Retinal abnormalities in a patient with cutis marmorata telangiectatica congenita.

Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or in the early postnatal period. Although typically benign, this disease is associated with other systemic abnormalities, including rare ocular alterations, such as congenital glaucoma, cataracts and retinopathy.This manuscript describes a female infant, who presented with generalised livedo reticularis, a band of alopecia and cutaneous atrophy in the temporal region above the coronal suture. The patient was diagnosed with cutis marmorata telangiectatica congenita by a paediatrician, and an ophthalmological evaluation was requested. A funduscopy examination in both eyes showed temporal and superior retina with avascular areas with new vessels, venous dilations and shunts, and no retinal detachments. Given these findings, we performed retinal photocoagulation laser treatment with excellent results.This case report highlights the importance of early ophthalmological evaluation of children with this disease to prevent secondary complications, such as vitreous haemorrhage and tractional retinal detachment.

Cutaneous Collagenous Vasculopathy: A Short Case Series and Literature Review.

ABSTRACT: Cutaneous collagenous vasculopathy (CCV) is a rare and idiopathic microangiopathy of superficial dermal blood vessels. There have been 75 cases described in the literature to date, not including the current report; however, given its clinical similarity to other primary telangiectasias, it is likely to be underreported and underdiagnosed. Here, we describe the clinical and histological features of 2 patients we newly diagnosed with CCV. Both generally fit the profile of prior cases and confirm previously described associations-they both are older White women, have rashes on their lower extremities, and have conditions and medications that are common among other reported cases. However, both are also somewhat atypical, as Patient 1 had symptomatic CCV and Patient 2 had a papular rash. As such, both cases broaden the spectrum of our current understanding of CCV. We also provide a comprehensive review of all published reports of CCV to date and uncover 2 previously unreported associations: one with visceral malignancy, and the other with hypothyroidism. Whether these association are coincidental is worth investigating in future studies.

Clinical study on single-organ cutaneous small vessels vasculitis: a retrospective observational study.

OBJECTIVE: Single-organ cutaneous small-vessel vasculitis (SoCSVV) is an inflammatory skin-limited vascular disease affecting the dermal and/or hypodermal vessel wall. Pathogenetically, idiopathic forms are described, as well as the induction from different triggers, such as infections, drugs, and vaccines. Following the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic outbreak, cases of cutaneous vasculitis induced by both COVID-19 and COVID-19 vaccinations have been reported in literature. The aim of this study is to provide the most recent evidence on new etiological factors, clinical features, and management of the SoCSVV. PATIENTS AND METHODS: We included 42 patients (22 women, 20 men) with SoCSVV and no systemic involvement in the study. The mean age of the patients was 57.3 years. Palpable purpura was the most frequent clinical manifestation (38 cases-90.4%). All patients were diagnosed with leukocytoclastic vasculitis by skin biopsy. RESULTS: The etiological factors were as follows: idiopathic in 9 (21%) patients, drug-related in 19 (45%) patients, COVID-19 infection-related in 5 (12%) patients, post-COVID-19 vaccination in 5 (12%) patients, paraneoplastic in 2 (5%) patients, and drug and infection and sepsis in 1 patient each. Among the drug-related cases, 16 (84%) were antibiotic-related, and most of them were beta-lactam antibiotics. Eosinophilia was present in skin biopsy in the cases related to vaccination and drugs, while intense necrosis and vascular damage in the skin were observed in the cases related to COVID-19 infection, unlike the others. A rapid resolution was observed with the cessation of drugs and short-term steroid treatment for the precipitating factors. CONCLUSIONS: SoCSVV is usually associated with drugs, preceding infections, and vaccines. COVID-19 infection and COVID-19 vaccinations have been reported as new etiological factors. SoCSVV indicates that the disease seems to be a mild, self-limiting illness with a good clinical result.

Vasculitic rash and cerebral emboli in an adolescent with left atrial myxoma.

A previously healthy woman in late adolescence presented to the emergency department with stroke-like symptoms following a two-month history of bilateral foot pain and oedema, accompanied by a macular rash and progressive lower extremity weakness. On further investigation, she was found to have multiple cerebral emboli and a left atrial myxoma fixed to the interatrial septum. The patient subsequently underwent urgent surgical excision of the myxoma. On follow-up, her cutaneous and neurological symptoms were significantly improved. This case suggests that, in the presence of a vasculitic rash without evident or obvious cause, cardiac myxoma should be included in the differential diagnosis.

[Secondary vasculitides]. / Sekundäre Vaskulitiden.

