Gut, 1988, 29, 1408-1412

Case report

Blue rubber bleb naevus disease: an uncommon causeof gastrointestinal tract bleedingM JENNINGS, P WARD, AND J L MADDOCKS

From the University Department ofPharmacology and Therapeutics, and Department ofRadiology, RoyalHallamshire Hospital, Sheffield

SUMMARY A 23 year old woman presented with facial pain, a right parotid tumour and irondeficiency anaemia. She had several cutaneous venous swellings and tumours with a similarappearance were found in the large bowel. Histological examination of the parotid tumour andangiography of the skin and gut lesions confirmed that they were venous in origin. The aetiology,classification, and complications of disorders of the venous system and the importance of using atourniquet to examine the peripheral veins is discussed.

There is an ill defined group of conditions character-ised by the coexistence of lesions in both the skin andthe internal organs. For example, in blue rubber blebnaevus disease haemangiomas in the skin are associ-ated with vascular polyps in the bowel. The lattermay give rise to occult or frank gastrointestinal tractbleeding resulting in anaemia.We have recently investigated a woman who

presented with anaemia and a unilateral parotidswelling. She also had unusual skin lesions whichseemed to arise from veins, and we found vasculartumours with similar appearances in the large bowel.This combination of abnormalities led to the diagno-sis of blue rubber bleb naevus disease. Angiographyconfirmed that the skin and the bowel lesions werepart of the venous system. This case illustrates firstlythat careful examination of the skin of patients withanaemia may reveal the cause, and secondly howdetailed investigation of vascular lesions helps inclassification.

Case history

A 23 year old shop assistant initially visited hergeneral practitioner because of heavy menstrualbleeding. He thought she was anaemic and pre-scribed oral iron supplements. Three years later, inAddress for correspondence: Dr M Jennings, University Department ofTherapeutics, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF.Received for publication 14 April 1988.

1981, she went to see her dentist because of a painfullump on the right side of her face. The right parotidgland was intermittently swollen and tender, and apresumptive diagnosis was made of parotid ductobstruction caused by calculus. Sialography con-firmed the presence of a stone but surprisingly it layoutside the duct. Subsequent surgical exploration ofthe gland revealed a plexus of veins containing threestones. This region was excised, and histologicalexamination showed a vascular anomaly of angio-matous type in which thrombus had becomeorganised into phleboliths (Fig. 1).She was referred for a medical opinion and was

found to be anaemic (Hb 8.7 g/dl). She denied any

Fig. 1 Section ofparotid gland showing angioma.1408

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Blue rubber bleb naevus disease: an uncommon cause ofgastrointestinal tract bleeding

Fig. 2 Venous varicosity on the dorsum ofthe left hand,with smaller lesions on the ulnar aspect.

blood in her stools, haematemesis, or melaena. Herperiods were regular but heavy. There was no historyof excessive bleeding or bruising. She had stoppedtaking the iron tablets prescribed by her doctor afteronly a few months. Her father had died aged 53 yearsfrom a brain haemorrhage, and she has a sister withepilepsy. Careful examination of her skin revealed anirregular venous varicosity, 1-5 cm in diameter, onthe dorsum of the left hand (Fig. 2). Smaller similarlesions were found on the tongue (Fig. 3), soft palate(Fig. 4), and labia. When a tourniquet was applied toeach forearm, multiple globular venous swellingsbecame visible on the skin surface and the varicosityon her hand became much more prominent. A portwine stain was found on the nape of her neck (Fig. 5).The blood film showed a microcytic hypochromic

picture, and three specimens of faeces were positivefor occult blood. A barium enema showed two smallpolyps, one at the splenic flexure (Fig. 6), and theother just proximal to the hepatic flexure. At colono-scopy two vascular polyps were seen, each 1 cm indiameter, the first in the rectum, and the second atthe splenic flexure. There were three other tiny

_Li.-

Fig. 3 The undersurface ofthe tongue.

similar lesions in the descending colon. Initially theproximal half of the transverse colon and the ascend-ing colon were not visualised because the patientcomplained of pain. At a subsequent examination,however, the tumour at the hepatic flexure was seen.The lesions were not biopsied because of their veryvascular appearance and thus the fear of serioushaemorrhage. At gastroscopy, the stomach andduodenum were normal. Plain radiographs revealedphleboliths on both sides of the face, in the neck, andthe lung apices (Fig. 7). Arteriography with selectiveinjection of the mesenteric vessels showed a collec-tion of venous spaces in the region of the hepaticflexure (Fig. 8). In view of the family history of brainhaemorrhage, cerebral arteriography was under-taken to exclude an intracranial vascular anomaly,but none was seen. Venography of the forearmvessels showed widespread tiny venous aneurysms,and a larger plexiform lesion (Fig. 9) which corres-ponded to the venous swelling seen on the skin.She was transfused with blood but she also

required oral iron supplements because of continuedoccult bleeding from the bowel. Apart from occa-sional pain and swelling over the right cheek she

Fi. 4Fig. 4 Lesions on the softpalate.

