Cutaneous Manifestations and Their Corresponding Dermoscopic Features in Patients with Dermatomyositis.

Introduction: Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the naked eye. Recently, it gained popularity for evaluation of inflammatory skin conditions. In the field of connective tissue diseases, dermoscopy has been used mainly as a simple and accessible substitute of nailfold capillaroscopy. Objectives: The aim of the present study is to expand the application of dermoscopy in patients with dermatomyositis (DM) beyond the usual nailfold examination. A clinico-dermoscopic correlation between clinical signs of skin affection and dermoscopic features is also suggested. Methods: A total of 29 patients with DM were enrolled in this descriptive prospective study, conducted over a 3-year period. Dermoscopy was performed by a DermLite DL1 dermatoscope on polarization mode, attached to One Plus 3T camera. The following skin lesions were examined: periungual affection, scalp DM, Gottron papules, palmar papules, poikiloderma and auricular changes. Results: Dermoscopy detected predominantly advanced nail fold capillary changes - giant capillaries (79%), microhemorrhages (46%) and avascular areas (25%). The most prevalent trichoscopic features were enlarged tortuous capillaries (64%), interfollicular scales (50%) and peripilar casts and tufting (36%). Among the other skin lesions assessed in this study - Gottron papules were present in 20 patients, poikiloderma in 11, palmar papules in 4 and auricular lesions in 4 patients. Conclusions: The use of dermoscopy for clinical evaluation of skin lesions in DM enhances diagnostic accuracy and elucidates poorly known characteristics of the disease.

Cutaneous manifestations of aortoiliac occlusive disease: two cases and review of the literature.

Aortoiliac occlusive disease (AIOD) is non-inflammatory obstructive vasculopathy commonly affecting patients with advanced atherosclerosis, diabetes mellitus, or elevated cholesterol levels, and subjects with other risk factors such as cigarette smoking.Two Caucasian patients (a 55-year-old woman and a 56-year-old man), with ulcerous cutaneous lesions of AIOD are reported. In both cases, medical history comprises initial lower limb claudication, multiple painful ulcers along the legs and absence of superficial femoral artery pulse. Severe obstruction of both infrarenal aorta and iliac arteries on the left side was demonstrated by contrast angiography and Doppler ultrasonography.The evolution of the disease showed some characteristic findings, including pyoderma gangrenosum-like ulcerations as the initial cutaneous manifestation of AIOD, multiple painful ulcers along the lower extremities, and aorto-iliac occlusive disease due to atherosclerosis.Early diagnosis and surgical reconstruction of vessels in patients with AIOD improved quality of life and limb salvage rates.

CD3Z polymorphisms and promoter hypermethylation in dermatomyositis - the role of cytosine-phosphate-guanine-related single nucleotide polymorphisms.

BACKGROUND: Decreased expression of the T cell receptor (TCR) ζ-chain has been reported in autoimmune diseases. Recent evidence suggests that this deficiency may be due to polymorphisms in the CD3Z (CD247) gene and/or due to promoter hypermethylation. METHODS: Altogether 131 subjects - 36 with dermatomyositis (DM) and 95 healthy controls were genotyped for rs1052230 G > C and rs1052231 T > A polymorphisms using TaqMan assay. The rs840015 G > A polymorphism was analyzed by direct sequencing. The promoter methylation status was analyzed by Sanger sequencing of bisulfite converted DNA. RESULTS: The rs1052230GC genotype and C allele and the rs1052231TA genotype and T allele were found to correlate with photosensitivity as well as the rs1052230C/rs1052231T haplotype. The rs1052231TA genotype was found to be associated with cutaneous disease. The rs840015GG genotype was found increased among patients with DM, leading to increased OR 2.4. On the contrary, the rs840015GA genotype appeared to be protective for the development of DM. From the 11 cytosine-phosphate-guanine (CpG) islands analyzed, only the 8th island showed a difference in its methylation due to the polymorphism rs840015 G > A within this island, as our results suggest. In this way the presence of AA genotype led to no methylation and the presence of the GG genotype was associated with hemimethylation. CONCLUSION: The CD247 rs1052230 G > C and rs1052231 T > A polymorphisms appeared to have a disease-modifying role. The rs840015GA genotype being associated with reduced methylation has a protective role for the development of dermatomyositis and our results suggest that CpG related single nucleotide polymorphisms may play an important role in autoimmunity.

