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Bilateral nevoid telangiectasia syndrome
Bilateral nevoid telangiectasia syndrome Shou-jiang Tang, MD, Marie E. Faughnan, MD MSc, Norman E. Marcon, MD
Unilateral nevoid telangiectasia syndrome (UNTS) typically is associated with elevated estrogen levels in various physiologic and pathologic conditions, such as pregnancy, puberty, hormonal replacement therapy, hepatic cirrhosis, and liver disease.1-11 Unilateral cutaneous telangiectasias usually develop in the C3 to T3 dermatomal distribution. Fewer than 70 cases of UNTS are reported in dermatologic publications. Reported here is the first case of bilateral nevoid telangiectasia syndrome (BNTS). In addition, our patient, who was pregnant, had numerous reversible telangiectasias in the GI tract, which regressed completely after delivery. CASE REPORT A previously healthy 33-year-old Chinese woman at 23 weeks’ gestation developed a progressive bilateral ‘‘rash’’ over the upper extremities and upper abdomen. Three to 4 weeks later, she presented with pruritus related to the ‘‘rash,’’ progressive weakness, and dyspnea. There was no fever, chills, or other systemic symptom. The Hb level had decreased from 14.6 g/dL (normal: 14.0-18.0 g/dL) at a prenatal visit to 6.1 g/dL on presentation to the emergency room of another hospital. Five units of packed red blood cells were transfused. There was recent melena that the patient had mistakenly attributed to the prenatal oral iron supplement. She was not taking any herbal medication or non-steroidal anti-inflammatory drug. There was no history of recurrent epistaxis, previous GI bleeding, anemia, or liver disease. She was Gravida 2, Para 1, having delivered a healthy baby girl 3 years earlier. During the first pregnancy, the patient had noted a similar ‘‘rash’’ of lesser severity over the upper abdomen during late pregnancy. There was no family history of liver disease, GI disease, or hereditary hemorrhagic telangiectasia (HHT). On examination, blood pressure was 113/63 mm Hg and body temperature was normal. There were hundreds of ‘‘spider’’ telangiectasias on the neck, upper chest, bilateral shoulders, upper extremities, and upper abdomen in C3-T3 and T10-T11 dermatomal distributions with symmetry
Current affiliations: Center for Therapeutic Endoscopy and Endoscopic Oncology, Division of Respiratory Medicine, Department of Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada. Reprint requests: Norman E. Marcon, MD, Center for Therapeutic Endoscopy and Endoscopic Oncology, Victoria Wing 16-062, St. Michael’s Hospital, Toronto, Ontario, Canada M5B 1W8. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)01734-1 468
GASTROINTESTINAL ENDOSCOPY
Figure 1. A, ‘‘Spider’’ telangiectasias on neck, upper chest, bilateral shoulders, and upper extremities distributed symmetrically in C3 to T3 dermatomes. B, Close view of vascular lesions, which blanch with pressure. (Fig. 1). These vascular lesions blanched with pressure. There were a few small telangiectasias on the lower lip and gum, but no telangiectasia was found on the buccal mucosa. Except for the telangiectasias, there were no stigmata of chronic liver disease. Chest and precordial examinations were normal. Abdominal and obstetric examinations were appropriate for gestational age. Laboratory test results included normal leukocyte and platelet counts. Tests of liver, renal, and thyroid function were within normal ranges. There was no evidence of intra- or extravascular hemolysis: the peripheral blood smear, serum haptoglobin level, and direct and indirect Coombs’ tests were normal. The serum ferritin level was less than 6 lg/L (12-192 lg/L); iron saturation was 4% (0.20-0.50%). Serologic tests for hepatitis B and C, HIV antibody, and antinuclear antibody were negative. The serum compliment levels and coagulation profile also were within normal limits. At EGD, the entire stomach was studded