Hereditary benign telangiectasia: a case report Klara Cvenkel1, Violeta Hosta1 , Mateja Starbek Zorko1,2 ✉ ¹Department of Dermatovenereology, Ljubljana University Medical Centre, Ljubljana, Slovenia. 2 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. S14 2022;31 Suppl:S14-S17 doi: 10.15570/actaapa.2022.s5 Introduction Hereditary benign telangiectasia (HBT) is an inherited dermato- sis that typically presents with telangiectasia, or dilation of blood vessels in the dermis on the skin and lips. It is an autosomal domi- nant disease that clinically manifests during childhood and does not affect any other organ (1). Typical round, oval, dendritic, or punctate telangiectasias are present, and they may be grouped or diffuse. Areas exposed to light, such as the face, the edge of the lips, the neck, and the upper part of the chest, are particularly affected (2). Skin changes are usually asymptomatic and can be- come lighter with age (3). Case report A 37-year-old woman came to the dermatology clinic due to asymptomatic red to livid spots on her skin, which first appeared on her face at age four and over the following years spread to her upper torso and right arm. At the age of eight, her mother was also treated at the dermatology clinic because of similar skin changes. At that time, extensive diagnostics were carried out, but no defini- tive diagnosis was made. In recent years, the patient has noticed a fading of skin changes, which she connects with less stress. Oth- erwise she is healthy and she is not receiving any regular therapy. In her family history, both her mother and her daughter have ex- perienced similar changes. During the examination, asymmetrically distributed livid to erythematous macules of various sizes were visible on the skin of the face, torso, and arms (Figs. 1–3). Abstract Hereditary benign telangiectasia is an autosomal dominant inherited dermatosis with typical presentation of telangiectasia of the skin and lips. The cause is still unknown. It is a primary telangiectasia that develops during childhood without systemic symptoms. Clinically round, oval, dendritic, or punctate telangiectasias are present, mostly asymptomatic, and they may cause only aesthetic problems. Because a similar clinical picture can be seen in several other skin diseases that may manifest not only with vascular lesions of the skin but also with systemic involvement and possible serious complications, we must be aware of all differential di- agnostic possibilities. We present the case of a 37-year-old patient with hereditary benign telangiectasia to emphasize the impor- tance of establishing the correct diagnosis and presenting proper information about the disease in a patient with telangiectasia of the skin. Keywords: hereditary benign telangiectasia, autosomal dominant, asymptomatic, case report Acta Dermatovenerologica Alpina, Pannonica et Adriatica Acta Dermatovenerol APA Received: 28 December 2021 | Returned for modification: 1 February 2022 | Accepted: 15 February 2022 ✉ Corresponding author: matejastarbekzorko@gmail.com Figure 1 | Livid to erythematous macules on the patient’s back. Figure 2 | Livid to erythematous macules on the patient’s chest. Figure 3 | Close-up view of the patient’s rash: multiple erythematous macules. S15 Acta Dermatovenerol APA | 2022;31 Suppl:S14-S17 Hereditary benign telangiectasia: a case report The patient had a biopsy of a change on her back, where a slightly telangiectatically dilated small blood vessel of the super- ficial plexus was visibly multiplied, without inflammation, which corresponds to the referral diagnosis of telangiectatic nevi (Fig. 4). For further diagnosis, the patient was referred to a geneticist, who examined her and gave the opinion that genetic testing was not necessary because this type of disease is a mosaic disorder, and possible genetic defects should be looked for in skin changes, which means a repeated biopsy of the skin: both affected and un- affected skin. Because this type of diagnosis was not absolutely necessary, we did not choose it. Self-monitoring of changes and appropriate skin protection are advised. Discussion Telangiectasias are irregular dilations of the final vessels of the subpapillary plexus in the superficial dermis (4). They can be seen in systemic diseases such as dermatomyositis, lupus erythemato- sus, scleroderma, or cirrhosis, or in pregnancy, but they can also be related to hereditary diseases such as HBT (3). HBT was first mentioned in 1971 (5) but its etiopathogenesis remains unknown. There is some speculation about the participation of angiogenic factors, or oversensitivity to estrogen or progesterone in the affect- ed areas, but these hypotheses are still being investigated and have not been proven yet (6). On the other hand, Brancati et al. suggest that HBT and capillary malformations may both be part of the wide phenotypic spectrum of the same clinical entity and, according to their study, narrowing of the CMC1 locus is a significant step to- ward identification of the gene that is causing disease (3). HBT is typically observed in several family members, is inherited in an autosomal dominant