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Fig. 5 Port wine stain on the neck.

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Jennings, Ward, and Maddocks

_S ~~~~~~~~~~~~~~......

Fig. 6 Double contrast barium enema showing a smallpolyp at the splenicflexure.

remained well for almost three years. She thenpassed three melaena stools and the haemoglobin fellto 6-1 g/dl. We referred her to Dr N Krasner, WaltonHospital, Liverpool, for laser treatment of thecolonic tumours. This was started in July 1987 afterblood transfusion and her haemoglobin is now stable.

Discussion

Blue rubber bleb naevus disease is an uncommoncondition in which haemangiomas in the skin areassociated with intestinal haemorrhage from similarlesions in the gut.' It was probably first reported byGascoyen2 in 1860. He described a man who pre-

Fig. 7 Chest radiograph. Small calcified opacities at theapices.

Fig. 8 Subtraction film ofsuperior mesenteric arteryangiogram showing a collection of venous spaces in the wallof the colon (->).

sented with a congenital tumour of the parotid, andwho died from suffocation after gross enlargement ofthe tumour. At necropsy there were cutaneous naevidistributed widely over the skin surface, with similar

Fig. 9 Forearm venography shows widespread varicosities,the largest (->) corresponding to the skin lesion shown inFig. 2.

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Blue rubber bleb naevus disease: an uncommon cause ofgastrointestinal tract bleeding

lesions 'studding the surface of the intestines'. Theparotid tumour was composed of tortuous anddilated blood vessels many of which containedphleboliths. There have been about 20 furtherreports of the syndrome. The term 'blue rubber blebnaevus' was introduced by Bean' in 1958 because thecutaneous lesions 'have the look and feel of rubbernipples, are compressible and refill fairly promptlyfrom their rumpled and compressed state'.The principal sites of involvement are the skin, and

the gut' including the oral mucous membrane,7although lesions in the liver, lung, and skeletalmuscle have been found at necropsy.8 Apart fromGascoyen's original description there have been noother reports of salivary gland involvement. Walsheet al' ascribed the occurrence of haematuria andepistaxis in their patient to bladder and upperrespiratory tract involvement respectively, but theirinvestigations failed to show the presumptivevascular tumours. Our patient was found to havelesions in the skin, large bowel, and parotid gland.We presume that the phleboliths seen on the chestradiographs indicate involvement of the lungs also.The appearances of cutaneous naevi in this conditionmay not be uniform. Bean' described three morpho-logical types of lesion: large cavernous angiomas,blue rubber blebs, and an irregular blue mark of theskin. The number and distribution of lesions on thebody surface is also variable.

Naevi tend to appear during the first few years oflife, and may subsequently enlarge and give rise tovarious complications. Some patients have com-plained of painful lesions.7'81 This may be because ofthe contraction of smooth muscle fibres surroundingthe vascular tumours." Excessive sweating fromoverlying skin has been accounted for by the closeanatomical association between naevi and sweatglands.` Our patient has not noticed local sweating,but did experience pain over the facial swelling. Thismay have been because of stretching of the capsule ofthe parotid gland rather than having arisen directlyfrom the angioma.Thrombosis and secondary calcification may occur

within the naevi. In our patient we found thrombosisand phlebolith formation in the parotid tumour andcalcification on the chest film. Because the vascularpolyps seen through the colonoscope did not fill withcontrast during angiography we think that they alsomay have thrombosed. An association with pul-monary hypertension has been suggested,'` possiblyarising through in situ thrombosis and obliteration ofthe pulmonary vascular bed. A further potentialproblem is platelet consumption which has beendescribed in association with single large cavernoushaemangiomas. 14

Blue rubber bleb naevus disease has been seen in

successive generations,'` and an autosomal dominantmode of inheritance postulated. '̀1" We can find noevidence of the condition in the first degree relativesof our patient. Her father died of a brain haemorr-hage but he did not have skin lesions, and we think itunlikely that he had blue rubber bleb naevus disease.The commonest mode of presentation is with gastro-intestinal tract bleeding from vascular tumours in thelarge4' and small bowel.'6 6 ` The skin lesions areusually obvious, although in our patient the smallerones were visible only after the application of atourniquet.

