Cutaneous manifestations of COVID-19.

The severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has infected patients worldwide. Physicians have increasingly identified cutaneous findings as a significant clinical manifestation of COVID-19. In this review, we describe the clinical presentation, onset, duration, associated symptoms, treatment, and outcome of cutaneous manifestations thus far reported to be related to COVID-19. We have included data from 63 studies and subdivided reported cutaneous manifestations into the categories of viral exanthem, urticarial, vesicular, chilblains/chilblains-like, non-chilblains vasculopathy-related, pityriasis rosea-like, erythema multiforme-like, Kawasaki/Kawasaki-like disease, and others. Physicians should be aware of the known common cutaneous manifestations of COVID-19 and future research is required to better understand the pathophysiology and prognosis of each COVID-19-related skin manifestation.

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

Vascular Assessment of the Lower Extremity with a Chronic Wound.

Peripheral arterial disease (PAD) affects many individuals worldwide and is associated with increased morbidity and mortality. Controversy exists on whether or not to screen asymptomatic patients. Further complicating this is that many patients with a chronic lower extremity wound are often asymptomatic. PAD and traditional noninvasive vascular studies may be inaccurate in providing a correct diagnosis. A review of current and novel vascular assessment modalities along with their benefits and limitations are presented here. A combination of these vascular assessments may help improve accuracy in diagnosis, providing timely care to those patients in need.

Retiform purpura: Workup and therapeutic considerations in select conditions.

In this article we focus on updates in select etiologies of retiform purpura. These causes of retiform purpura, in addition to bacterial or fungal sepsis, disseminated intravascular coagulation, purpura fulminans, and catastrophic antiphospholipid syndrome, are important diagnoses with potential for morbidity and mortality. Important aspects in the pathophysiology, patient demographics and risk factors, updates in the diagnostic workup, histopathology, and treatment of these specific conditions are discussed.

Características clínicas, dermatoscópicas e histológicas de varios casos de vasculitis eosinofílica recurrente cutánea / Clinical, Dermoscopic and Histologic Features of Recurrent Cutaneous Eosinophilic Vasculitis Cases

La vasculitis eosinofílica recurrente cutánea primaria es una enfermedad rara, caracterizada por placas purpúricas, eritematosas y pruriginosas asociadas a edema. Comparamos y analizamos las características clínicas, dermatoscópicas e histológicas de la enfermedad en 4 pacientes de nuestro hospital y en 13 casos de pacientes publicados previamente. Se incluyeron 17 pacientes, con una mediana de edad de 56 años, y una mediana de duración de la enfermedad de 6 meses. En la mayoría de los casos las lesiones fueron generalizadas (47%) o localizadas en los miembros inferiores (41%). Las características histológicas más frecuentes fueron: color purpúrico (71%), edema local (65%), vasculitis necrosante (94%) e infiltración eosinofílica (100%). La mayoría de los pacientes (82,4%) recibió esteroides orales (mediana de la dosis de 30 mg). La vasculitis eosinofílica recurrente cutánea primaria podría ser una entidad clínica infradiagnosticada. El análisis de los pacientes nos permitió proponer algunos criterios diagnósticos para su definición. Recomendamos una estrategia terapéutica con esteroides de alta potencia y dapsona, pudiéndose considerar como el tratamiento de primera línea

Primary recurrent cutaneous eosinophilic vasculitis is a rare condition characterized by pruritic, erythematous, purpuric plaques associated to edema. We compared and analyze the clinical, dermoscopic and histological features of the disease in 4 patients from our hospital and 13 patients published in the literature. Seventeen patients were included, with a median age of 56 yo, a median duration of disease of 6 months. Lesions were most frequently generalized (47%) or localized in lower limbs (41%). The most frequent features were purpuric color (71%), local edema (65%), necrotizing vasculitis (94%) and eosinophil infiltration (100%) in histology. Most of the patients (82.4%) were given oral steroids with a median dose of 30 mg. Primary recurrent cutaneous eosinophilic vasculitis might be an infra-diagnosed condition. The analysis of the patients allowed us to propose diagnostic criteria for the definition of this disease. We suggest a therapeutic strategy with high-potency steroids and dapsone, which might be considered as first-line treatment

Diffuse dermal angiomatosis.

Diffuse dermal angiomatosis (DDA) is a benign and rare acquired, cutaneous, reactive, vascular disorder. We report a rare case of a 43-year-old man who presented with a large (15-cm diameter), indurated, hyperpigmented plaque covering the left buttock for 6 years. This report further discusses DDA with a review of the literature, including its classification, epidemiology, pathophysiology, etiology, histopathology, differential diagnosis, and current therapeutic approaches.

