Apremilast Use in Severe Psoriasis: Real-World Data from Central and Eastern Europe.

INTRODUCTION: The broad and sustained efficacy of apremilast for psoriasis has been demonstrated in randomized and real-world observational studies. Data from Central and Eastern Europe (CEE) are lacking. Moreover, apremilast use in this region is limited by country-specific reimbursement criteria. This is the first study to report data on the real-world use of apremilast in the region. METHODS: APPRECIATE (NCT02740218) was an observational, retrospective, cross-sectional study assessing psoriasis patients 6 (± 1) months after apremilast treatment initiation. The study aimed to describe the characteristics of patients with psoriasis receiving apremilast, estimate treatment outcomes, including Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), and assess dermatologists' and patients' perspectives on treatment using questionnaires including the Patient Benefit Index (PBI). Adverse event reports were taken from the medical records. RESULTS: Fifty patients (Croatia: 25; Czech Republic: 20; Slovenia: 5) were enrolled. In patients continuing apremilast at 6 (± 1) months, mean (± SD) PASI score was reduced from 16.2 ± 8.7 points at treatment initiation to 3.1 ± 5.2 at 6 (± 1) months; BSA from 11.9% ± 10.3% to 0.8% ± 0.9%; DLQI from 13.7 ± 7.4 points to 1.6 ± 3.2. PASI 75 was reached by 81% of patients. Physicians reported that the overall treatment success fulfilled their expectations in more than two thirds of patients (68%). At least three-quarters of patients reported apremilast had a quite or very high benefit on the needs they identified as being most important. Apremilast was well tolerated; no serious or fatal adverse events were identified. CONCLUSION: Apremilast was effective in reducing skin involvement and improving quality of life in CEE patients having severe disease. Treatment satisfaction among physicians and patients was very high. These data add to the growing body of evidence showing consistent effectiveness of apremilast across the continuum of psoriasis disease severity and manifestations. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02740218.

Atorvastatin-induced Lupus Erythematosus Tumidus: A Case Report and Literature Review.

Lupus erythematosus tumidus (LET) is a rare photosensitive skin disease classified as a separate subtype of cutaneous lupus erythematosus. Clinically, it is characterized by erythematous plaques on sun-exposed areas. Typical histopathological findings are perivascular and periadnexal lymphohistiocytic infiltrates and prominent mucin deposition in the dermis. Treatment is based on photoprotection, topical corticosteroids, and antimalarial drugs. The exact pathogenesis of the disease is unknown. Drugs are considered a minor risk factor for the development of LET. We present a case of a 56-year-old woman who developed LET after starting treatment with atorvastatin. We describe her clinical course and review the literature concerning the cutaneous adverse reactions induced by statin drugs. To our knowledge, this is the first case of statin-induced LET. We conclude that statins can induce LET and that it is important for clinicians to be aware of this potential adverse effect associated with statins.

Skin and gut microbiota dysbiosis in autoimmune and inflammatory skin diseases.

The human body is inhabited by complex communities of microorganisms. Changes in the composition and function of the skin and gut microbiota are linked to various skin diseases. The microbiota is an important modulator of the immune system and thus maintains homeostasis. Conversely, the immune system can also change the composition of the microorganism community. Thus, it is still unknown whether certain skin diseases are caused by primary changes in the local and/or remote microbiota, or whether dysbiosis is only a secondary consequence of the dermatoses themselves. Expanding knowledge of skin and gut microbiota dysbiosis in skin diseases may possibly lead to better understanding of their pathophysiologies and to the discovery of new molecular markers for their earlier diagnosis and targeted treatment; for example, using specific microbes to replace missing ones. This narrative review provides an overview of current knowledge about skin and gut microbiota dysbiosis in psoriasis, atopic dermatitis, hidradenitis suppurativa, seborrheic dermatitis, acne vulgaris, rosacea, and lichen sclerosus.

Purple-brown coalescing macules on the mandibular area of the face.

This patient presented with a 1-year history of violaceous-brown, coalescing reticulated macules on his face, with no similar lesions in other body areas. Laboratory findings were normal and antinuclear antibody test was negative. Histopathological findings included lichenoid tissue reaction and prominent pigmentary incontinence. Click here for the corresponding questions to this CME article.

Palisaded neutrophilic granulomatous dermatitis in a patient with HLA-B27-negative axial spondyloarthritis: a case report and literature review.