with non-bleeding telangiectasias. A lung ventilation/perfusion scan and duplex US study of the lower extremities were negative for thromboembolic disease. With a tentative diagnosis of HHT, the patient then was transferred to our institution for further management. EGD was repeated and again revealed studding of the entire gastric and duodenal mucosa with angioectasias, many of which were oozing blood (Fig. 2). The surrounding mucosa appeared normal and was not friable. There were no esophageal varices or evidence of portal hypertensive gastropathy (PHG). Push enteroscopy and colonoscopy were not performed because of the late stage pregnancy and VOLUME 60, NO. 3, 2004
Bilateral nevoid telangiectasia syndrome
the diagnostic findings on EGD. Endoscopic therapy was not attempted because of the diffuse nature of the angioectasias, presumed involvement of the more distal small bowel, and the probable etiologic relationship between the findings and the elevated estrogen state during pregnancy. Treatment was supportive with reference to the GI bleeding. The plasma estradiol level was greater than 1835 pmol/L (basal level in women, 70-220 pmol/L), and progesterone level 1240 nmol/L (normal value during luteal phase, 6-64 nmol/L; during follicular phase, <6 nmol/L). The hospital course was later complicated by high output cardiac failure. The patient complained of significant dyspnea (blood oxygen saturation 90%). As part of the evaluation for HHT, cardiac US with bubble contrast study suggested mild intrapulmonary shunting; valvular regurgitation and vegetation were not noted. Pulmonary angiography failed to demonstrate any pulmonary arteriovenous malformation. Mesenteric Doppler US disclosed no evidence of intrahepatic shunting. The dyspnea was attributed to congestive heart failure caused by fluid overload, a high cardiac output state related pregnancy, GI bleeding, and blood transfusion. Subacute infectious endocarditis with leukocytosis and abnormal tests of liver function developed 3 weeks after admission. Laboratory data were the following: leukocyte count, 10.73 3 109/L (3.0-10.0 3 109/L); platelet count, 236 3 103/cm (140-440 3 103/cm); total bilirubin, 0.2 mg/dL (0.3-1.2 mg/dL); alkaline phosphatase, 89 U/L (35110 U/L); alanine aminotransferase, 60 U/L (5-40 U/L); aspartate aminotransferase, 70 U/L (5-40 U/L); serum albumin, 2.3 g/dL (3.7-4.8 g/dL); and international normalized ratio, 1.0. Blood cultures grew Streptococcus milleri that was sensitive to penicillin. The first EGD had been performed without prophylactic administration of antibiotics. Echocardiography demonstrated severe aortic regurgitation with possible valvular vegetations. Urgent cesarean section was carried out (30 weeks’ gestation). The aortic valve was successfully replaced 1 month after delivery. Histopathologic examination of the resection specimen revealed a congenital bicuspid aortic valve. The eruptive cutaneous telangiectasias resolved completely within 3 weeks after delivery. At EGD 10 weeks after delivery, all previously noted duodenal lesions had completely disappeared and only residual spots of brownish pigmentation were present in the stomach (Fig. 3). The plasma estradiol and progesterone levels had returned within normal limits. EGD at 10 months after delivery revealed fewer and fainter residual pigmentation spots in the stomach. Targeted biopsy specimens of these spots demonstrated only normal gastric mucosa without evidence of angioectasia; Helicobacter pylori were not seen. The final diagnosis was BNTS associated with pregnancy. Mother and baby are doing well.
DISCUSSION 1
Selmanowitz first suggested the term UNTS in 1970.6 To date, less than 70 cases of UNTS have been VOLUME 60, NO. 3, 2004
S-j Tang, M Faughnan, N Marcon
Figure 2. A, Endoscopic view showing numerous ‘‘spider’’ angioectasias, many oozing blood, in fundus of stomach. B, Endoscopic view of ‘‘spider’’ angioectasias in antrum.