Cutaneous microangiopathy in patients with type 2 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy.

AIMS/INTRODUCTION: To examine the three-dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type 2 diabetes in relation to neuropathy, retinopathy and nephropathy. MATERIALS AND METHODS: The present study enrolled 17 individuals with type 2 diabetes and 16 without. Skin sections were double-immunostained for type IV collagen and VEGF-A or protein gene product 9.5. Projected images from confocal microscopy served to quantify the occupancy rate of subepidermal type IV collagen-immunoreactive microvascular basement membrane area (OR-T4MBM), subepidermal VEGF-A-immunoreactive area and the VEGF/T4MBM ratio, as well as the protein gene product 9.5-immunoreactive intraepidermal nerve fiber density. Reduced intraepidermal nerve fiber density was applied for the diagnosis of neuropathy, fundic ophthalmoscopy and fluorescein angiography for retinopathy, and microalbuminuria or persistent proteinuria for nephropathy. RESULTS: A total of 12 patients with diabetes had neuropathy, 10 had retinopathy and eight had nephropathy. Regardless of the presence or absence of neuropathy, retinopathy or nephropathy, OR-T4MBM was significantly increased in patients with diabetes compared with individuals without diabetes. In contrast, VEGF/T4MBM ratio was significantly decreased in those with neuropathy and retinopathy, as well as in those with and without nephropathy, whereas a trend toward a decreased VEGF/T4MBM ratio was seen in patients without retinopathy, as compared with individuals without diabetes. CONCLUSIONS: The present study is the first report to show that cutaneous microangiopathy, as indicated by subepidermal microvascular proliferation and impaired VEGF expression, appears to occur before the development of overt clinical neuropathy, retinopathy or nephropathy in patients with type 2 diabetes.

Acroangiodermatitis of Mali (Pseudo-Kaposi Sarcoma) Associated with Chronic Venous Insufficiency and Obesity: A Case Report.

INTRODUCTION: Acroangiodermatitis, also known as psesudo-Kapsoi sarcoma, is a rare and benign angioproliferative malady. It presents clinically as purple-colored plaques, patches, or nodules resembling Kaposi sarcoma and is often related to chronic venous insufficiency, arteriovenous malformation of the legs, paralyzed limbs, and residual limbs. Obesity is a risk factor for venous insufficiency and could be related to acroangiodermatitis. CASE REPORT: The authors report a case of acroangiodermatitis of the bilateral legs that was misdiagnosed for 3 years. The diagnosis was confirmed using histopathological and immunohistochemical examinations such as hematoxylin and eosin staining and CD34 immunostaining. Multiple modalities were utilized to treat the wounds, including serial debridement, compression dressings, and silver antimicrobial dressings. CONCLUSIONS: It should be stressed that chronic, nonhealing wounds should be biopsied to obtain a proper diagnosis.

Cutis marmorata telangiectatica congenita and major lower limb asymmetry.

A 39-week-old male newborn presented at birth with atrophic erythematous and purpuric skin lesions, in a typical right-sided segmental distribution. Lesions were persistent and unaffected by rewarming in the postpartum period. Postnatal echocardiogram showed a predominance of the right cavities and an upper atrial septal defect. Cerebral and abdominal ultrasound were normal along with ophthalmological examination. On follow-up, lower limbs asymmetry was noted. The right lower limb was shorter in length and had a smaller diameter. At 6 months, the right lower limb was 1.5 cm shorter than the left, most likely related to nutritive vessels malformations. The discrepancy was even more pronounced at the age of 9 months. This leg-length asymmetry can lead to severe functional limitations in the future.

A case report of cutaneous polyarteritis nodosa in siblings.

Cutaneous polyarteritis nodosa (CPAN) is characterized by a necrotizing vasculitis of small and medium-sized arteries in the skin, which can be associated with fever, arthralgia, myalgia, and neuropathy, but, unlike polyarteritis nodosa (PAN), there is no visceral involvement. CPAN is rare in childhood. We report two siblings who developed CPAN during childhood. Interestingly, both had Mediterranean fever gene (MEFV) mutation, i.e. heterozygous E148Q. They also shared HLA-A24, -DR15 alleles. Simultaneous occurrence of MEFV mutation and HLA alleles with CPAN has never been reported in Japan. These cases could provide some hereditary clue for the development of CPAN.

Vasculopathies, cutaneous necrosis and emergency in dermatology.