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare histopathological pattern belonging to a group of cutaneous granulomatous eruptions that typically manifests with asymptomatic skin-colored, erythematous, or violaceous papules or nodules. PNGD can be triggered by various systemic conditions, including medications and autoimmune and autoinflammatory disorders, as well as malignancies; for example, lymphoproliferative disorders. Therefore, in patients with PNGD an extended diagnostic workup is mandatory as well as follow-up in the case of idiopathic PNGD. To the best of our knowledge, this is the first reported case in the literature of PNGD causally related to a relapse of HLA-B27-negative axial spondyloarthritis.

Cutaneous adverse effects of biologic drugs in psoriasis: a literature review.

Psoriasis is a chronic immune-mediated skin disease that affects 125 million people worldwide. Over the last two decades, biologic drugs have revolutionized the treatment of moderate to severe plaque psoriasis. They act on one or more molecular targets and thus modify or inhibit signal transduction pathways in the pathophysiological process of the disease. This articles summarizes cutaneous adverse effects to biologic drugs used in the treatment of psoriasis. Because they were on the market first, most of the literature covers cutaneous adverse effects of tumor necrosis factor-α (TNF-α) inhibitors, but increasingly more data are also available for adverse effects caused by newer biologics that inhibit the interleukin (IL)-12/23, IL-17, and IL-23 pathways. Some cutaneous adverse effects are general-for example, injection site reactions-whereas others are more class-specific; namely, Candida infections in IL-17 inhibitors. However, because some biologic drugs used in psoriatic patients are also registered for the treatment of certain other immune-mediated diseases such as rheumatoid arthritis, data regarding cutaneous adverse effects come from various sources that differ in quality and often cannot be interpreted without bias.

Mycobacterium marinum hand infection masquerading as tinea manuum: a case report and literature review.

Fish tank granuloma is a rare skin infection caused by Mycobacterium marinum. It occurs after exposure of skin abrasions to contaminated water or infected fish. The majority of M. marinum infections today are fish tank-related. The most common presentation is a solitary nodule, often with sporotrichoid spread. Other presentations do not occur often. The diagnosis is often delayed because of lack of suspicion, nonspecific histopathological findings, and frequently unsuccessful cultivation. Here we present the case of a 37-year-old male with M. marinum skin infection, presenting as erythematous scaling plaques. Because the initial results of laboratory and histopathological examinations were negative for a fungal infection or nontuberculous mycobacteria, the patient was treated empirically with several systemic antibiotics and antifungals without any success. Finally, the diagnosis of fish tank granuloma was confirmed 3 months after the initial presentation of the patient. After the introduction of treatment with rifampicin and clarithromycin, complete clinical remission was observed after 6 months of therapy.

Long-Term Efficacy of Treatment with Intravenous Immunoglobulin in Scleromyxedema.

Scleromyxedema or generalized lichen myxedematosus is a rare depositional disorder. Diagnostic criteria encompass a generalized papular and sclerodermoid eruption, monoclonal gammopathy (paraproteinemia), most often with G-lambda type immunoglobulin, a characteristic microscopic triad (mucin deposition, fibroblast proliferation, fibrosis), and absence of thyroid disease. Many internal manifestations of scleromyxedema have been described to date, leading to high mortality and morbidity. Because the disease is rare, the etiology is not fully understood and there is a lack of well-designed studies, so no optimal treatment exists so far. This paper reports the follow-up on a patient in 5.5-year remission after successful intravenous immunoglobulin therapy 10.5 years since initial diagnosis.

Imiquimod-associated erythema multiforme.

Patients with multiple actinic keratoses are frequently treated with topical agents such as imiquimod, an immune-response modifying agent. Adverse effects associated with imiquimod therapy are mainly limited to the application site and include erythema, crusting, scaling and ulceration. Systemic adverse reactions, such as erythema multiforme are rare. Here we report a case of a 77- years old patient that developed erythema multiforme after treatment of actinic keratoses with imiquimod. Cessation of imiquimod and treatment with local corticosteroids led to rapid regression of erythema multiforme lesions. Residual actinic keratoses were treated with cryotherapy.

Clinical, Histopathological, and Virological Evaluation of 203 Patients With a Clinical Diagnosis of Molluscum Contagiosum.

Molluscum contagiosum (MC) manifests as small, umbilicated papules caused by the molluscum contagiosum virus (MCV). The extent of clinical misdiagnosis of MC is unknown. Combined clinical, histopathological, and virological evaluation of 203 consecutive patients with clinical diagnosis of MC treated at a university hospital during a 5-year period showed the correct clinical diagnosis in 188 of 203 (92.6%) patients. All 15 clinically misdiagnosed MC lesions were histopathologically and virologically confirmed as either common or anogenital warts caused by different human papillomaviruses. The MCV1/MCV2 subtypes ratio was 1.54:1, and the distribution of MCV subtypes differed across patients' age and anatomical location of lesions.