reported in dermatologic publications. Only a few congenital cases have been published, and UNTS is not considered a familial disease.6 In general, cutaneous telangiectasias develop unilaterally in the C3 to T3 dermatomal distributions. There are cases of UNTS in which the lower thoracic dermatomes were involved. A review of 44 cases found right and left side involvement in 26 and 18 cases, respectively.6 It has been suggested that the unilateral dermatomal distribution of the telangiectasias relates to a congenitally fixed distribution of target end organs or tissues because of cutaneous morphogenesis patterns sensitive to estrogen.6,7 In some reported cases, skin biopsy specimens of the affected and of unaffected areas were obtained for estrogen and progesterone receptor assay.7,9,11 However, it is difficult to interpret the results, because of the sensitivity of the assays and the low level of estrogen receptor expression in normal skin.8 The telangiectasia in UNTS can be spider, linear, and wiry in GASTROINTESTINAL ENDOSCOPY
469
S-j Tang, M Faughnan, N Marcon
Figure 3. A, Endoscopic view at 10 weeks after delivery, showing numerous residual pigmented spots in gastric antrum. B, Close view of residual pigmented spots.
shape. On microscopic examination, dilated vessels are located in the middle to upper dermis without apparent endothelial proliferation.2,4,5 Patients with nevoid telangiectasia syndrome generally are asymptomatic or only have symptoms associated with a disease or physiologic state, such as hepatic cirrhosis and pregnancy. In addition, laboratory tests are within the normal limits in nevoid telangiectasia syndrome. As in the present case, the most common condition associated with UNTS is pregnancy.6 During normal pregnancy, maternal plasma levels of estrogen rise until term, reaching a mean level of 58,736 pmol/L (normal basal level in women: 20-60 pmol/L). In patients with UNTS, the telangiectasias usually resolve within 4 to 8 weeks after delivery. If it develops during pregnancy, UNTS is reversible but can recur in the same dermatomal distribution with subsequent pregnancies.6 Our patient apparently developed similar lesions during her first pregnancy. 470
GASTROINTESTINAL ENDOSCOPY
Bilateral nevoid telangiectasia syndrome
The greater severity and the widened distribution of the cutaneous lesions during the second pregnancy suggest increased target tissue sensitivity to estrogen after the first pregnancy. Wilkin et al.6 described several patients with UNTS who developed cutaneous telangiectasias with consecutive pregnancies, with resolution between pregnancies. Pregnancy also is associated with occasional sporadic cutaneous telangiectasias in a non-dermatomal distribution. This condition is common and has no clinical significance. Several aspects of the present case are similar to UNTS: the typical dermatomal distribution of the telangiectasias, the temporal and the probable etiologic relationship with elevated estrogen state, normal laboratory tests, and recurrence of skin lesions during the second pregnancy. However, it also differs from UNTS in two ways: the bilateral distribution and the GI-tract involvement. To our knowledge, this is the first case of BNTS in which GI involvement was documented. However, it is not known whether the GI involvement is unique to BNTS or if occult GI involvement occurs in UNTS. The differential diagnosis of nevoid telangiectasia syndrome includes HHT and generalized essential telangiectasia (GET). HHT is an inherited (autosomal dominant) disorder characterized by mucocutaneous telangiectasia and visceral involvement.12–14 Two distinct genes have been found to be the cause of HHT: endoglin mutated in HHT1 and activin receptor-like kinase 1 (ALK-1) mutated in HHT2.12 Of patients with HHT, 80% to 90% have a family history of the disorder.13 The vast majority of adult patients have recurrent spontaneous epistaxis.13 Currently, the diagnosis of HHT requires that 3 of 4 criteria be met: epistaxis, mucocutaneous telangiectasia, family history, and well-documented visceral involvement.14 The typical telangiectasias in HHT are punctiform and are most commonly found on the face, the mouth, and the hands.13 In our experience, ‘‘spider’’ telangiectasias are not commonly found in patients with HHT. In HHT, GI bleeding