The Journal of Dermatology Vol. 19: 384-386, 1992
Hereditary Benign Telangiectasia: Two Case Reports Douglas Puppin Jr., Michel Rybojad and Patrice Morel Abstract
We present two cases of hereditary benign telangiectasia (HBT) in which the genetic findings are compatible with an autosomal dominant hypothesis. The lesions persisted indefinitely for many years without effect on the general health of the patients. The term hereditary benign telangiectasia distinguishes the disorder from the more serious hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber). The etiology remains unknown. The condition causes only cosmetic disability and is not associated with any other diseases.
Key words:
skin involvement; telangiectasias; autosomal dominant inheritance; review
Introduction
Case Reports
Ryan and Wells (1) first coined the term "hereditary benign telangiectasia" (HBT) as a new clinical entity in 1971. They reported seven children affected with HBT and described some characteristic features of this disease: 1) Telangiectasia is seen before adolescence, but is not present in the first year of life. 2) Lesions may be punctate, linear, plaquelike, arborizing, spider or white halo. 3) The lesions are more prominent during pregnancy. 4) There is an absence of notable associated diseases. 5) There is a simple distension of the horizontal subpapillary vessels. 6) Inheritance of the trait is likely to be autosomally dominant We present here two cases with familial features [the first case was previously reported (2)] and discuss the relevant literature.
Case 1 An eight-year-old girl presented in 1986with scattered telangiectasias over the face. She was clinically well and laboratory analysis was unremarkable. After six-years of follow up, she presented with multiple mottled erythematous patches situated principally over the face, neck, and anterior chest of three distinct types: a plaque lesion, a spider lesion, and a characteristic erythematous punctate lesion with a white vasoconstricted halo (Fig. 1). They had enlarged in size in accordance with her growth. Clinical and laboratory examinations were unremarkable, and there was no history of epistasix or hemorrhagic episodes. Her paternal grandmother and uncles demonstrated only a few telangiectatic vessels over the face. Her brother had a few telangiectatic vessels disseminated over the body, and her mother had facial telangiectasias and a round patch over the neck (Fig. 2). Laboratory and clinical findings were normal in all family members. Histological sections obtained from the patient's telangiectatic lesion showed dilated capillaries and venules in the upper dermis. Case 2 A fifteen-year-old boy presented in 1990 with a round telangiectatic patch on the neck (Fig. 3). He recounted no changes either in color or in number, but the size had enlarged in accordance with his growth.
Received December 17, 1990; accepted for publication March 2,1992. Department of Dermatology, Hopital Saint-Louis-Paris VII University, Paris, France. Reprint requests to: Douglas Puppin Jr., M.D., Department of Dennatology-Dennatopathology Section, Hopital Cantonal Universitaire de Geneve, 24, rue Micheli-duCrest, 1211-Geneve 4, Switzerland.
Hereditary Benign Telangiectasia
Fig. 1. Characteristic erythematous punctate lesion with a white vasocontricted halo.
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Fig. 2. Facial telangiectasias and a round patch over the neck.
His father had two erythematous macules 13 x 15 mm in size on the neck. His brother also had erythematous patches on the right arm. The patient's lesions were noted at the age of 8 years. All family members studied were healthy, and laboratory findings were normal. Other members in the pedigree did not have telangiectasias. Histopathologically, the lesions showed dilated capillaries and venules in the upper dermis.
Discussion HBT in children is a rare entity and has been published under various names (1-5). The lesions in children usually begin over the face and later involve the hands and wrists. The literature suggests that HBT is inherited in an autosomally dominant fashion (1-6), as are our cases. Hereditary hemorrhagic telangiectasia (HHT) (Rendu-Osler-Weber), which is also inherited in an autosomally dominant pattern, must be distinguished from HBT because of the presence of mucous lesions and recurrent epistaxis. However, a form of HHT with only late hemorrhagic manifestations has been published (7). Telangiectasia is also the diagnostic cutaneous sign of the Louis-Bar syndrome or ataxia telangiectasia, which appears with cerebellar ataxia in children. Fine, wiry, elongated vessels are found on the conjunctivae (8). The lesions of nevoid unilateral telangiectasia are almost strictly unilateral, and the telangiectatic vessels are almost exclusively
Fig. 3. Round telangiectatic patch on the neck.