In view of the appearance of the cutaneous lesionsand the pattern of organ involvement we think thatour patient has blue rubber bleb naevus disease. Shedoes not have the telangiectasia on the face, lips, andnails characteristic of hereditary haemorrhagictelangiectasia. Although she has a port wine stain onher neck, there is no underlying intracranialhaemangioma such as one might expect if she hadeither Sturge-Weber'8 or Von-Hippel Lindaudisease.'9 We felt that as we had the histology of theparotid gland, further biopsies of either the skin orthe bowel lesions were unnecessary and possiblyhazardous. We considered detailed radiologicalinvestigation to be essential, however, to determinethe morphological site and anatomical distribution ofthe abnormalities. We were particularly concernedabout the possibility of an intracranial lesion. Thismay have required treatment, and would haveprompted counselling with regard to the risk ofbleeding in future pregnancy.

Selective mesenteric angiography revealed acollection of venous spaces at the hepatic flexure.The other polyps in the colon were not seen possiblybecause of in situ thrombosis. The angiographicappearance of the cutaneous lesions in blue rubberbleb naevus disease has not, so far as we are aware,been previously documented. We have demon-strated venous varicosities in the forearms whichcorresponded to the observed skin lesions, and wetherefore think that blue rubber bleb naevus diseaseshould be regarded as a disorder of the venoussystem.The problem of classifying venous disorders has

been approached in different ways. Lea Thomas andAndress`' divided venous dysplasias of the limbs intotwo groups on the basis of their angiographicappearances: phlebectasia, in which the principalabnormality is dilated venous trunks, and venousangiomas, which consist largely of cavernous spaces.Malan and PuglionisiP' adopted an embryologicalapproach and defined four categories; phlebectasia,phlebangioma, phlebangiomatosis, and combina-tions of the three further divided for site and extent.The lesions of blue rubber bleb naevus disease

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1412 Jennings, Ward, and Maddocks

Table Distribution of lesions

Type ofLesion Cutaneous Visceral

Capillary Capillary angioma('strawberry naevus')

Naevus flammeus Osler-Weber-Rendu('port-wine stain') (GI tract and lung)

Sturge-Weber (Meninges)Cobb (Spinal cord)

Venous Cavernous angioma Von Hippel-Lindau(Central nervous system)

GorhamMaffuciBlue rubber bleb naevus(GT tract and lung)

probably correspond to the venous angiomas orphlebangiomatosis described by these authors.There are clinical syndromes in which dilatation of

major veins is the principal abnormality. TheKlippel-Trenauney syndrome22 for example, is thetriad of varicose veins, limb hypertrophy, andcutaneous haemangioma confined to one extremity.Parkes-Weber"3 described a similar condition com-plicated by an A-V fistula. Involvement of the viscerais not found in these conditions.From the clinical standpoint the classification of

such syndromes is ill defined. There are severalconditions in which vascular lesions in the skin areassociated with similar lesions in other organs. Thelatter may be: the meninges, in Sturge-Weber; thebrain and retina in von-Hippel Lindau; the spinalcord as described by Cobb24; and the skeleton byGorham25 and Maffucci26; or the gut and lung inOsler-Weber-Rendu disease. Blue rubber blebnaevus disease is clearly a disorder which shares thispattern of cutaneous and visceral involvement. Inthis respect it most closely resembles Osler-Weber-Rendu disease, but the two may be distinguished bythe very different appearance of the skin lesions. It isof interest that in both conditions abnormalities mayalso be found in the lungs, which of course share theirembryological origins with the foregut. We haveattempted a simple classification of these disorders(Table).

References

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2 Gascoyen GG. Case of naevus involving the parotidgland and causing death from suffocation: naevi of theviscera. Trans Pathol Soc London 1860; 11: 267.

3 Bean WB. Vascular spiders and related lesions of theskin. Springfield, Ill: Charles C Thomas, 1958.

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18 Sturge WA. A case of partial epilepsy apparently due toa lesion of one of the motor centers of the brain. TransClin Soc London 1879; 12: 112.

19 Lindau A. Studien uber kleinhirncysten Bau, Patho-genese und Beziehungen zur Angiomatosis Retinae.Acta Pathlol Microbiol Scand 1926; suppl: 1-128.

20 Lea Thomas ML, Andress MR. Angiography in venousdysplasias of the limbs. Am JRoentgenol 1971; 113: 722-73.

21 Malan E, Puglionisi A. Congenital angiodysplasias ofthe extremities I. Generalities and classification; venousdysplasias. J Cardiovasc Surg 1964; 5: 87-130.

22 Klippel M, Trenauney P. Nevus variqueux osteo-hypertrophique. Arch Gen Med 1900; 3: 641-72.

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24 Cobb S. Haemangioma of the spinal cord associatedwith skin naevi of the same metamere. Ann Surg 1915;62: 641-9.

25 Gorham LW, Wright AW, Schultz HH, Maxon FC.Disappearing bones; a rare form of massive osteolysis.Am J Med 1954; 17: 674.

26 Carlton A, Elkington JStC, Greenfield JG, Robb-SmithAHT. Maffucci's syndrome. Q J Med 1942; 11: 203-28.

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