Ultraviolet diagnostic and treatment modalities in the coronavirus disease 2019 pandemic.

Ultraviolet (UV) therapy is an effective and well-tolerated therapeutic method for various dermatologic conditions due to its antiproliferative and immunosuppressive effects. Contemporary phototherapy includes broadband UVB, narrowband UVB, UVA1, PUVA, and excimer laser therapy. The coronavirus disease 2019 pandemic has resulted in the closure of many patient care facilities, including phototherapy units worldwide. Home phototherapy, thalassotherapy, and other UV therapy modalities are an alternative for many patients with chronic dermatoses. We highlighted possible interactions of UV therapy effects and the coronavirus disease 2019 pandemic, and focused on organization and measures against transmission of infections in phototherapy units. Dermatology departments have reopened their units, assessing the risks and benefits for patients, optimizing safety regulations, and adhering to the rules for disinfection.

The role of IL-17 rs2275913, IL-17RC rs708567 and TGFB1 rs1800469 SNPs and IL-17A serum levels in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease and polymorphisms in the cytokine genes and their receptors are thought to influence its development. The aim of this case-control study was to investigate the association of the IL-17A rs2275913, IL-17RC rs708567 and TGFB1 rs1800469 polymorphisms with SLE, its clinical manifestations and the polymorphisms influence on the IL-17A serum levels. Altogether 59 SLE patients with lupus nephritis and 95 healthy controls were genotyped by TaqMan assay. Serum levels were determined by Human IL-17A Platinum ELISA kit. From the studied polymorphisms, only TGFB1 T allele was found to be associated with SLE. Within the patient group, IL-17A GG genotype and TGFB1 -509T allele showed an association with the neurological disease and IL-17RC CC genotype appeared to be associated with lupus arthritis. The IL17A serum levels in the SLE and control groups (7.24 pg/ml and 5.76 pg/ml, respectively) did not show any statistical difference. A weak correlation between IL17A levels and SLEDAI-2K was observed. Our results indicate that IL-17A rs2275913, IL-17RCrs708567 and TGFB1 rs1800469 polymorphisms might play a role in the susceptibility and the clinical manifestations of SLE and IL-17A serum levels should be monitored in the course of the disease. The identification of subsets of SLE with an IL-17-driven disease could improve the therapeutic approach leading to more precise personalized treatment.

Autoimmune connective tissue diseases in the COVID-19 pandemic.

Autoimmune connective tissue diseases are a heterogeneous group of clinical entities sharing a common feature-an impairment of structural components like collagen and elastin, arising by autoimmune mechanisms. Because most patients are on a long-term immunosuppressive therapy, which renders them vulnerable to infections, a new challenge appears in front of physicians in the coronavirus disease 2019 (COVID-19) era. Immune mechanisms are substantial for the control and ceasing of viral infections, and their impairment may cause serious complications; however, data from immunosuppressed transplant patients do not reveal a higher frequency or diseases' severity in those infected by COVID-19. Several immunotherapies used to treat autoimmune connective tissue diseases favorably modulate the immune response of severe acute respiratory syndrome coronavirus (SARS-CoV-2)-infected patients. The present review highlights the problems of susceptibility, severity, and therapeutic options in patients with autoimmune connective tissue diseases during the COVID-19 pandemic. The relationship between autoimmune connective tissue diseases and COVID-19 infection is explained with antiviral protection genes expression, hypercytokinemia, and lymphohistiocytosis/macrophage activation mechanisms. Recommendations concerning therapy for prevention during the pandemic period or in case of concomitant COVID-19 infection are also presented. Clinical trials are ongoing regarding COVID-19 therapy blocking the cytokine response. © 2021 Elsevier Inc. All rights reserved.