localized over the neck and the upper extremities, with a predominance in pregnant females (9). Generalized essential telangiectasia is much more common among adult women without family history. It occurs most frequently on the lower extremities and tends to extend progressively (8-12). The pathogenesis ofHBT remains unknown. Many etiologies have been discussed for
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telangiectasia. During pregnancy, many factors are present that stimulate angiogenesis in the growing fetus and participate in the growth of the placenta (13). It is possible that one ofthese factors stimulates the growth of telangiectasias in children. Because some vascu\ar telangiectasias are associated with high levels of circulating estrogen, Sadick (14) studied thirteen female patients with telangiectasias on the lower extremities. Contrary to expected results, they were unable to demonstrate the presence of estrogen or progesterone receptors in their telangiectasias using immunocytochemical techniques. If estrogen does not act directly, it may act indirectly by stimulating another angiogenic factor such as platelet-derived endothelial cell growth factor (PD-ECGF) (15), fibroblast growth factor (FGF), or transforming growth factor beta (TGF-b or angiogenin), which in turn mediates the formation of the telangiectasia (16,17). Smoller and Rosen (18) found decreased nerve fibers in histological sections of lesions from patients with congenital telangiectasias and postulated that these vascular ectasias may be related to an abnormality in the innervation of blood vessels, with a lack of neural modulation causing decreased vessel tone and subsequent progressive vascular dilation. Such a mechanism may apply to our patients; however, we did not investigate the number of nerves present in our biopsy specimens. The role of these mechanisms in HBT needs to be further clarified. Acknowledgment Dr. Douglas Ing reviewed the manuscript; his help is gratefully acknowledged.
References I) Ryan 1), Wells RS: Hereditary benign telangiectasia, Trans St]ohns Hosp Dermatol Soc, 57: 148-156,1971.
2) Ghnassia M, Abirached G, Morel P: Telangiectasies essentielles de l'enfant: Une observation familiale, Ann Dermatol Venereol, 114: 1389-1391,1987. 3) Gelmetti C, Ermacora C: Hereditary benign telangiectasia, in: 17th World Congress of Dermatology; Part 11,1987, P 517. 4) Wells RS: Hereditary benign telangiectasia, Br ] Dermatol, 184: 93-94, 1971. 5) Gold MH, Eramo 1.., Prendiville jS: Hereditary benign telangiectasia, Pediatr Dermatol, 6: 194-197,1989. 6) Watanabe M, Tomita Y, Tagami H: Hereditary benign telangiectasia: A congenital type, Dmnatologica, 181: 152-153, 1990. 7) Bazexj, Peyrotj, Samalens G, Ferrier j, LouvetjP, Basex A: Telangiectasies generalisees, alopecie, syndrome malformatif, Ann Dermatol Venereol, 10: 795-800, 1979. 8) Kitchen CS, Lottenberg R: Chronic painless hematuria and urethral bleeding as the presenting manifestations of Osler-Weber-Rendu disease,] Urol, 116: 681-682, 1976. 9) Mellor A: Hereditary hemorrhagic telangiectasia, Br] Clin Praa, 37: 234-236, 1983. 10) Kint A, Geerts ML, Platevoet D: Generalized essential telangiectasia, Arch &lg Dermatol Syph, 28: 377-385, 1972. 11) Gropper C, Bermejo D, Bouyx P, Belperron P, Verrey jL, Schnitzler L: Telangectasies stellaires naevoides unilaterales acquises ou congenitales, A propos de 5 cas, Ann Dermatol Venereol, 28: 377-385, 1978. 12) Becker SW: Generalized telangiectasia, ArchDermatol Syph, 14: 387-426, 1926. 13) McGrae jD, Winkelmann RK: Generalized essential telangiectasia. Report of a clinical and histochemical study of 13 patients with acquired cutaneous lesions, ] Am Med Assoc, 185: 909-913, 1963. 14) Sadick NS, Niedt GW: A study of estrogen and progesterone receptors in spider telangiectasias of the lower extremities, ] Dermatol Surg Oncol; 16: 620-623, 1990. 15) Miyazono K, Okabe T, Urabe A, Takaku F, Heldin CH: Purification and properties of an endothelial cell growth factor from human platelets,] Bioi Chern, 262: 4098-4103, 1987. 16) Mullane Dj: Varicose veins of pregnancy, Am] Obstet GyneaJI, 90: 780-788, 1964. 17) Folkman j: Successful treatment of an angiogenic disease, N Eng] Med, 320: 1211-1213, 1989. 18) Smoller BR, Rosen S: Port-wine stains: A disease of altered neural modulation of blood vessels?, Arch Dermatol, 122: 177-179,1986.