Vasculitides that occur in association with underlying primary diseases are called secondary vasculitides. In the diverse differential diagnostics of vasculitides, a large variety of secondary vasculitides have to be considered. Secondary vasculitides cover the full spectrum of vasculitides, presenting in manifold clinical manifestations. This article provides an overview of systemic diseases and etiological factors, such as infections, drugs, and malignancies, which can be associated with vasculitides. The possible associations with infectious agents are too numerous to be comprehensively covered and are discussed in an exemplary fashion and with a western European focus. Especially in atypical and refractory disease courses, a secondary vasculitis should be considered. In light of the diversity of differential diagnoses and the particular challenges posed by secondary vasculitides, interdisciplinary collaboration is the key for an accurate and early diagnosis as well as for successful treatment management. Treatment of the primary disease should always be prioritized and, if a drug-induced vasculitis is suspected, immediate cessation of the culprit drug is mandatory.

Optimization by mixture design of chitosan/multi-phase calcium phosphate/BMP-2 biomimetic scaffolds for bone tissue engineering.

The modulation of cell behavior during culture is one of the most important aspects of bone tissue engineering because of the necessity for a complex mechanical and biochemical environment. This study aimed to improve the physicochemical properties of chitosan/multi-phase calcium phosphate (MCaP) scaffolds using an optimized mixture design experiment and evaluate the effect of biofunctionalization of the obtained scaffolds with the bone morphogenetic protein BMP-2 on stem cell behavior. The present study evaluated the compressive strength, elastic modulus, porosity, pore diameter, and degradation in simulated body fluids and integrated these responses using desirability. The properties of the scaffolds with the best desirability (18.4% of MCaP) were: compressive strength of 23 kPa, elastic modulus of 430 kPa, pore diameter of 163 µm, porosity of 92%, and degradation of 20% after 21 days. Proliferation and differentiation experiments were conducted using dental pulp stem cells after grafting BMP-2 onto scaffolds via the carbodiimide route. These experiments showed that MCaP promoted cell proliferation and increased alkaline phosphatase activity, whereas BMP-2 enhanced cell differentiation. This study demonstrates that optimizing the composition of a mixture of chitosan and MCaP improves the physicochemical and biological properties of scaffolds, indicating that this solution is viable for application in bone tissue engineering.

Molecular characterization of 13 patients with PIK3CA-related overgrowth spectrum using a targeted deep sequencing approach.

Activating variants in the PIK3CA gene cause a heterogeneous spectrum of disorders that involve congenital or early-onset segmental/focal overgrowth, now referred to as PIK3CA-related overgrowth spectrum (PROS). Historically, the clinical diagnoses of patients with PROS included a range of distinct syndromes, including CLOVES syndrome, dysplastic megalencephaly, hemimegalencephaly, focal cortical dysplasia, Klippel-Trenaunay syndrome, CLAPO syndrome, fibroadipose hyperplasia or overgrowth, hemihyperplasia multiple lipomatosis, and megalencephaly capillary malformation-polymicrogyria (MCAP) syndrome. MCAP is a sporadic overgrowth disorder that exhibits core features of progressive megalencephaly, vascular malformations, distal limb malformations, cortical brain malformations, and connective tissue dysplasia. In 2012, our research group contributed to the identification of predominantly mosaic, gain-of-function variants in PIK3CA as an underlying genetic cause of the syndrome. Mosaic variants are technically more difficult to detect and require implementation of more sensitive sequencing technologies and less stringent variant calling algorithms. In this study, we demonstrated the utility of deep sequencing using the Illumina TruSight Oncology 500 (TSO500) sequencing panel in identifying variants with low allele fractions in a series of patients with PROS and suspected mosaicism: pathogenic, mosaic PIK3CA variants were identified in all 13 individuals, including 6 positive controls. This study highlights the importance of screening for low-level mosaic variants in PROS patients. The use of targeted panels with deep sequencing in clinical genetic testing laboratories would improve diagnostic yield and accuracy within this patient population.

A retrospective study on the direct immunofluorescence findings in pigmented purpuric dermatosis.

BACKGROUND: Pigmented purpuric dermatosis (PPD) is characterized by grouped petechiae, purpuric macules, and pigmentation in the bilateral lower extremities. It runs a chronic and relapsing course. Pathophysiology is poorly understood, but it has been proposed to be an immune-complex disease or capillaritis. This study aimed to determine the incidence and patterns of positive direct immunofluorescence (DIF) findings in patients with clinically and histopathologically confirmed PPD. The association between DIF deposition type and clinical profile was also analyzed. METHODS: Patients with a clinical and histopathologic PPD diagnosis who had undergone DIF studies at a tertiary medical center with attached dermatopathology and immunofluorescence diagnostic centers between January 2002 and December 2021 were included in this study. Data on age, sex, disease duration, comorbidities, and drug intake were collected from medical records. RESULTS: There were 65 patients who satisfied the inclusion criteria. Among them, 58 (89%) had at least one positive finding and 53 (82%) were vascular deposition of immunoglobulin (Ig), complement, or fibrinogen. The most common vascular deposition was fibrinogen (71%) followed by C3 (62%), IgM (18%), IgA (6%), and IgG (3%). Fibrinogen deposition was associated with hypertension (p < 0.03). There was no association between vascular DIF deposition of IgG, IgA, and C3, with age, sex, comorbidities, disease duration, and drug history. CONCLUSION: The most common DIF findings in PPD were vascular deposition of fibrinogen and C3, with or without Ig presence. DIF findings supported a vascular origin in PPD but not an immune complex-mediated disease. Hypertension was associated with fibrinogen deposition and may play a role in its pathophysiology.