generally occurs until the 5th or 6th decade.12 Although the telangiectasias of HHT often become more prominent during pregnancy, they do not have a dermatomal distribution and do not resolve after delivery. In our patient, the negative family history of HHT, the absence of recurrent epistaxis, the dermatomal distribution of telangiectasias, and the resolution after delivery make HHT unlikely. In GET, the cutaneous telangiectasias are characteristically linear, mottled, or net-like. These vascular lesions appear most commonly on the lower extremities and buttocks; there is no spontaneous bleeding or visceral involvement. One reported patient with GET had GI VOLUME 60, NO. 3, 2004
Bilateral nevoid telangiectasia syndrome
bleeding caused by gastric antral vascular ectasia (GAVE).15 GET occurs most commonly in women and is likely not related to UNTS, although there is some speculation that GET may represent a generalized form of the same pathologic process as UNTS.6 Our patient had numerous GI angioectasias that regressed completely after delivery. GI involvement has not been reported in patients with UNTS without hepatic cirrhosis.6 A single case of gastric angioectasias in a patient with UNTS and hepatic cirrhosis has been reported.4 Non-bleeding angioectasias were noted in the stomach in the patient with alcoholic cirrhosis. However, portal hypertension can cause gastric varices and PHG.16,17 GAVE and gastric angioectasias can be observed in patients with cirrhosis without UNTS.18 Furthermore, in severe PHG, cherry-red spots or patches are frequently present, which mimic angioectasias. The vascular ectasia in PHG is believed to arise from the dilated mucosal and submucosal capillaries and veins.19,20 In our patient, there was no evidence of underlying liver disease or hepatic cirrhosis. Complete resolution of these lesions, as documented endoscopically, is strong evidence that these lesions were related to the elevated estrogen level during pregnancy. To our knowledge, this is the first case reported of the BNTS with GI involvement and of a nevoid telangiectasia syndrome in the absence of cirrhosis. The mucocutaneous telangiectatic lesions regressed after delivery. An elevated estrogen level can be associated with reversible angioectasia in the GI tract. Expectant supportive management until delivery is feasible and should be recommended. Antibiotics should be administered prophylactically before endoscopy if this syndrome is suspected, as well as in patients with HHT. Although endoscopic intervention is not feasible if the lesions are diffuse, endoscopy should be performed to rule out other causes of GI bleeding and to evaluate the extent of the GI angioectasias if present. Reversal of elevated estrogen status occasionally is required. REFERENCES 1. Selmanowitz VJ. Unilateral nevoid telangiectasia. Ann Intern Med 1970;73:87-90. 2. Mirrer E, Cipriano A, McGuire J. Unilateral nevoid telangiectasia. Arch Dermatol 1971;103:320-3. 3. Selmanowitz VJ. Unilateral nevoid telangiectasia. Arch Dermatol 1972;105:131.
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4. Anderton RL, Smith JG Jr. Unilateral nevoid telangiectasia with gastric involvement. Arch Dermatol 1975;111: 617-21. 5. Wilkin JK. Unilateral nevoid telangiectasia: three new cases and the role of estrogen. Arch Dermatol 1977;113:486-8. 6. Wilkin JK, Smith JG Jr, Cullison DA, Peters GE, RodriquezRigau LJ, Feucht CL. Unilateral dermatomal superficial telangiectasia. Nine new cases and a review of unilateral dermatomal superficial telangiectasia. J Am Acad Dermatol 1983;8:468-77. 7. Uhlin SR, McCarty KS Jr. Unilateral nevoid telangiectatic syndrome. The role of estrogen and progesterone receptors. Arch Dermatol 1983;119:226-8. 8. Friedman SJ, Su WP, Doyle JA. Telangiectasia. [letter] Arch Dermatol 1985;121:1484. 9. Beacham BE, Kurgansky D. Unilateral naevoid telangiectasia syndrome associated with metastatic carcinoid tumour. Br J Dermatol 1991;124:86-8. 10. Tok J, Berberian BJ, Sulica VI. Unilateral nevoid telangiectasia syndrome. Cutis 1994;53:53-4. 11. Hynes LR, Shenefelt PD. Unilateral nevoid telangiectasia: occurrence in two patients with hepatitis C. J Am Acad Dermatol 1997;36:819-22. 12. Guttmacher AE, Marchuk DA, White RI Jr. Hereditary hemorrhagic telangiectasia [review]. N Engl J Med 1995;333: 918-24. 