manner, and is more common in women (7). Characteristic skin changes usually occur in childhood, but cases of neonatal occurrence have also been described (6). The disease typically presents with round, oval, dendritic, or punctate telangiectasias arranged in groups or diffuse (6). Areas exposed to light (the face, neck, and upper part of chest) are particularly af- fected (5). Skin changes are asymptomatic and remain stable for a long time. The condition presents only aesthetic problems without affecting the patients’ health (2). The appearance may change over time. Aging skin can mask telangiectasias. In the early stages, the changes are small and red, increasing and becoming lighter with age (6). Bleeding diathesis and systemic vascular lesions are ab- sent, and HBT is not associated with systemic involvement (8). The diagnosis is usually made based on a typical clinical pic- ture, family history, and the absence of mucosal involvement or certain other diseases (most often hematological), in which similar changes in the skin may occur. The typical clinical features of HBT, which help establish the correct diagnosis, are: 1) punctate, dendritic, round, or oval ery- thematous macules accompanied by telangiectasias; 2) changes appearing on the skin, whereas the mucosa is not affected; 3) no tendency to bleed (e.g., epistaxis or gastrointestinal bleeding) and unrelated to systemic diseases; 4) telangiectasias usually occur af- ter birth and before puberty; 5) autosomal dominant inheritance; and 6) in histology, expansion of the venous plexus into the super- ficial dermis is characteristic (9). The histology of HBT shows normal epidermis and dilated ven- ules as well as capillaries and arterioles in the upper dermis (4). The clinical picture in patients with HBT can be misleading or sim- ilar to a wide variety of diseases, including serious diseases with associated complications that require treatment, and so it is neces- sary to carefully check the history of this patient and bear in mind other possible diseases that manifest with telangiectasia. In such cases, appropriate additional diagnostics should be performed to establish the correct diagnosis. Some elements of differential diag- nosis are summarized in Table 1. In a patient with telangiectasia, capillary malformation–arteriovenous malformation (CM-AVM) syndrome, hereditary hemorrhagic telangiectasia (HHT), acquired port-wine stain, unilateral nevoid telangiectasia, generalized es- sential telangiectasia, spider angiomas, and telangiectasia macu- laris eruptiva perstans (TMEP) should be considered in differential diagnosis in addition to HBT. CM-AVM syndrome is a rare genetic disease that affects blood vessels. In CM-AVM, capillaries are dilated and blood flow is in- creased in the surface of the skin. Dilated capillaries often appear as round, small, pink to red spots on the skin of the face and upper and lower extremities. There may also be abnormal connections between blood vessels, such as in AVM. Skin changes can occur very early, at birth, or develop later in childhood. More serious vascular abnormalities can also occur, affecting the skin, muscles, bones, spine, brain, and heart. This can cause serious problems, such as bleeding, epileptic seizures, migraines, and heart failure. Most people with AVM are asymptomatic and have no problems, and so sometimes AVM is found only after death, during autopsy (10). HHT or Osler–Weber–Rendu syndrome is an autosomal domi- nant disease. Clinically, HHT is represented by telangiectasias manifesting as macules and papules, with a pinhead size up to a few millimeters, spotted, and sometimes with linear or spider-like changes (11). They are often found on the face, nasal and oral mu- cosa, lips, tongue, ears, arms, legs, and chest, but they can also be found in internal organs such as the lungs, liver, gastrointestinal tract, genitourinary tract, and elsewhere (12). Recurrent epistaxis is most typical for this condition and begins in early childhood or adolescence. Bleeding can also manifest itself in the form of he- maturia or intestinal bleeding, and very rarely as skin bleeding. There is no causal treatment, and most patients are only treated with support. Vascular abnormalities can be treated surgically and by embolization, and nosebleeds by laser. With frequent bleeding, many patients need long-term treatment with iron supplements. Some patients need injections of parenteral iron supplements. Drugs that inhibit fibrinolysis, such as aminocaproic acid, may be effective (13). Generalized essential telangiectasia is a rare condition that usu- ally occurs in women age 40 to 50, but it can also occur in child- hood. It occurs clinically as areas of telangiectasia that initially Figure 4 | Histopathological appearance of the patient’s punch biopsy. S16 Acta Dermatovenerol APA | 2022;31 Suppl:S14-S17K. Cvenkel et al. appear on the legs and slowly spread to the trunk and arms. Numb- ness, tingling, a burning sensation in the extremities, and ocular manifestations such as conjunctival telangiectasia have also been reported (14). Bleeding on the skin and mucous membranes is not a