Paraneoplastic Dermatomyositis in a Patient with Metastatic Gastric Carcinoma.

Dear Editor, Paraneoplastic dermatomyositis is a distinct clinical variant of dermatomyositis (DM) in which the typical cutaneous features and muscle weakness appear before, simultaneously, or after the diagnosis of an internal malignancy. It occurs in approximately one-third of patients with DM, predominantly adults, after the age of 40 (1). Different neoplasms have been described in association with DM, the most common of which are lung, breast, ovarian, gastrointestinal, prostate, and bladder cancers. The gender distribution of cancer type corresponds roughly to that of the general population (1,2). We report the case of a 58-year-old man who presented with facial heliotrope erythema, periorbital edema, Gottron's papules over the interphalangeal and metacarpophalangeal joints, and Gottron's sign on the elbows (Figure 1). The patient also exhibited some less frequent skin signs of DM, such as shawl sign on the upper back and shoulders and V-sign on the neck and chest. Apart from the rash, he complained of weight loss, adynamia, dysphagia, cough, and scant expectoration, which he reported experiencing over a 3-month period. The muscle involvement consisted of proximal muscle weakness and had appeared a month after the skin rash. The histology of the skin lesion revealed epidermal atrophy, vacuolar degeneration of the basal keratinocytes, and perivascular and periadnexal lymphocytic infiltrate in the upper dermis (Figure 2). Laboratory examination found increased creatine kinase (2822 U/L) and liver enzymes, anemia, and leukocytosis. Screening for antinuclear antibodies and anti-Jo1 autoantibodies were both negative. The diagnosis of trichinosis was excluded via serologic examination. The impaired general condition of the patient led to a prompt paraneoplastic screening. Abdominal sonography detected hepatomegaly. Computed tomography (CT) of the abdomen and pelvis visualized a mass in the distal part of the esophagus, narrowed lumen of the gastric cardia, enlarged gastric lymph nodes, lung and liver metastases, and ascites (Figure 3). The diagnosis of paraneoplastic DM in association with an advanced, metastatic, primary gastric carcinoma was established. Palliative surgery and chemotherapy were proposed to the patient, but he refused both. A systemic therapy with methylprednisolone 60 mg/daily and azathioprine 100 mg/daily was initiated, aiming to alleviate the progressively worsening muscle weakness, but proved ineffective. The patient died two months later of combined respiratory and heart failure. There are multiple prediction factors, such as cutaneous signs, laboratory data, and disease progression, which may direct the physician towards the possibility of paraneoplastic DM. Some atypical cutaneous lesions, such as cutaneous necrosis or vasculitis, hyperkeratotic follicular papules, vesiculo-bullous lesions, and flagellate erythema, are seen more frequently in cancer-associated DM (3,4). None of these were present in our patient. Pruritus is also described as a paraneoplastic sign (5). Some authors consider the increased erythrocyte sedimentation rate and C-reactive protein to be of predictive value for malignancy. Myositis-specific autoantibodies anti-TIF1-γ and anti-NXP-2, among the numerous novel serological markers for DM, are clearly associated with the presence of neoplasia (6,7). Unfortunately, we were unable to test for those autoantibodies. The symptom of dysphagia is a hallmark of paraneoplastic dermatomyositis and usually represents a manifestation of muscle weakness (8). In our case, it was rather a reflection of the endoluminal tumor, although it may also be a combination of both factors. In their study, Bowerman et al. investigated the risk of cancer development in different DM subtypes (9). They included 201 patients with adult-onset DM, 142 of with classic DM and 59 with the clinically amyopathic type. The estimated prevalence of malignancy-associated classic and clinically amyopathic DM were 9.9% and 1.7%, respectively. The authors concluded that older age and classic DM represent independent risk factors for malignancy-associated DM within 2 years of disease onset. Given that early diagnosis significantly impacts prognosis in patients with cancer-associated DM, recent studies support blind screening for internal malignancy (10). Leatham et al. performed a retrospective analysis of 400 patients with DM, finding a total of 53 cancers in 48 patients (some of the patients had two separate neoplasms). Among the group of paraneoplastic DM cases, 17 cancers were diagnosed via purely blind screening in patients with a lack of concerning history or physical examination. The authors claimed that the most informative tests were mammography and CT scanning. The above-mentioned predictive factors for paraneoplastic DM represent a useful tool for the clinician. Although it is generally accepted that patients with DM should undergo some type of cancer screening, there is no consensus regarding methods or frequency. New data suggest that blind screening in asymptomatic patients might be of great importance for early diagnosis and treatment of patients with cancer-associated DM.