13. Plauchu H, de Chadarevian JP, Bideau A, Robert JM. Agerelated clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet 1989;32:291-7. 14. Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000;91:66-7. 15. Checketts SR, Burton PS, Bjorkman DJ, Kadunce DP. Generalized essential telangiectasia in the presence of gastrointestinal bleeding. J Am Acad Dermatol 1997;37: 321-5. 16. Papazian A, Brailion A, Dupas JL, Sevenet F, Capron JP. Portal hypertensive gastric mucosa: an endoscopic study. Gut 1986;27:1199-203. 17. Thiruvengadam R, Gostout CJ. Congestive gastroenteropathy: an extension of nonvariceal upper gastrointestinal bleeding in portal hypertension. Gastrointest Endosc 1989; 35:504-7. 18. Sargeant IR, Loizou LA, Rampton D, Tulloch M, Bown SG. Laser ablation of upper gastrointestinal vascular ectasias: long term results. Gut 1993;34:470-5. 19. McCormack TT, Sims J, Eyre-Brook I, Kennedy H, Goepel J, Johnson AG, et al. Gastric lesions in the portal hypertension: inflammatory gastritis or congestive gastropathy. Gut 1985; 26:1226-32. 20. D’Amico G, Montalbano L, Traina M, Pisa R, Menozzi M, Spano C, et al. Natural history of congestive gastropathy in cirrhosis. The liver study group of V. Cervello hospital. Gastroenterology 1990;99:1558-64.
GASTROINTESTINAL ENDOSCOPY
471
Unilateral nevoid telangiectasia syndrome (UNTS) typically is associated with elevated estrogen levels in various physiologic and pathologic conditions, such as pregnancy, puberty, hormonal replacement therapy, hepatic cirrhosis, and liver disease.1-11 Unilateral cutaneous telangiectasias usually develop in the C3 to T3 dermatomal distribution. Fewer than 70 cases of UNTS are reported in dermatologic publications. Reported here is the first case of bilateral nevoid telangiectasia syndrome (BNTS). In addition, our patient, who was pregnant, had numerous reversible telangiectasias in the GI tract, which regressed completely after delivery. CASE REPORT A previously healthy 33-year-old Chinese woman at 23 weeks’ gestation developed a progressive bilateral ‘‘rash’’ over the upper extremities and upper abdomen. Three to 4 weeks later, she presented with pruritus related to the ‘‘rash,’’ progressive weakness, and dyspnea. There was no fever, chills, or other systemic symptom. The Hb level had decreased from 14.6 g/dL (normal: 14.0-18.0 g/dL) at a prenatal visit to 6.1 g/dL on presentation to the emergency room of another hospital. Five units of packed red blood cells were transfused. There was recent melena that the patient had mistakenly attributed to the prenatal oral iron supplement. She was not taking any herbal medication or non-steroidal anti-inflammatory drug. There was no history of recurrent epistaxis, previous GI bleeding, anemia, or liver disease. She was Gravida 2, Para 1, having delivered a healthy baby girl 3 years earlier. During the first pregnancy, the patient had noted a similar ‘‘rash’’ of lesser severity over the upper abdomen during late pregnancy. There was no family history of liver disease, GI disease, or hereditary hemorrhagic telangiectasia (HHT). On examination, blood pressure was 113/63 mm Hg and body temperature was normal. There were hundreds of ‘‘spider’’ telangiectasias on the neck, upper chest, bilateral shoulders, upper extremities, and upper abdomen in C3-T3 and T10-T11 dermatomal distributions with symmetry
Current affiliations: Center for Therapeutic Endoscopy and Endoscopic Oncology, Division of Respiratory Medicine, Department of Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada. Reprint requests: Norman E. Marcon, MD, Center for Therapeutic Endoscopy and Endoscopic Oncology, Victoria Wing 16-062, St. Michael’s Hospital, Toronto, Ontario, Canada M5B 1W8. Copyright Ó 2004 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(04)01734-1 468
GASTROINTESTINAL ENDOSCOPY