typical feature of the disease, although it is mentioned by many authors (15). Generalized essential telangiectasias are very difficult to remove. Patients can use concealer cosmetics or self-tanning lo- tions to hide telangiectasias. There is usually no response to scle- rotherapy. Recently, various promising vascular lasers (Nd-YAG) have been shown to treat generalized essential telangiectasia (16). Acquired port-wine stain is a rare condition that occurs in early childhood. Acquired port-wine stain is often seen after lo- cal trauma. It can also appear in pregnancy or when taking oral contraceptives with additional estrogen. Acquired port-wine stain manifests as erythematous macules with small or no telangiecta- sias unilaterally on the surface of the face and neck (6). Unilateral nevoid telangiectasia may be congenital or acquired in life periods with high estrogen levels (e.g., puberty and preg- nancy). The changes occur in photoexposed areas of the skin, and the disease is limited to the skin and has no systemic involvement (6). The treatment is a cosmetic overlay. The use of a suitable laser is an alternative to aesthetic improvement (17). Spider angiomas are common in children and adults, affecting 10 to 15% of the population. Solitary angiomas are benign, but they can also be markers for systemic diseases. They are usually found in patients with liver disease or pregnant women with spi- der nevus characteristics and radial capillary expansion (6). TMEP is a form of cutaneous mastocytosis that is usually seen in the middle-aged population and is rarely found in childhood. Clinically, it manifests as erythematous or pigmented macules and papules with telangiectasias on the trunk, arms, and legs. To- luidine blue histopathology exposes a slightly increased number of mast cells located around dilated blood vessels (6). Treatment of TMEP is adjusted based on clinical symptoms and systemic in- volvement. There are no drugs to treat TMEP, and so it is very im- portant to identify and avoid factors that promote mast cell break- down (sunlight exposure, high temperatures, alcohol, and drugs). Pruritus and urticaria can be managed with H1 antagonists. Skin lesions and symptoms can be improved by psoralen plus ultravio- let light A, which inhibits histamine release from mast cells. How- ever, there may be recurrence after treatment ends. Intense light pulsing with a wavelength of 585 nm was shown to be effective in two cases described in the literature, but recurrence occurred after 14 months of therapy. Ketotifen, doxepin, cromolyn sodium, local and systemic corticosteroids, leukotriene antagonists, inter- feron alpha, and electron beam radiation have also been reported as therapies (18). HBT skin lesions are asymptomatic and usually only aestheti- cally disturbing. It is not possible to prevent their changes. Be- cause the changes are benign, treatment is not necessary, and the changes may only be observed. If removal is desired, appropriate laser treatment is the treatment of choice (8). Conclusions HBT is an autosomal dominant skin disease with typical presen- tation of round, oval, dendritic, or punctate telangiectasias. It is more common in women, and areas exposed to light are mostly affected. Skin changes in HBT are asymptomatic and cause mostly aesthetic problems. However, when treating patients with tel- angiectasias, we must be aware of serious and potentially life- threatening diseases that can also be hidden behind the innocent clinical picture of telangiectasias. Because it is clinically difficult to distinguish between such diseases, it is very important to be familiar with all the differential diagnostic options, carefully ex- amine the patient, take a good medical history, and possibly per- form additional tests. Doing so ensures that we will treat patients correctly, make the proper diagnosis, explain the nature of the disease, and even refer them to other specialists that can explain possible complications of the disease and all treatment options. Table 1 | Differential diagnoses for telangiectasias. Disease Gene/defect Age of patients Systemicinvolvement Mucous membrane involvement Need for referral Hereditary benign telangiectasia No Rarely at birth, mostly in early childhood No No No Capillary malformation– arteriovenous malformation syndrome RASA1 gene at 5q13.3, encodes protein RAS21 At birth or later in childhood Yes Yes Yes Hereditary hemorrhagic telangiectasia ACVRL ENG GDF2 SMAD Average at age 12 Yes Yes Yes Generalized essential telangiectasia No Average at age 40–50 No Yes No Acquired port-wine stain No After local trauma, pregnancy No No No Unilateral nevoid telangiectasia No Congenital, puberty, pregnancy, high estrogen levels No No No Spider angiomas No Pregnancy, middle age Yes No Yes if liver/thyroid disease suspected Telangiectasia macularis eruptiva perstans No Middle age Yes No Yes Unilateral nevoid telangiectasia No Congenital, puberty, pregnancy, high estrogen levels No No No S17 Acta Dermatovenerol APA | 2022;31 Suppl:S14-S17 Hereditary benign telangiectasia: a case report References 1. 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