Most emergencies in dermatology comprise a variety of entities with a usually benign course. However, vasculopathies and vasculitis are not common, but they could represent respectively 1.9% and 4.4% of these entities according to some studies of Emergency Dermatology Department. They become an important disease which has to be identified early to establish appropriate management and treatment. Some of them are well known, such as the leukocitoclastic vasculitis, Schölein-Henoch, panarteritis nodosa, antineutrophil cytoplasmic antibody associated vasculitis, giant cell arteritis, cryoglobulinemic vasculitis and antiphospholipid syndrome. More frequent vasculopathies are livedoid vasculopathy, pigmented purpuric dermatosis and calciphylaxis. Less common ones are caused by interferon and cholesterol crystal embolization. Others are very infrequent as Degos disease and Sneddon Syndrome. Among the more recently described ones there are deficiency of adenosine deaminase type 2 and crystalglobulinemia. The other group is composed of vasculopathies associated to microorganism as infective endocarditis, septic vasculopathy, aspergillosis, fusariosis, strongiloidosis, ecthyma gangrenosum, lucio phenomenon of leprosy and necrotic arachnidism. Finally, among these entities we can also find diseases associated with proinflammatory stages as disseminated intravascular coagulation, myeloproliferative disorders, intravascular lymphoma, metastasis intravascular. When we face cutaneous lesions characterized by reticulated violaceous lesions, palpable purpura or cutaneous necrosis, a careful clinico-pathological correlation as well as some laboratory or radiological tests are mandatory to further delineate a diagnosis and a proper first line empirical treatment.

Coagulation disorders and their cutaneous presentations: Pathophysiology.

Hypercoagulable states are inherited or acquired predispositions to venous or arterial thromboses that are best understood in the context of the coagulation cascade. Dermatologists can play a critical role in diagnosing and treating patients with hypercoagulable states because cutaneous symptoms may be a presenting manifestation, thereby reducing morbidity and mortality related to these conditions. This review focuses on the epidemiology and pathophysiology of hypercoagulable states, while the accompanying article iterates the basic clinical features, diagnostic testing, and management of patients who have these conditions.

Cutis Marmorata skin decompression sickness is a manifestation of brainstem bubble embolization, not of local skin bubbles.

"Cutis Marmorata" skin symptoms after diving, most frequently in the form of an itching or painful cutaneous red-bluish discoloration are commonly regarded as a mild form of decompression sickness (DCS), and treated with oxygen inhalation without reverting to hyperbaric recompression treatment. It has been observed that the occurrence of Cutis Marmorata is frequently associated with the presence of a Patent Foramen Ovale (PFO) of the heart, and indeed, with a properly executed contrast echocardiographic technique, these patients have an almost 100% prevalence of PFO. Only occasionally, Cutis Marmorata is accompanied by other symptoms of DCS. These symptoms usually are in the form of visual distortions, vertigo, or mild, vague but generalized cerebral dysfunction (such as abnormal fatigue, clumsiness, concentration problems). The pathogenesis of these other manifestations is clearly emboligenic, and we hypothesize that Cutis Marmorata is also a manifestation of gas bubbles embolizing the brain stem: the site of autonomic nervous system regulation of skin blood vessel dilation and constriction. The consequences of this hypothesis are that Cutis Marmorata skin decompression sickness should no longer be considered a mild, innocuous form but rather a serious, neurological form and treated accordingly.

Skin disease in pregnancy.

Skin manifestations during pregnancy are common and diversified. This review will focus on the most important entities to be recognized by obstetricians. These are, on the one hand, physiological changes, where unnecessary investigations should be avoided, and on the other, the specific dermatoses of pregnancy. These develop electively in pregnancy, and they are currently grouped into three disorders: polymorphic eruption of pregnancy, atopic eczema of pregnancy, and pemphigoid gestationis. Arguments for recognition of these are presented including detection of anti-BP180 antibodies. Follow-up and treatment depend on the precise diagnosis. Risks in fetal prognosis may occur in rare pemphigoid gestationis cases.

Cutaneous vasculitis and inflammatory bowel diseases.

Extraintestinal manifestations occur in up to 40% of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Vasculitides are considered rare cutaneous manifestations, but they often represent an important cause of morbidity and a relevant diagnostic issue in IBD. In addition, the increasing use of biological therapies for IBD may also play a pivotal role in the development of vascular disorders of different type. Hence, we provide a complete and in-depth review of the main features of cutaneous vasculitides observed in IBD, with a specific focus on their clinical presentation and possible pathophysiological mechanisms.