Hereditary Benign Telangiectasia: Two Case Reports Douglas Puppin Jr., Michel Rybojad and Patrice Morel Abstract
We present two cases of hereditary benign telangiectasia (HBT) in which the genetic findings are compatible with an autosomal dominant hypothesis. The lesions persisted indefinitely for many years without effect on the general health of the patients. The term hereditary benign telangiectasia distinguishes the disorder from the more serious hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber). The etiology remains unknown. The condition causes only cosmetic disability and is not associated with any other diseases.
Key words:
skin involvement; telangiectasias; autosomal dominant inheritance; review
Introduction
Case Reports
Ryan and Wells (1) first coined the term "hereditary benign telangiectasia" (HBT) as a new clinical entity in 1971. They reported seven children affected with HBT and described some characteristic features of this disease: 1) Telangiectasia is seen before adolescence, but is not present in the first year of life. 2) Lesions may be punctate, linear, plaquelike, arborizing, spider or white halo. 3) The lesions are more prominent during pregnancy. 4) There is an absence of notable associated diseases. 5) There is a simple distension of the horizontal subpapillary vessels. 6) Inheritance of the trait is likely to be autosomally dominant We present here two cases with familial features [the first case was previously reported (2)] and discuss the relevant literature.
Case 1 An eight-year-old girl presented in 1986with scattered telangiectasias over the face. She was clinically well and laboratory analysis was unremarkable. After six-years of follow up, she presented with multiple mottled erythematous patches situated principally over the face, neck, and anterior chest of three distinct types: a plaque lesion, a spider lesion, and a characteristic erythematous punctate lesion with a white vasoconstricted halo (Fig. 1). They had enlarged in size in accordance with her growth. Clinical and laboratory examinations were unremarkable, and there was no history of epistasix or hemorrhagic episodes. Her paternal grandmother and uncles demonstrated only a few telangiectatic vessels over the face. Her brother had a few telangiectatic vessels disseminated over the body, and her mother had facial telangiectasias and a round patch over the neck (Fig. 2). Laboratory and clinical findings were normal in all family members. Histological sections obtained from the patient's telangiectatic lesion showed dilated capillaries and venules in the upper dermis. Case 2 A fifteen-year-old boy presented in 1990 with a round telangiectatic patch on the neck (Fig. 3). He recounted no changes either in color or in number, but the size had enlarged in accordance with his growth.
Received December 17, 1990; accepted for publication March 2,1992. Department of Dermatology, Hopital Saint-Louis-Paris VII University, Paris, France. Reprint requests to: Douglas Puppin Jr., M.D., Department of Dennatology-Dennatopathology Section, Hopital Cantonal Universitaire de Geneve, 24, rue Micheli-duCrest, 1211-Geneve 4, Switzerland.
Hereditary Benign Telangiectasia
Fig. 1. Characteristic erythematous punctate lesion with a white vasocontricted halo.
385
Fig. 2. Facial telangiectasias and a round patch over the neck.
His father had two erythematous macules 13 x 15 mm in size on the neck. His brother also had erythematous patches on the right arm. The patient's lesions were noted at the age of 8 years. All family members studied were healthy, and laboratory findings were normal. Other members in the pedigree did not have telangiectasias. Histopathologically, the lesions showed dilated capillaries and venules in the upper dermis.
Discussion HBT in children is a rare entity and has been published under various names (1-5). The lesions in children usually begin over the face and later involve the hands and wrists. The literature suggests that HBT is inherited in an autosomally dominant fashion (1-6), as are our cases. Hereditary hemorrhagic telangiectasia (HHT) (Rendu-Osler-Weber), which is also inherited in an autosomally dominant pattern, must be distinguished from HBT because of the presence of mucous lesions and recurrent epistaxis. However, a form of HHT with only late hemorrhagic manifestations has been published (7). Telangiectasia is also the diagnostic cutaneous sign of the Louis-Bar syndrome or ataxia telangiectasia, which appears with cerebellar ataxia in children. Fine, wiry, elongated vessels are found on the conjunctivae (8). The lesions of nevoid unilateral telangiectasia are almost strictly unilateral, and the telangiectatic vessels are almost exclusively
Fig. 3. Round telangiectatic patch on the neck.
