Cutaneous Telangiectasia Research Articles

Ataxia-Telangiectasia with Novel Splicing Mutations in the ATM Gene

Ataxia-Telangiectasia with Novel Splicing Mutations in the <i>ATM</i> Gene

Hereditary hemorrhagic telangiectasia: The purpose of a clinical case

Introduction: Hereditary hemorrhagic telangiectasia (HHT) or Rendu–Osler–Weber syndrome is a rare autosomal dominant disease, with a prevalence ranging from 1/5000 to 1/10,000 individuals, which causes a generalized fibrovascular dysplasia. While being asymptomatic in the newborn, this disease usually manifests itself in adolescence (62%) with recurrent epistaxis (90%), cutaneous telangiectasias between 20 and 40years (75%), manifestations of liver and lung arteriovenous malformations (AVM) (30 and 45%) and gastrointestinal bleeding (15%) after 40years, presenting neurological involvement in 8 to 20% of the patients.

Widespread Cutaneous Telangiectasias

Widespread Cutaneous Telangiectasias

Widespread Cutaneous Telangiectasias

Moulonguet, Isabelle MD*; Hershkovitch, Didier MD†; Fraitag, Sylvie MD‡ Author Information

Cerebral Abnormalities in Adults with Ataxia-Telangiectasia

Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.

Cutaneous Telangiectasia and Cauda Equina Syndrome

We describe a 72-year-old woman with striking cutaneous telangiectatic lesions that chronologically preceded presentation with cauda equina syndrome. Diffuse large B-cell lymphoma (DLBCL) was confirmed on skin biopsies from plaques on the abdominal wall and left ankle, the possibilities including primary cutaneous DLBCL leg-type or systemic DLBCL. We speculate that this clinical appearance may arise due to lymphatic or vascular congestion resulting from the dense lymphoid infiltrate in this case.

Ataxia telangiectasia patients cannot cause severe Herpes Simplex because of disturbed Herpes simplex virus replication by ATM mutation

Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterized by ocular and cutaneous telangiectasia, hyper sensitivity to ionizing radiation, increased incidence of malignancies, and variable immunodeficiency (high risk of bacterial and viral infection). A-T results from mutations in a single gene (ataxia-telangiectasia, mutated; ATM). ATM responds to a variety of abnormal DNA structures and initiates signaling cascades leading to the DNA damage responses (DDRs). There are no reports of severe herpes simplex in A-T patients, although A-T patients show much higher rate of lethal varicella and other viral infections than healthy individuals.

Telangiectasia macularis multiplex acquisita: a new entity in Chinese populations and an analysis of associated factors

Telangiectasia macularis multiplex acquisita (TMMA) is a rarely documented entity with distinctive clinical manifestation. Most patients are middle-aged adults. It may be associated with other diseases such as hepatitis, diabetes, or cardiovascular diseases. To assess the clinical presentation of TMMA and its association to other systemic diseases, especially the correlation to liver disease, in Taiwan. We identified and retrospectively analyzed clinical criteria-matched and skin biopsy-proven patients from 2002 to 2010 at a single medical center. The clinical criteria for diagnosis of TMMA included: (i) crops of telangiectasia superimposed on erythematous macules symmetrically on bilateral upper arms, possibly extending to the forearms, shoulders, V-shaped area of the anterior chest, back or thighs; (ii) no mucosal or systemic involvement; (iii) not associated with autoimmune diseases, such as lupus erythematosus, dermatomyositis or systemic scleroderma that may induce cutaneous telangiectasia; and (iv) no ataxia or unsteady gait. Twenty-five patients were enrolled in this study. The male-to-female ratio was 19:6. The age of onset was variable, mostly between the third to sixth decades. The V-shaped area of the anterior chest was commonly involved (68%), in addition to the arms (100%). Viral hepatitis was diagnosed in 56.5% of the patients (13/23); 38.9% (7/18) and 50% (9/18) of the patients had diabetes and hypertension, respectively. In addition, 64.7% of the patients (11/17) had dyslipidemia. The pathological reports of most cases showed only mild perivascular lymphocytic infiltration with or without telangiectasia. TMMA should be assigned to a distinct entity with unique clinical manifestation. It has not been well recognized and mostly misdiagnosed as other diseases with telangiectasia. It is important to evaluate the complete liver function tests when TMMA is suspected.

Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were within the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.

La vasculopathie cutanée collagénique : une cause rare de télangiectasies généralisées

Cutaneous collagenous vasculopathy (CCV) is an entity first described in 2000 by Salama and Rosenthal [1]. Because of its rarity, we felt it opportune to report the present case. We describe the case of a 47-year-old woman presenting with widespread telangiectasia distributed symmetrically on the legs, thighs and lower abdomen. The histological and immunohistochemical profile was typical of cutaneous collagenous vasculopathy. Cutaneous collagenous vasculopathy is characterized by generalized cutaneous telangiectasia and unique histopathological features consisting of marked collagen deposition within the vascular wall of the post-capillary venules in the superficial dermis. Its cause remains unknown. The differential diagnosis consists mainly of generalized essential telangiectasia (GET) and telangiectasia macularis eruptiva perstans (TMEP).

Ataxia Telangiectasia (AT) as a radiation sensitivity syndrom and limits of radiotherapeutic intervention

Aims: Ataxia Telangiectasia (AT) is an autosomal recessive inherited ataxia and results from a mutation within the ATM (Ataxia Telangiectasia Mutated)-gene. Functional consequences of this mutation lead to a multisystemic disorder with severe and progressive neurodegeneration, ocular and cutaneous telangiectasia, increased irradiation-sensitivity and a tendency to develop malignant diseases.

Facial telangiectasia: an unusual manifestation of neonatal lupus erythematosus

Neonatal lupus erythematosus (NLE) is an uncommon condition usually associated with maternal anti-Ro autoantibodies. The cutaneous lesions of NLE are usually transient, disappearing about six months after birth, but telangiectasia is a rare complication of NLE which persists. Telangiectasias are small focal red macules and papules created by abnormally prominent capillaries, venules, and arterioles and are a characteristic marker of connective tissue diseases. We report the case of an infant diagnosed with NLE presenting typical annular lesions, positive ANA and positive anti-Ro antibodies. By five months of age, both ANA and anti-Ro antibodies were negative and the annular cutaneous lesions had gradually faded, but small scattered focal red macules appeared on the face, especially in the peri-orbital area and scalp. The cutaneous lupus disappeared but the telangiectasia persisted. We would like to suggest that the diagnosis of NLE should be considered when cutaneous telangiectasias are observed in infants.

Spontaneous Thrombosis of an Orbital Arteriovenous Malformation Revealing Hereditary Haemorrhagic Telangiectasia (Rendu-Osler-Weber Disease)

Hereditary Haemorrhagic Telangiectasia (HHT) is a genetic disorder responsible for cutaneous or mucosal telangiectasia and arteriovenous malformations (AVMs). The most frequent locations are lung and brain. In contrast, orbital AVMs are very rare. We describe a case of symptomatic orbital arteriovenous malformation due to spontaneous thrombosis. A 65-year-old woman was referred for chronic right eye proptosis associated with dilation of conjunctival vessels with a jellyfish pattern. Right visual acuity was 20/40 and intraocular pressure was 40 mmHg. Personal and familial history of recurrent epistaxis, associated with multiple telangiectasia within lips and palate, led to the diagnosis of HHT. Magnetic resonance imaging (MRI) completed with cerebral angiography found a giant and occluded AVM within the right orbit. Other AVMs were also found in brain and chest, confirming the diagnosis. Antiglaucomatous eyedrops were added to reduce intraocular pressure and a steroid therapy was begun. Two months later, visual acuity decreased in the right eye, due to a central retinal vein thrombosis. In conclusion, Most brain or pulmonary AVM can be treated by embolization. By contrast, this treatment in case of orbital location can lead to central retinal artery and/or central retinal vein occlusion, which may also appear as a spontaneous complication of the orbital AVM. Therapeutic management of orbital AVM is thus not standardized, and the balance between spontaneous and iatrogenic risk of visual loss has to be taken into account.

