UNASSIGNED: Reactive angioendotheliomatosis (RAE) is a rare, benign, angioproliferative disorder with poorly understood aetiopathogenesis. It is characterised by vascular occlusion that occurs in patients with coexistent systemic or autoimmune disease.
UNASSIGNED: A 60-year-old female presented with an 8-week history of a painful, non-healing, and non-traumatic ulcer on the left thigh. Her past medical history included smoking, peripheral vascular disease (PVD) and previously treated rectal squamous cell carcinoma. The diagnosis of pyoderma gangrenosum with superimposed cellulitis was considered and treatment with oral antibiotics was initiated. Following failure to improve, a biopsy was undertaken leading to the diagnosis of RAE. The patient was referred for urgent consideration of surgical correction of PVD, but was deemed unsuitable for surgical treatment due to a poor performance status. The patient was treated with conservative measures, but her condition rapidly deteriorated and she passed away a few weeks later.
UNASSIGNED: RAE is notorious for mimicking a wide spectrum of diseases. It is an important differential diagnosis to consider in patients with non-healing ulceration and underlying systemic or autoimmune disorders. Our case raises awareness of this rare condition and the mortality that it carries if left untreated. In an attempt to reverse disease progression and mortality, we urge clinicians to attempt surgical correction of PVD even when faced with multiple comorbidities and poor performance status.

Ehlers-Danlos Syndrome (EDS) is a rare connective tissue disorder characterized by mutation in genes that encode or modify collagen. Clinical findings in these patients include skin hyperextensibility, hypermobility of joints, and tissue fragility. Vascular EDS (vEDS) is an autosomal dominant disease typically caused by a mutation in COL3A1, which encodes type III collagen. Presenting signs in the majority of vEDS patients include arterial rupture, uterine rupture, and sigmoid colon perforation. In this case report, the author presents an unusual case of spontaneous small bowel perforation and the creation of a traumatic false passage in the parapharyngeal space during a complicated nasogastric tube insertion in a patient with vEDS.

It seems that the association of two connective tissue disorders, including Marfan syndrome and systemic sclerosis, the first is associated with the loosening of the subcutaneous tissue and the second with its tightening, is a very interesting and controversial paradox at the same time and need finding possible genetic etiologies.

Osteogenesis imperfecta (OI) constitutes a complex connective tissue disorder extending beyond its hallmark bone fragility. This case report explores the intricate diagnostic journey involving an elderly patient with acute chest pain, blue sclerae, and multiple fractures. Despite a thorough cardiac evaluation yielding normal results, the complex medical history and phenotypic markers directed attention toward musculoskeletal factors, underlining the importance of comprehensive diagnostic approaches in hereditary conditions like OI.

The Ehlers-Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification. Recently, a new subtype of EDS called classical-like EDS type 2 (clEDS2), which is caused by biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, was identified. We describe the 11th patient (9th family) with clEDS2, who was complicated by a critical vascular event (superior mesenteric artery aneurysm and rupture). A next-generation sequencing panel-based analysis revealed compound heterozygous variants in AEBP1: NM_001129.5:c.[2296G>T]; [2383dup], p.[(Glu766*)]; [(Glu795Glyfs*3)]. Light microscopic analyses showed increased interfibrillar spaces in the reticular dermis, a disorganized arrangement of collagen fibers, and decreased collagen content. An electron microscopic analysis showed the presence of collagen fibrils with irregular contours (flower-like appearance) and small collagen fibrils. A biochemical analysis showed reduced secretion of type I and type III procollagen. Clinical and molecular features of the current patient and all previously reported patients were reviewed comprehensively. Manifestations noted in most cases (>80%) included skin features (hyperextensibility, atrophic scars, easy bruising, excessive skin/skin folding, delayed wound healing, translucency, piezogenic papules), skeletal features (generalized joint hypermobility, dislocations/subluxations, pes planus), dental abnormalities, and neuromuscular abnormalities. Critical complications, each occurring in a single case, included superior mesenteric artery multiple aneurysm and rupture, aortic root dilation requiring surgery, and bowel rupture. Most AEBP1 variants were predicted or experimentally confirmed to lead to nonsense-mediated mRNA decay, whereas one variant resulted in a protein that was retained intracellularly and not secreted. Clinical, molecular, pathological, and biochemical features of the current patient, as well as a review of all previously reported patients, suggest the importance of the aortic carboxypeptidase-like protein encoded by AEBP1 in collagen fibrillogenesis.