Cutaneous polyarteritis nodosa and pulmonary arterial hypertension: An unexpected liaison. A case report.

BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a form of medium-sized vessel necrotizing vasculitis. It is a rare, skin-limited variant of polyarteritis nodosa, characterized by dermal and subcutaneous tissue involvement. The most common findings in cPAN include digital gangrene, livedo reticularis, and tender subcutaneous nodules. However, while limited to the skin, cPAN results in significant morbidity and mortality due to the accompanying skin ischemia and necrosis, such that patients are vulnerable to superinfection. Here, we describe a unique presentation of cPAN associated with pulmonary arterial hypertension (PAH). METHODS: A 78-year-old female presented with digital ischemia and leg ulcers associated with PAH. Skin biopsy showed necrotizing fibrinoid necrosis of the small- and middle-sized vessels of the dermis. A diagnosis of cPAN and PAH was made. The patient was treated with glucocorticoids, vasodilators, and cyclophosphamide. RESULTS: She died due to severe sepsis complications. CONCLUSION: To date, this is the first case report describing the association between cPAN and PAH. In this case, PAH is a complication of the cutaneous vasculitides suggesting that vasculopathy could play a role in the pathophysiology of PAH. However, the underlying pathophysiological mechanisms still have to be firmly established.

Usefulness of Ultrasound in Verrucous Venous Malformation: a Series of 103 Cases.

BACKGROUND: Verrucous venous malformation (VVM), previously called "verrucous hemangioma," is a rare type of vascular malformation. OBJECTIVE: Little is known about the ultrasonographic characteristics of VVM. The present study aimed to show the conventional US and elastographic features of a VVM. MATERIALS AND METHODS: The US findings in 103 patients with VVMs were retrospectively evaluated. RESULTS: On gray-scale ultrasound images, 98 (95.1%) lesions showed subcutaneous fat infiltration from skin across muscle to deep fascia. The other 5 (4.9%) sat in the subcutaneous layer with no skin involvement. Most (96.1%) lesions were hyperechoic. Furthermore, 71.8% of lesions were heterogeneous, 68.9% of which were with ill-defined margins. Calcifications and visible vessels were present in 5.7% and 10.7% of the VVM cases, respectively. By color Doppler ultrasound, all lesions were found with low vascular density and 4.9% showed enhanced blood flow after compression. Venous spectrum was observed in 67.0% of lesions. The elasticity score was 2.66 ± 0.48. CONCLUSION: Diagnosis of a VVM is challenging in the clinic. However, we found that most VVM lesions present distinctive ultrasound imaging characteristics. These ultrasound findings may well contribute to the accuracy of VVM diagnosis, especially in those with the absence of epidermal changes and the lack of dermal involvement.

Punch grafting for the treatment of ulcerated atrophie blanche.

Case report: A 79-year-old woman presented with a large painful ulcer on the lateral aspect of her left leg over a 6-month period and was diagnosed of ulcerated atrophie blanche. On an outpatient basis punch grafting was performed and 3 weeks after, complete epithelization was achieved. Discussion: Ulcerated atrophie blanche is a misdiagnosed disorder with painful lesions and, consequently, a high impact on quality of life. Atrophie blanche describes porcelain-white colored, red-dotted atrophic plaques on legs or feet. It may be due to multiple causes, usually associated with alterations in the microcirculation. All causes of atrophie blanche can be included in the term livedoid vasculopathy, a type of occlusive vasculopathy without vasculitis. Many patients with atrophie blanche and livedoid vasculopathy have also chronic venous insufficiency. Etiological treatment should be prescribed in order to avoid progression of the lesions. In case of chronic venous insufficiency, control of venous hypertension is essential. Without anti-edema measures, superficial, very painful, and resistant ulcers may appear. These ulcers can be considered a wound on scar tissue; therefore, it must be treated as a hard-to-heal wound. As we show in this case, punch grafting is an effective therapeutic alternative for wound closure and pain reduction of ulcerated atrophie blanche.

Annular vasculitic lesions.

Vasculitic skin findings may present with annular morphologies. This group of conditions consists of capillaritis, such as pigmented purpuric dermatoses, and vasculitis, which is often classified by the affected vessel size. Annular vasculitic lesions may be the presenting sign of systemic disease, thus requiring thorough exploration to reach an accurate diagnosis and guide proper disease management. Herein we review the clinical presentation, histopathology, and treatments for cutaneous vasculitic disease that may present with annular lesions.