Subcutaneous Calcinosis as Late Sequela of Radiotherapy to the Neck

r g The late adverse effects after radiotherapy to the head and neck region include radiation-induced malignancy and changes in the irradiated tissues, leading to chronic xerostomia, radiation caries, osteoradionecrosis, trismus, and dysphagia. Cranial nerve palsy, ocal cord palsy, sensorineural hearing loss, laryngeal steochondronecrosis, extracranial carotid stenosis, adiation myelopathy, and meningioma have also een reported as head and neck postirradiation seuelae. Radiotherapy can also induce dystrophic calcification by causing tumor necrosis and thus providing the milieu necessary for calcification. Although the data are replete with this form of dystrophic calcium deposition that occurs within the tumor after radiotherapy for various malignancies, heterotopic calcification in the subcutaneous tissue, also known as subcutaneous calcinosis, occurs far less frequently as a part of the late effects of radiotherapy. This form of dystrophic calcification develops after a long period of postirradiation latency. It is limited to the subcutaneous tissue and is linked to the late radiation effects of the overlying skin, notably cutaneous atrophy, telangiectasias, depigmentation, fibrosis, and cutaneous fistulas. The development of subcutaneous alcinosis as a late sequel of radiotherapy was first escribed in 1987 by Vainright et al and has since een described predominantly after chest wall irradition for breast cancer. To our knowledge, this is he first report to document the occurrence of this

Cutaneous angiogenesis in patient with intravascular lymphoma (IVL): A case report

We present a case of widespread cutaneous telangiectasias in a patient with a B-cell intravascular lymphoma most likely representing tumor-induced angiogenesis. The patient presented with a rapid onset of large cutaneous telangiectasias and skin edema, followed by the development of multiorgan failure. We describe difficulties with the ante-mortem diagnosis in the patient with predominant, clinically observed, skin lesions. The patient had disseminated disease involving many organs with a rapidly fatal outcome. The final diagnosis of intravascular malignant lymphoma (IVL) was established post-mortem after morphological and immunohistochemical studies of the autopsy material.

Cyclophosphamide: A Novel Treatment of Gastric Antral Vascular Ectasia Associated with Systemic Sclerosis?

Systemic sclerosis (SSc) is associated with widespread microangiopathy. Prominent clinical manifestations include nailfold capillary alterations, obliterative small vessel vascular changes in the pulmonary, renal, and myocardial circulations, and cutaneous telangiectasia [1]. The pathogenesis of vascular damage in SSc is poorly understood, effective treatments are lacking, and the process is associated with tremendous morbidity and mortality. A wide spectrum of gastrointestinal (GI) manifestations occurs in SSc, with some form of GI involvement seen in almost 90% of patients [2]. In 1996, gastric antral vascular ectasia (GAVE) was first recognized as a complication of SSc when Watson et al. [3] described five patients with SSc who had severe transfusion-dependent anemia secondary to recurrent GI bleeding. On careful evaluation, these patients were found to have GAVE (also called “watermelon stomach”). Subsequent studies have indicated that GAVE is not uncommon in SSc, with some estimates ranging as high as 5.7 % of SSc patients developing this complication [4]. As the term “watermelon stomach” suggests, GAVE is characterized by hyperemic antral stripes seen on gastroscopy. Histopathologic examination of the lesional mucosa characteristically shows dilated capillaries, focal thrombi, and hyperplasia of the lamina propria [5]. These lesions can—and often do—bleed, leading to chronic GI bleeding and anemia. The cause of GAVE remains unclear. It has been suggested that when associated with SSc, GAVE is a manifestation of SSc microangiopathy and accompanying vascular changes are caused by activation of inflammatory cells, leading to endothelial cell damage, cytokine release, and further vascular damage [3]. Interestingly, all but one of the five SSc patients originally described by Watson et al. [1] had cutaneous telangiectasias, suggesting that antral lesions are another representation of the systemic vascular phenomena seen in SSc [3]. Because it is associated with recurrent GI bleeding, GAVE remains a significant problem in SSc. Current treatments include endoscopic laser therapy with yttrium-aluminumgarnet or argon plasma coagulation, as well as iron supplementation, proton pump inhibitors, and supportive blood transfusions.

