose of Vaxvetria (AZD1222) COVID-19 vaccine, was hospitalized for a mucocutaneous eruption occurred 10 days after the injection. Stevens-Johnson syndrome induced by Vaxvetria (AZD1222) COVID-19 vaccine. [Extracted from the article]

Background: Pemphigus encompasses a group of life‐threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first‐line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. Objectives: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. Results: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations. [ABSTRACT FROM AUTHOR]

Reports a case of a patient with hepatitis C virus (HCV) who subsequently developed cutaneous nodular vasculitis and Sjögren's syndrome (SS) in Caucasus. History of the patient; Association of HCV with vasculitis; Role of HCV in the pathogenesis of SS.

Background: Anti‐nuclear antibodies (ANA), anti‐extractable nuclear antigens (ENA) and anti‐dsDNA antibodies are often associated with cutaneous lupus erythematosus (CLE), with variable frequency depending on skin subtype. However, specific data based on large case‐series on the pathogenetic, diagnostic and prognostic meaning of such autoantibodies are still lacking. Objective: To characterize the correlations between CLE subtypes as well as LE‐non‐specific skin lesions and their autoantibody pattern. Methods: Epidemiological, clinical and immunopathological data of 619 Italian patients with CLE and LE‐non‐specific skin lesions were analysed. Differences in age, sex, clinical features and autoantibody profile were evaluated in each LE subgroup. Results: Anti‐nuclear antibodies (P < 0.0001), anti‐dsDNA (P < 0.0001), ENA (P = 0.001), anti‐Sm (P = 0.001), anti‐RNP (P = 0.004) and anti‐histone (P = 0.005) antibodies were associated with SLE. A strong association between ANA (P < 0.0001) and anti‐dsDNA (P < 0.0001) and female gender was also found: positive ANA and positive anti‐dsDNA had a higher prevalence among females. Chronic CLE resulted to be negatively associated with ENA (OR = 0.51, P < 0.0001), anti‐Ro/SSA (OR = 0.49, P < 0.0001) and anti‐dsDNA (OR = 0.37, P < 0.0001). Intermittent CLE resulted to be negatively associated with ENA (OR = 0.50, P = 0.007) and ANA (OR = 0.61, P = 0.025). Subacute CLE resulted to be associated with ENA (OR = 5.19, P < 0.0001), anti‐Ro/SSA (OR = 3.83, P < 0.0001), anti‐Smith (OR = 2.95, P = 0.004) and anti‐RNP (OR = 3.18, P = 0.007). Acute CLE resulted to be strongly associated with anti‐dsDNA (OR = 6.0, P < 0.0001) and ANA (OR = 18.1, P < 0.0001). LE‐non‐specific skin lesions resulted to be significantly associated with systemic involvement. Livedo reticularis was significantly associated with ENA (P = 0.007) and anti‐Ro/SSA (P = 0.036). Palpable purpura and periungual telangiectasia were significantly associated with ANA. Conclusion: According to our findings, some well‐known associations between CLE subtypes and autoantibody profile were confirmed; moreover, specific association between autoantibodies and LE‐non‐specific skin lesions was highlighted. A strict association between anti‐ENA and anti‐Ro/SSA antibodies and livedo reticularis, ANA and palpable purpura, and ANA and periungual telangiectasia was evidenced. [ABSTRACT FROM AUTHOR]

I Editor i Serology for anti-epidermal transglutaminase antibodies (Anti-TG3 Abs) has attracted interest, being inexpensive and non-invasive and could ideally replace skin biopsy for the diagnosis of Dermatitis Herpetiformis (DH).1 The current commercially available ELISA (Elisa kit) for serum Anti-TG3 Abs overall has a good specificity (84-100%)2-4; however, its clinical use is limited due to variable sensitivity (45-100%) and low specificity in Coeliac Disease (CD) patients (47-85%) in whom Anti-TG3 Abs may be present in the absence of DH.2,3,5-7 Here, we developed and evaluated the diagnostic performance of a novel ELISA to quantitatively measure Anti-TG3 Abs. Interestingly, the specificity of the novel ELISA varied when considering CD patients by age and was higher in patients <=25 years (specificity 97%) versus patients >25 years (specificity 55%). [Extracted from the article]

Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Although a number of studies confirmed the central role of innate immunity, only few studies have investigated the possible contributing role of acquired immunity. In particular, no reports concerning T helper type 1 (Th1) and Th2 cells are available as yet. Therefore, 15 patients with PG, five with Sweet's syndrome (SS) and nine skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers interleukin (IL)-12, interferon (IFN)-γ, C-X-C motif chemokine receptor 3 (CXCR3) and C-C motif chemokine receptor 5 (CCR5), of the Th2-related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40 ligand, of IL-15 and the natural killer (NK) cell marker CD56 in skin lesions by immunohistochemistry. Patients with PG and SS showed a higher expression of Th1 markers than HC. Conversely, IL-5- and CCR3-expressing cells were less numerous in PG skin lesions compared to SS ( P = 0·0157 and < 0·0001, respectively). Both CD40 and CD40L were expressed more in PG than in SS and HC ( P < 0·0001 for both). Finally, the number of IL-15+ and CD56+ cells was higher in the skin of patients with PG than in those of SS and HC ( P < 0·0001 for both). Our results suggest that Th2 cells are down-regulated in PG. At the same time, over-expression of the co-stimulatory axis CD40/CD40L amplifies the impairment of the Th1/Th2 balance. Both these findings might explain the most aggressive behaviour of PG in comparison to SS. Moreover, over-expression of IL-15+ and CD56+ cells may suggest a possible role of NK cells in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background Limited data are available on risk factors associated with lichen sclerosus and no data are available on gender differences in genital lichen sclerosus ( GLS). Objective This multicentre study aimed at identifying potential risk factors for GLS, through data collection from a large, mixed-sex sample of patients comparing gender-related differences in relation to data from the general population. Methods This was a cross-sectional study on 729 subjects (53.8% females, 46.2% males) affected with GLS, consecutively observed within a network of 15 Italian dermatology units. The following information was collected: demographic data, anthropometric measures, comorbidities, family history of LS, clinical features and symptoms related to GLS. Results Overweight and obesity, blood hypertension, hypothyroidism and an educational attainment equal or above upper secondary school level were more frequent among the study patients than among the general Italian population. Moreover, a family history of GLS was reported more frequently than expected among GLS patients. These factors were similar in males and females. The disease tended to occur later in females than in males. Conclusions Our findings suggest that metabolic factors, and possibly a sedentary lifestyle, may play a role in GLS pathogenesis in genetically predisposed patients, and that risk profile is similar in males and females despite some difference in the onset of symptoms. [ABSTRACT FROM AUTHOR]