New Insights into the Evolutionary and Genomic Landscape of Molluscum Contagiosum Virus (MCV) based on Nine MCV1 and Six MCV2 Complete Genome Sequences.

Molluscum contagiosum virus (MCV) is the sole member of the Molluscipoxvirus genus and the causative agent of molluscum contagiosum (MC), a common skin disease. Although it is an important and frequent human pathogen, its genetic landscape and evolutionary history remain largely unknown. In this study, ten novel complete MCV genome sequences of the two most common MCV genotypes were determined (five MCV1 and five MCV2 sequences) and analyzed together with all MCV complete genomes previously deposited in freely accessible sequence repositories (four MCV1 and a single MCV2). In comparison to MCV1, a higher degree of nucleotide sequence conservation was observed among MCV2 genomes. Large-scale recombination events were identified in two newly assembled MCV1 genomes and one MCV2 genome. One recombination event was located in a newly identified recombinant region of the viral genome, and all previously described recombinant regions were re-identified in at least one novel MCV genome. MCV genes comprising the identified recombinant segments have been previously associated with viral interference with host T-cell and NK-cell immune responses. In conclusion, the two most common MCV genotypes emerged along divergent evolutionary pathways from a common ancestor, and the differences in the heterogeneity of MCV1 and MCV2 populations may be attributed to the strictness of the constraints imposed by the host immune response.

Oral manifestations of autoinflammatory and autoimmune diseases.

Autoimmune diseases may also be reflected in changes in the oral cavity that represent the first sign of the disease, or they may occur simultaneously with or later in the course of the disease. Oral findings are mostly non-specific, and therefore further investigations are needed to exclude or confirm possible diagnoses. This article presents the most important diseases in this research area, divides them into meaningful groups, and highlights the importance of examining the oral cavity for possible manifestations.

Primary systemic amyloidosis with skin and cardiac involvement: a case report

Primary systemic amyloidosis is characterized by the deposition of insoluble monoclonal immunoglobulin light chains in various tissues and is usually associated with an underlying plasma cell dyscrasia. In the early stage of the disease, dermatological findings can be the only manifestation, as opposed to organ involvement in the later stages. A dermatologist can diagnose amyloidosis early with a skin biopsy stained with Congo red dye and other appropriate investigations. This case report describes a female patient with primary systemic amyloidosis confirmed histologically from a skin biopsy. When the diagnosis was established, cardiac involvement and monoclonal gammopathy were already present. Treatment with bortezomib and dexamethasone was initiated; due to side effects, the treatment was later switched to lenalidomide, which was better tolerated.

Clinical and Demographic Characteristics of Patients with Molluscum Contagiosum Treated at the University Dermatology Clinic Maribor in a 5-year period.

Molluscum contagiosum virus (MCV) is a common skin pathogen in both adults and children. In this prospective study, we clinically evaluated consecutive patients with molluscum contagiosum (MC) who had been examined during a 5-year period at the second-largest dermatology clinic in Slovenia and described their main demographic and clinical characteristics, concomitant diseases, and treatment success. The study included 188 patients, of which 121 (64%) were men and 67 (36%) were women. A total of 135 (72%) patients were adults, with lesions that were most commonly located in the anogenital region (98%) and were probably sexually acquired. Two adult patients were diagnosed with concurrent human immunodeficiency virus (HIV) infection. Fifty-three (28%) patients were children with a mean age of 5.7 years, most commonly presenting with lesions on the torso and extremities (85%). In adults, the infection most commonly occurred in male patients, while in children it was slightly more common in female patients. At presentation, 58% of patients had more than 5 MC lesions. A total of 30% of the included children had concomitant atopic dermatitis. We did not observe an increased occurrence of MCV infection in patients with atopic dermatitis. All patients were treated with curettage of the lesions. The cure rate at the first follow-up visit after 2 months was relatively high (63%), and recurrences were not associated with the number or site of lesions at presentation or with concomitant atopic dermatitis.

Idiopathic eruptive macular pigmentation.

We present the case of a 10-year-old girl with a six months history of disseminated asymptomatic, brown pigmented macules on the trunk and proximal parts of the extremities. The clinical picture, histological findings, and the course of disease were similar to those of idiopathic eruptive macular pigmentation. The cutaneous lesions gradually disappeared over the next two years without any treatment, and no relapse occurred. The knowledge of this disease is important in order to avoid unnecessary treatment as spontaneous resolution of the lesions may be expected within months or a few years. The spontaneous regression without any treatment is an additional diagnostic criterion.