Scleroderma, or systemic sclerosis, is a multisystem autoimmune disorder characterized by hardening and fibrosis of the skin. To date, only a small number of case reports have established a relationship between scleroderma and external cervical resorption (ECR). The aim of this case report is to document the case of a patient with multiple external cervical resorption lesions, who was referred to our unit. A 54-year-old female patient, with a 10-year history of systemic sclerosis diagnosed by her rheumatologist, was referred to our unit regarding extensive ECR. A total of 14 maxillary and mandibular teeth with ECR were detected by clinical examination and cone-beam computed tomography. The characteristic vascularity of resorptive defects with profuse bleeding upon probing was not evident. The patient declined any active treatment owing to the desire to avoid lengthy and unpredictable treatment, which may hasten the loss of her teeth. General practitioners should be aware of the relationship between connective tissue disorders and ECR. Although not well established in the literature, the vascular changes implicated in scleroderma may stimulate the odontoclastic processes involved in ECR.

Osteogenesis imperfecta (OI) is a group of connective tissue disorders with different types of inheritance. OI is characterized by bone fragility and deformities, frequent fractures, low bone-mineral density, and impaired bone micro-architectonics. We described here a case of a one-year-old Tuvan patient with multiple fractures. The disease manifestation occurred first at 12 weeks of age as a shoulder joint bruise, and during the year, the patient sustained 27 fractures. Genetic testing revealed a novel homozygous mutation, c.259_260insCGGCC (p.T87fs), in the SERPINF1 gene. This insertion leads to an open-reading frameshift, and the mutation is not represented in the databases. Mutations in SERPINF1 lead to type VI OI, the clinical picture of which is similar to the disease phenotype manifestation of the patient. Thus, the patient\'s diagnosis was established by finding a novel pathogenic variant in the SERPINF1 gene.

Congenital heart defects and skeletal malformations syndrome (CHDSKM; OMIM #617602) is a rare syndrome characterized by distinctive facial features, congenital cardiac lesions, failure to thrive, and skeletal abnormalities. Hearing impairment, renal, and ophthalmological abnormalities have also recently been reported. We report here the clinical and molecular phenotype of an adolescent male who presented with multisystem involvement suggestive of a connective tissue disorder. The proband presented with the typical dysmorphic, skeletal, and skin findings of CHDSKM. In addition, he had several features not previously documented, including severe and rapidly progressive aortic root dilatation as well gastro-intestinal reflux secondary to esophageal dysmotility with gastric strictures. Genetic testing revealed a recurrent variant in the ABL1 gene, c.1066G>A, p.Ala356Thr. These novel features contribute to the growing body of knowledge regarding this rare and recently described condition as well as lend strength to previous calls for close surveillance of the aortic root from a young age in CHDSKM.

Type IV Ehlers-Danlos syndrome (vascular) is a rare connective tissue disease caused by COL3A1 gene mutation on type III collagen. Clinical presentation is related to vascular fragility and risk of rupture of the arterial wall. Definite diagnosis is given by genetic study and the approach to these patients requires a multidisciplinary team and effective blood pressure control. There is currently only one medication with potential benefit in prevention of cardiovascular events: celiprolol. This article describes the case of a 41-year-old female patient, diagnosed with vascular Ehlers-Danlos syndrome after multiple major cardiovascular events: aortic, coronary and carotid dissections and venous and arterial thrombosis. These required multiple surgical interventions and long-term admission in intensive care units leading to complete functional recovery. This case report seeks to stress the need for an early diagnosis to prevent the severe cardiovascular complications of this rare syndrome.

Erythema ab igne is an uncommon dermatosis characterized by erythematous or hyperpigmented reticular patches that appear after prolonged localized heat exposure. We present three cases of erythema ab igne in pediatric patients who presented in March and April of 2021 and share a history of space heater usage while engaging in remote schooling during the COVID-19 pandemic.