Figure 1. A, ‘‘Spider’’ telangiectasias on neck, upper chest, bilateral shoulders, and upper extremities distributed symmetrically in C3 to T3 dermatomes. B, Close view of vascular lesions, which blanch with pressure. (Fig. 1). These vascular lesions blanched with pressure. There were a few small telangiectasias on the lower lip and gum, but no telangiectasia was found on the buccal mucosa. Except for the telangiectasias, there were no stigmata of chronic liver disease. Chest and precordial examinations were normal. Abdominal and obstetric examinations were appropriate for gestational age. Laboratory test results included normal leukocyte and platelet counts. Tests of liver, renal, and thyroid function were within normal ranges. There was no evidence of intra- or extravascular hemolysis: the peripheral blood smear, serum haptoglobin level, and direct and indirect Coombs’ tests were normal. The serum ferritin level was less than 6 lg/L (12-192 lg/L); iron saturation was 4% (0.20-0.50%). Serologic tests for hepatitis B and C, HIV antibody, and antinuclear antibody were negative. The serum compliment levels and coagulation profile also were within normal limits. At EGD, the entire stomach was studded with non-bleeding telangiectasias. A lung ventilation/perfusion scan and duplex US study of the lower extremities were negative for thromboembolic disease. With a tentative diagnosis of HHT, the patient then was transferred to our institution for further management. EGD was repeated and again revealed studding of the entire gastric and duodenal mucosa with angioectasias, many of which were oozing blood (Fig. 2). The surrounding mucosa appeared normal and was not friable. There were no esophageal varices or evidence of portal hypertensive gastropathy (PHG). Push enteroscopy and colonoscopy were not performed because of the late stage pregnancy and VOLUME 60, NO. 3, 2004
Bilateral nevoid telangiectasia syndrome
the diagnostic findings on EGD. Endoscopic therapy was not attempted because of the diffuse nature of the angioectasias, presumed involvement of the more distal small bowel, and the probable etiologic relationship between the findings and the elevated estrogen state during pregnancy. Treatment was supportive with reference to the GI bleeding. The plasma estradiol level was greater than 1835 pmol/L (basal level in women, 70-220 pmol/L), and progesterone level 1240 nmol/L (normal value during luteal phase, 6-64 nmol/L; during follicular phase, <6 nmol/L). The hospital course was later complicated by high output cardiac failure. The patient complained of significant dyspnea (blood oxygen saturation 90%). As part of the evaluation for HHT, cardiac US with bubble contrast study suggested mild intrapulmonary shunting; valvular regurgitation and vegetation were not noted. Pulmonary angiography failed to demonstrate any pulmonary arteriovenous malformation. Mesenteric Doppler US disclosed no evidence of intrahepatic shunting. The dyspnea was attributed to congestive heart failure caused by fluid overload, a high cardiac output state related pregnancy, GI bleeding, and blood transfusion. Subacute infectious endocarditis with leukocytosis and abnormal tests of liver function developed 3 weeks after admission. Laboratory data were the following: leukocyte count, 10.73 3 109/L (3.0-10.0 3 109/L); platelet count, 236 3 103/cm (140-440 3 103/cm); total bilirubin, 0.2 mg/dL (0.3-1.2 mg/dL); alkaline phosphatase, 89 U/L (35110 U/L); alanine aminotransferase, 60 U/L (5-40 U/L); aspartate aminotransferase, 70 U/L (5-40 U/L); serum albumin, 2.3 g/dL (3.7-4.8 g/dL); and international normalized ratio, 1.0. Blood cultures grew Streptococcus milleri that was sensitive to penicillin. The first EGD had been performed without prophylactic administration of antibiotics. Echocardiography demonstrated severe aortic regurgitation with possible valvular vegetations. Urgent cesarean section was carried out (30 weeks’ gestation). The aortic valve was successfully replaced 1 month after delivery. Histopathologic examination of the resection specimen revealed a congenital bicuspid aortic valve. The eruptive cutaneous telangiectasias resolved completely within 3 weeks after delivery. At EGD 10 weeks after delivery, all previously noted duodenal lesions had completely disappeared and only residual spots of brownish pigmentation were present in the stomach (Fig. 3). The plasma estradiol and progesterone levels had returned within normal limits. EGD at 10 months after delivery revealed fewer and fainter residual pigmentation spots in the stomach. Targeted biopsy specimens of these spots demonstrated only normal gastric mucosa without evidence of angioectasia; Helicobacter pylori were not seen. The final diagnosis was BNTS associated with pregnancy. Mother and baby are doing well.