Correlation of Disease Activity and Quality of Life of Patients with Psoriasis after Narrow-band Ultraviolet B Therapy.

INTRODUCTION: Treatment with ultraviolet light is a well-established and effective treatment option for mild to moderate psoriasis. The aims of the study were to measure the psoriasis area and severity index (PASI) reduction after narrow-band ultraviolet B (NB UVB) therapy, to evaluate the quality of life before and after treatment using the dermatology life quality index (DLQI), and to compare the clinical effectiveness with quality of life improvement. MATERIAL AND METHODS: Twenty two patients (13 male and 9 female patients), aged between 21 to 70 years (mean age 40±14.65 years) were enrolled in the study. NB UVB treatment was performed with 10 to 25 (mean 18.5; SD 3.39) procedures with cumulative doses of 5 to 19.4 J/cm2. The baseline median PASI score was 20.027 which decreased after therapy to 11.11. More than PASI 50% reduction was achieved in 40.91% of the patients after at least 6 weeks of treatment and the results are highly statistically significant. Quality of life (QoL) assessed using DLQI was found moderately affected by disease pretreatment. NB UVB therapy significantly increased DLQI score in spectrum of 'symptoms and feelings' and 'treatment'. DISCUSSION: The PASI score reduction that we observed after NB-UVB therapy is consistent with the results reported by other authors. Baseline DLQI scores were indicative of moderate QoL impairments associated with disease. At the same time, the reduction of the DLQI index corresponding to improved QoL correlated with the objective clinical symptom assessment. CONCLUSION: Our data suggest that DLQI and PASI indexes are important complementary methods for comprehensive health assessment of patients with psoriasis.

XRCC1 variants do not represent a risk for dermatomyositis and systemic lupus erythematosus in Bulgarian patients.

INTRODUCTION: Systemic lupus erythematosus (SLE) and dermatomyositis (DM) share a similar pathogenesis, and genetic, hormonal, and environmental factors are known to trigger the autoimmune process. The X-ray repair cross-complementing genes (XRCC1 and XRCC3) are known to play a central role in mammalian DNA repair processes. Evidence suggests that impaired DNA repair efficiency is implicated in the development of autoimmune diseases. This case-control study investigates the association between the XRCC1 Arg194Trp (C>T) and Arg399Gln (G>A) polymorphisms and the susceptibility to DM and SLE in Bulgarian patients. METHODS: Altogether 88 patients, 55 with SLE and 33 with DM, and 94 unrelated healthy controls were included in this study. RESULTS: None of the polymorphisms showed an association with SLE, DM, or their clinical parameters. The allele and genotype frequency of the two single nucleotide polymorphisms was similar to those found in other healthy Caucasian populations. CONCLUSIONS: Our results indicate that the XRCC1 rs1799782 Arg194Trp and rs25487 Arg399Gln polymorphisms do not play a role in the susceptibility to SLE and DM.

Rowell's Syndrome Triggered by Omeprazole.