localized over the neck and the upper extremities, with a predominance in pregnant females (9). Generalized essential telangiectasia is much more common among adult women without family history. It occurs most frequently on the lower extremities and tends to extend progressively (8-12). The pathogenesis ofHBT remains unknown. Many etiologies have been discussed for
386
PuppinJr et al
telangiectasia. During pregnancy, many factors are present that stimulate angiogenesis in the growing fetus and participate in the growth of the placenta (13). It is possible that one ofthese factors stimulates the growth of telangiectasias in children. Because some vascu\ar telangiectasias are associated with high levels of circulating estrogen, Sadick (14) studied thirteen female patients with telangiectasias on the lower extremities. Contrary to expected results, they were unable to demonstrate the presence of estrogen or progesterone receptors in their telangiectasias using immunocytochemical techniques. If estrogen does not act directly, it may act indirectly by stimulating another angiogenic factor such as platelet-derived endothelial cell growth factor (PD-ECGF) (15), fibroblast growth factor (FGF), or transforming growth factor beta (TGF-b or angiogenin), which in turn mediates the formation of the telangiectasia (16,17). Smoller and Rosen (18) found decreased nerve fibers in histological sections of lesions from patients with congenital telangiectasias and postulated that these vascular ectasias may be related to an abnormality in the innervation of blood vessels, with a lack of neural modulation causing decreased vessel tone and subsequent progressive vascular dilation. Such a mechanism may apply to our patients; however, we did not investigate the number of nerves present in our biopsy specimens. The role of these mechanisms in HBT needs to be further clarified. Acknowledgment Dr. Douglas Ing reviewed the manuscript; his help is gratefully acknowledged.
References I) Ryan 1), Wells RS: Hereditary benign telangiectasia, Trans St]ohns Hosp Dermatol Soc, 57: 148-156,1971.
2) Ghnassia M, Abirached G, Morel P: Telangiectasies essentielles de l'enfant: Une observation familiale, Ann Dermatol Venereol, 114: 1389-1391,1987. 3) Gelmetti C, Ermacora C: Hereditary benign telangiectasia, in: 17th World Congress of Dermatology; Part 11,1987, P 517. 4) Wells RS: Hereditary benign telangiectasia, Br ] Dermatol, 184: 93-94, 1971. 5) Gold MH, Eramo 1.., Prendiville jS: Hereditary benign telangiectasia, Pediatr Dermatol, 6: 194-197,1989. 6) Watanabe M, Tomita Y, Tagami H: Hereditary benign telangiectasia: A congenital type, Dmnatologica, 181: 152-153, 1990. 7) Bazexj, Peyrotj, Samalens G, Ferrier j, LouvetjP, Basex A: Telangiectasies generalisees, alopecie, syndrome malformatif, Ann Dermatol Venereol, 10: 795-800, 1979. 8) Kitchen CS, Lottenberg R: Chronic painless hematuria and urethral bleeding as the presenting manifestations of Osler-Weber-Rendu disease,] Urol, 116: 681-682, 1976. 9) Mellor A: Hereditary hemorrhagic telangiectasia, Br] Clin Praa, 37: 234-236, 1983. 10) Kint A, Geerts ML, Platevoet D: Generalized essential telangiectasia, Arch &lg Dermatol Syph, 28: 377-385, 1972. 11) Gropper C, Bermejo D, Bouyx P, Belperron P, Verrey jL, Schnitzler L: Telangectasies stellaires naevoides unilaterales acquises ou congenitales, A propos de 5 cas, Ann Dermatol Venereol, 28: 377-385, 1978. 12) Becker SW: Generalized telangiectasia, ArchDermatol Syph, 14: 387-426, 1926. 13) McGrae jD, Winkelmann RK: Generalized essential telangiectasia. Report of a clinical and histochemical study of 13 patients with acquired cutaneous lesions, ] Am Med Assoc, 185: 909-913, 1963. 14) Sadick NS, Niedt GW: A study of estrogen and progesterone receptors in spider telangiectasias of the lower extremities, ] Dermatol Surg Oncol; 16: 620-623, 1990. 15) Miyazono K, Okabe T, Urabe A, Takaku F, Heldin CH: Purification and properties of an endothelial cell growth factor from human platelets,] Bioi Chern, 262: 4098-4103, 1987. 16) Mullane Dj: Varicose veins of pregnancy, Am] Obstet GyneaJI, 90: 780-788, 1964. 17) Folkman j: Successful treatment of an angiogenic disease, N Eng] Med, 320: 1211-1213, 1989. 18) Smoller BR, Rosen S: Port-wine stains: A disease of altered neural modulation of blood vessels?, Arch Dermatol, 122: 177-179,1986.