DISCUSSION 1
Selmanowitz first suggested the term UNTS in 1970.6 To date, less than 70 cases of UNTS have been VOLUME 60, NO. 3, 2004
S-j Tang, M Faughnan, N Marcon
Figure 2. A, Endoscopic view showing numerous ‘‘spider’’ angioectasias, many oozing blood, in fundus of stomach. B, Endoscopic view of ‘‘spider’’ angioectasias in antrum.
reported in dermatologic publications. Only a few congenital cases have been published, and UNTS is not considered a familial disease.6 In general, cutaneous telangiectasias develop unilaterally in the C3 to T3 dermatomal distributions. There are cases of UNTS in which the lower thoracic dermatomes were involved. A review of 44 cases found right and left side involvement in 26 and 18 cases, respectively.6 It has been suggested that the unilateral dermatomal distribution of the telangiectasias relates to a congenitally fixed distribution of target end organs or tissues because of cutaneous morphogenesis patterns sensitive to estrogen.6,7 In some reported cases, skin biopsy specimens of the affected and of unaffected areas were obtained for estrogen and progesterone receptor assay.7,9,11 However, it is difficult to interpret the results, because of the sensitivity of the assays and the low level of estrogen receptor expression in normal skin.8 The telangiectasia in UNTS can be spider, linear, and wiry in GASTROINTESTINAL ENDOSCOPY
469
S-j Tang, M Faughnan, N Marcon
Figure 3. A, Endoscopic view at 10 weeks after delivery, showing numerous residual pigmented spots in gastric antrum. B, Close view of residual pigmented spots.
shape. On microscopic examination, dilated vessels are located in the middle to upper dermis without apparent endothelial proliferation.2,4,5 Patients with nevoid telangiectasia syndrome generally are asymptomatic or only have symptoms associated with a disease or physiologic state, such as hepatic cirrhosis and pregnancy. In addition, laboratory tests are within the normal limits in nevoid telangiectasia syndrome. As in the present case, the most common condition associated with UNTS is pregnancy.6 During normal pregnancy, maternal plasma levels of estrogen rise until term, reaching a mean level of 58,736 pmol/L (normal basal level in women: 20-60 pmol/L). In patients with UNTS, the telangiectasias usually resolve within 4 to 8 weeks after delivery. If it develops during pregnancy, UNTS is reversible but can recur in the same dermatomal distribution with subsequent pregnancies.6 Our patient apparently developed similar lesions during her first pregnancy. 470
GASTROINTESTINAL ENDOSCOPY
Bilateral nevoid telangiectasia syndrome
The greater severity and the widened distribution of the cutaneous lesions during the second pregnancy suggest increased target tissue sensitivity to estrogen after the first pregnancy. Wilkin et al.6 described several patients with UNTS who developed cutaneous telangiectasias with consecutive pregnancies, with resolution between pregnancies. Pregnancy also is associated with occasional sporadic cutaneous telangiectasias in a non-dermatomal distribution. This condition is common and has no clinical significance. Several aspects of the present case are similar to UNTS: the typical dermatomal distribution of the telangiectasias, the temporal and the probable etiologic relationship with elevated estrogen state, normal laboratory tests, and recurrence of skin lesions during the second pregnancy. However, it also differs from UNTS in two ways: the bilateral distribution and the GI-tract involvement. To our knowledge, this is the first case of BNTS in which GI involvement was documented. However, it is not known whether the GI involvement is unique to BNTS or if occult GI involvement occurs in UNTS. The differential diagnosis of nevoid telangiectasia syndrome includes HHT and generalized essential telangiectasia (GET). HHT is an inherited (autosomal dominant) disorder characterized by mucocutaneous