Dear Editor, Rowell's syndrome is a rare disease, characterized by the appearance of erythema multiforme (EM)-like lesions in patients with lupus erythematosus. It was initially reported by Rowell (1) in 1963 and its existence as a separate clinical entity is currently under debate (2,3). A few cases may have been induced by drugs such as systemic antimycotics, antibiotics, anticonvulsants, and more recently proton pump inhibitors (PPIs). CASE REPORT We present the case of a 67-year-old woman with subacute cutaneous lupus erythematosus (SCLE) and EM-like lesions who fulfilled all the criteria for Rowell's syndrome. The patient had lupus arthritis for two years and was treated with oral methylprednisolone 8 mg/day and hydroxychloroquine 200 mg/day. She started receiving 20 mg of omeprazole daily for gastroprotection. The patient also had arterial hypertension with no current treatment, osteoporosis, and an L1 vertebral fracture. The dermatological examination revealed multiple erythematous infiltrated plaques involving mainly the sun-exposed areas (neck, chest, upper back, and shoulders). Cutaneous lesions had an annular or target pattern and a tendency to form hemorrhagic crusts and scales at the margins (Figure 1, A). The mucous membranes were unaffected. Histological examination (hematoxylin and eosin ×200) found epidermal atrophy, vacuolar degeneration of the basal layer, and sparse perivascular lymphocytic infiltrate in the dermis - features corresponding to lupus erythematosus (Figure 2, A). Single eosinophilic necrotic keratinocytes characteristic for erythema multiforme were observed in the epidermis (Figure 2, B). Direct immunofluorescence (IF) from lesional skin showed granular deposits of C3 on the dermo-epidermal junction. Lupus band test from sun-protected, nonlesional skin was negative. On indirect IF a speckled pattern antinuclear antibodies (ANA) with >1:1280 titers were detected. Anti-Ro (>200 U/mL) and anti-La (>200 U/mL) antibodies were also positive. The blood cell count and differential analysis were within reference ranges. The 24-hour urine protein test showed a non-significant proteinuria - 0.36 g/24h. Photo-testing was impossible considering the extent of the skin lesions. The therapeutic approach consisted of increasing the hydroxychloroquine dose to 400 mg/day, substituting PPI with famotidine 20 mg/day p.o. and ceftriaxone 2 g/day for the superinfection with Ps. aeruginosa, which led to a clinical improvement (Figure 1, B). The methylprednisolone dose remained unchanged due to already existing severe adverse effects. DISCUSSION The diagnosis was based on Zeitouni et al.'s classification (4). The three main criteria are as follows: lupus erythematosus, EM-like lesions, and speckled pattern of ANA. Our patient met all three major and one minor criteria, namely the presence of anti-Ro and anti-La antibodies. As for the other minor criteria, RF was negative and no chilblains were found. Although there was a continuous time lapse (more than 1 year) between the initiation of omeprazole intake and the diagnosis of Rowell's syndrome, we suggest that the connection is probable. For instance, the latency differs depending on the incriminated medication in drug induced SCLE. Longer periods are reported for diuretics and calcium blockers, while the time interval is shorter for chemotherapeutic drugs and antimycotics (5). Our suspicions were further confirmed by the fact that the lesions improved promptly within a month after discontinuation of omeprazole and doubling the dose of hydroxychloroquine. PPIs are reported to be a major cause of drug-induced SCLE (6,7). According to Laurinaviciene et al., the most common drugs involved are PPIs, thiazide diuretics, antifungals, chemotherapeutics, statins, and antiepileptics (6). However, very few cases of Rowell's syndrome are found to be drug-related. The culprit drugs include: oral terbinafine (8,9), norfloxacin (10), sodium valproate (11) and esomeprazole (12) (Table 1). CONCLUSION Despite the common clinical and immunological features shared between SCLE, drug-induced SCLE and EM, Rowell's syndrome seems to be a separate entity rather than a coincidental association. Finally, according to our knowledge this case would be the second of Rowell's syndrome due to PPIs.

Genetically Determined TNF-α Secretion Influences the Development of Dermatomyositis and Systemic Lupus Erythematosus.