Ataxia-telangiectasia

Classic ataxia-telangiectasia (AT) is a rare autosomal recessive disorder characterized by progressive cerebellar dysfunction leading to unsteady gait in early childhood, oculomotor apraxia, and ocular and cutaneous telangiectasias.1,2 Other neurologic features such as movement disorders, dysarthria, and peripheral neuropathy are usually present, and non-neurologic features include sinopulmonary infections, immune dysfunction, endocrine disorders, malignancies, and an increased sensitivity to ionizing radiation. AT is caused by mutations in the ataxia telangiectasia mutated (ATM) protein, which is integral to cell cycle checkpoint control and repair of double-stranded DNA breaks.3 No known treatment for AT exists. AT may infrequently present in milder “variant” forms in which the neurologic features are not as rapidly progressive1,4,5; however, the risk of malignancy is likely elevated and such patients may also be radiosensitive. In this issue of Neurology ®, Verhagen et al.6 compare the clinical and diagnostic features of 13 adults with variant AT to those of 6 patients with classic AT. While patients …

HLA-G Expression in the Skin of Patients with Systemic Sclerosis

To determine HLA-G expression in skin biopsies from patients with systemic sclerosis (SSc), and its association with epidemiological, clinical, and laboratory variables and survival. Paraffin-embedded skin biopsies obtained from 21 SSc patients (14 limited SSc, 7 diffuse SSc) and from 28 healthy controls were studied. HLA-G expression was evaluated by immunohistochemistry. HLA-G molecules were detected in 57% of skin biopsies from patients with SSc (9 from limited SSc, 3 from diffuse SSc), whereas no control sample expressed HLA-G (p=0.000004). In patients, HLA-G molecules were consistently observed within epidermal and some dermal cells. HLA-G expression was associated with a lower frequency of vascular cutaneous ulcers (p=0.0004), telangiectasias (p=0.008), and inflammatory polyarthralgia (p=0.02). After a 15-year followup, SSc patients who exhibited HLA-G survived longer than patients who did not. HLA-G is expressed in skin biopsies from patients with SSc, and this is associated with a better disease prognosis. This suggests a modulatory role of HLA-G in SSc, as observed in other skin disorders.

Comparative Efficacy of Nonpurpuragenic Pulsed Dye Laser and Intense Pulsed Light for Erythematotelangiectatic Rosacea

Erythematotelangiectatic (ET) rosacea is commonly treated with a variety of laser and light-based systems. Although many have been used successfully, there are a limited number of comparative efficacy studies. To compare nonpurpuragenic pulsed dye laser (PDL) with intense pulsed light (IPL) treatment in the ability to reduce erythema, telangiectasia, and symptoms in patients with moderate facial ET rosacea. Twenty-nine patients were enrolled in a randomized, controlled, single-blind, split-face trial with nonpurpuragenic treatment with PDL and IPL and untreated control. Three monthly treatment sessions were performed with initial PDL settings of 10-mm spot size, 7 J/cm(2), 6-ms pulse duration and cryogen cooling, and initial IPL settings of 560-nm filter, a pulse train of 2.4 and 6.0 ms in duration separated by a 15-ms delay, and a starting fluence of 25 J/cm(2). Evaluation measures included spectrophotometric erythema scores, blinded investigator grading, and patient assessment of severity and associated symptoms. PDL and IPL resulted in significant reduction in cutaneous erythema, telangiectasia, and patient-reported associated symptoms. No significant difference was noted between PDL and IPL treatment. A series of nonpurpuragenic PDL and IPL treatments in ET rosacea was performed with similar efficacy and safety, and both modalities seem to be reasonable choices for the treatment of ET rosacea.

Gastric outlet obstruction due to adenocarcinoma in a patient with Ataxia-Telangiectasia syndrome: a case report and review of the literature

BackgroundAtaxia-Telangiectasia syndrome is characterized by progressive cerebellar dysfunction, conjuctival and cutaneous telangiectasias, severe immune deficiencies, premature aging and predisposition to cancer. Clinical and radiographic evaluation for malignancy in ataxia-telangiectasia patients is usually atypical, leading to delays in diagnosis.Case presentationWe report the case of a 20 year old ataxia-telangiectasia patient with gastric adenocarcinoma that presented as complete gastric outlet obstruction.ConclusionA literature search of adenocarcinoma associated with ataxia-telangiectasia revealed 6 cases. All patients presented with non-specific gastrointestinal complaints suggestive of ulcer disease. Although there was no correlation between immunoglobulin levels and development of gastric adenocarcinoma, the presence of chronic gastritis and intestinal metaplasia seem to lead to the development of gastric adenocarcinoma. One should consider adenocarcinoma in any patient with ataxia-telangiectasia who presents with non-specific gastrointestinal complaints, since this can lead to earlier diagnosis.