telangiectasia and visceral involvement.12–14 Two distinct genes have been found to be the cause of HHT: endoglin mutated in HHT1 and activin receptor-like kinase 1 (ALK-1) mutated in HHT2.12 Of patients with HHT, 80% to 90% have a family history of the disorder.13 The vast majority of adult patients have recurrent spontaneous epistaxis.13 Currently, the diagnosis of HHT requires that 3 of 4 criteria be met: epistaxis, mucocutaneous telangiectasia, family history, and well-documented visceral involvement.14 The typical telangiectasias in HHT are punctiform and are most commonly found on the face, the mouth, and the hands.13 In our experience, ‘‘spider’’ telangiectasias are not commonly found in patients with HHT. In HHT, GI bleeding generally occurs until the 5th or 6th decade.12 Although the telangiectasias of HHT often become more prominent during pregnancy, they do not have a dermatomal distribution and do not resolve after delivery. In our patient, the negative family history of HHT, the absence of recurrent epistaxis, the dermatomal distribution of telangiectasias, and the resolution after delivery make HHT unlikely. In GET, the cutaneous telangiectasias are characteristically linear, mottled, or net-like. These vascular lesions appear most commonly on the lower extremities and buttocks; there is no spontaneous bleeding or visceral involvement. One reported patient with GET had GI VOLUME 60, NO. 3, 2004
Bilateral nevoid telangiectasia syndrome
bleeding caused by gastric antral vascular ectasia (GAVE).15 GET occurs most commonly in women and is likely not related to UNTS, although there is some speculation that GET may represent a generalized form of the same pathologic process as UNTS.6 Our patient had numerous GI angioectasias that regressed completely after delivery. GI involvement has not been reported in patients with UNTS without hepatic cirrhosis.6 A single case of gastric angioectasias in a patient with UNTS and hepatic cirrhosis has been reported.4 Non-bleeding angioectasias were noted in the stomach in the patient with alcoholic cirrhosis. However, portal hypertension can cause gastric varices and PHG.16,17 GAVE and gastric angioectasias can be observed in patients with cirrhosis without UNTS.18 Furthermore, in severe PHG, cherry-red spots or patches are frequently present, which mimic angioectasias. The vascular ectasia in PHG is believed to arise from the dilated mucosal and submucosal capillaries and veins.19,20 In our patient, there was no evidence of underlying liver disease or hepatic cirrhosis. Complete resolution of these lesions, as documented endoscopically, is strong evidence that these lesions were related to the elevated estrogen level during pregnancy. To our knowledge, this is the first case reported of the BNTS with GI involvement and of a nevoid telangiectasia syndrome in the absence of cirrhosis. The mucocutaneous telangiectatic lesions regressed after delivery. An elevated estrogen level can be associated with reversible angioectasia in the GI tract. Expectant supportive management until delivery is feasible and should be recommended. Antibiotics should be administered prophylactically before endoscopy if this syndrome is suspected, as well as in patients with HHT. Although endoscopic intervention is not feasible if the lesions are diffuse, endoscopy should be performed to rule out other causes of GI bleeding and to evaluate the extent of the GI angioectasias if present. Reversal of elevated estrogen status occasionally is required. REFERENCES 1. Selmanowitz VJ. Unilateral nevoid telangiectasia. Ann Intern Med 1970;73:87-90. 2. Mirrer E, Cipriano A, McGuire J. Unilateral nevoid telangiectasia. Arch Dermatol 1971;103:320-3. 3. Selmanowitz VJ. Unilateral nevoid telangiectasia. Arch Dermatol 1972;105:131.
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S-j Tang, M Faughnan, N Marcon
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