BACKGROUND: Abnormal secretion of TNF-α is known to play a role in the pathogenesis of dermatomyositis and systemic lupus erythematosus. MATERIALS AND METHODS: In the present study we have analyzed the concentrations of TNF-α in the sera of 30 patients with systemic lupus erythematosus (SLE), 28 with dermatomyositis (DM) and 30 healthy controls by standard ELISA tests. RESULTS: We have found that -308A allele increases TNF-α secretion, while -1031C and -863A alleles decrease it. The -857C/T and 489G/A polymorphisms appeared in strong linkage disequilibrium (D'=0.93) but they did not seem to affect TNF-α secretion. CONCLUSION: TNF-α polymorphisms play a significant role in its secretion and influence the development of DM and SLE.

Intravenous immunoglobulins for treatment of connective tissue diseases in dermatology.

BACKGROUND: Connective tissue diseases are a heterogeneous group of autoimmune disorders affecting not only skin, but also various organs and systems. First-line treatment of connective tissue diseases is systemic steroids as monotherapy or combined with immunosuppressive drugs. Since intravenous immunoglobulins (IVIGs) have been found to be effective for various autoimmune dermatoses, their indications have expanded tremendously. OBJECTIVE: The aim this review article is to highlight the indications, effectiveness, and side effects of high doses immunoglobulins for treatment of patients with connective tissue diseases. METHODS: MEDLINE was searched for prospective clinical studies and case reports on IVIG treatment of lupus erythematosus, dermatomyositis, systemic sclerosis, and mixed connective tissue disease (MCTD). Included studies were analyzed and discussed in terms of the different disease entities. RESULTS AND CONCLUSION: IVIGs are a valuable alternative for treating therapy-resistant patients with lupus erythematosus, dermatomyositis, systemic sclerosis, or MCTD. However, more placebo-controlled clinical studies are needed to evaluate the exact indications and therapeutic regimens.

Inflammatory Myopathies with Cutaneous Involvement: from Diagnosis to Therapy.

The group of idiopathic inflammatory myopathies (IIM) include various disorders of skeletal muscles with or without skin involvement. The most common types are dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). Dermatomyositis subdivides into various clinical forms such as juvenile, amyopathic or paraneoplastic dermatomyositis, scleromyositis, overlap or anti-synthetase syndromes, etc. Recently, numerous new antibodies defining the characteristic clinical phenotype have been described as anti-MDA5 antibodies associated with interstitial lung disease and amyopathic dermatomyositis or anti-TIF1γ antibodies as markers for paraneoplastic dermatomyositis. Moreover, new clinical entities as drug-induced dermatomyositis are presumed, since some medications may induce, or trigger inflammatory myopathies. Knowledge of the complex methods and techniques required to diagnose the disease is of great importance in clinical practice. The variety of clinical variants needs diagnosis because of the differing prognosis and therapeutic modalities.

The Role of CD247 Polymorphisms in Bulgarian Patients with Systemic Lupus Erythematosus.

Decreased expression of the TCR ζ-chain has been reported in several autoimmune and inflammatory diseases. Recent evidence suggests that this deficiency may be due to polymorphisms in the CD247 gene. A total 52 patients with systemic lupus erythematosus (SLE) and 95 healthy controls of Bulgarian ethnicity were genotyped for 837C>G, rs1052230, 844A>T, and rs1052231 using a TaqMan genotyping assay. None of the two polymorphisms appeared associated with the diseases. On the other hand, we have found that the -837GG genotype and the G allele were associated with hematological disease. The -844AA genotype and the A allele appeared associated with the hematological disease as well. The -843AA genotype and the A allele were found to be associated with antinuclear antibody (ANA) tests and immunological disease. An association was found between the -837G allele and arthritis. The AG haplotype was found to be associated with hematological disease, ANA, and immunological disease. Our preliminary data confirm the previous findings that the CD247 polymorphisms are mainly associated with the clinical outcome of the disease and less with susceptibility.