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694 Gut, 1991, 32, 694-697

PROGRESS REPORTS Gut: first published as 10.1136/gut.32.6.694 on 1 June 1991. Downloaded from

Skin and gullet

S Walton, J R Bennett

Diseases ofthe skin and gullet coexist more often aetiological agent should be identified and dealt than would be expected by chance, though with appropriately. perhaps no more than one might expect consider- ing the ectodermal origin of the oesophageal mucosa. Several types of interaction betwen the (3) ACQUIRED IMMUNODEFICIENCY SYNDROME skin and the oesophagus are possible: (AIDS) (1) The skin disease is the cause ofoesophageal This syndrome was first reported in male homo- disease; sexuals in the United States in 1981. Severe (2) The skin and oesophageal disease have a opportunistic infections and uncommon malig- common pathology; nancies occur against a background of profound (3) The two are indirectly related as in the T cell immunosuppression in a previously genetic orocutaneous syndromes. healthy adult. Identification ofthe relation is important, both Oesophageal and dermatologic manifestations for understanding and clinical management, of AIDS are secondary to the severe T cell although some cutaneo-oesophageal relations immunodeficiency and, in most instances, can be cannot, at present, be categorised into these related to the presence ofopportunistic infection. groups as our knowledge is insufficient. Chronic candidal infection of the mucous mem- This review will deal with changes in the skin branes may result in erosive oesophagitis.' that are associated with disease in the oeso- and cytomegaloviruses have pro- phagus, contributing to the common symptom duced oesophageal ulcers`' and oesophagitis,` http://gut.bmj.com/ triad ofdysphagia/heartburn/acid regurgitation. both in immunocompetent homosexual men and patients infected with the human immuno- deficiency virus, HIV. Kaposi's sarcoma can Oro-oculo-genito-cutaneous syndromes occur on the skin or mucous membranes. Topical treatment is ineffective for (1) BEHCET'S DISEASE oesophageal candida, and systemic antifungal The diagnosis of this heterogeneous disease agents are usually required. There is little to on September 24, 2021 by guest. Protected copyright. depends on the identification of its more typical choose between the new expensive triazole, clinical features. The recently revised diagnostic fluconazole, and the imidazole, ketoconazole. criteria' include recurrent oral ulceration and two Intravenous foscarnet heals cytomegalovirus of the following: recurrent genital ulcers, eye ulceration of the oesophagus with long term involvement (uveitis or ), skin mani- remission of symptoms for up to six months. festations (erythema nodosusm or papulo- Ganciclovir is also effective but may produce pustular/acneiform lesions), and a positive granulocytopaenia. Acyclovir is used for the pathergy test. treatment of herpetic oesophagitis and the Oesophageal involvement is rare. Erosions, ulceration/leucoplakia caused by infection with perforated ulcers, widely spreading oesophagitis, Epstein-Barr virus or papilloma virus.0 and severe stenosis have been described.2 There is no specific treatment and steroids are oflimited value. Our own experience suggests that colchi- Bullous disorders cine is useful in patients with oral, genital, and ocular disease.3 Treatment has to be individually (1) VULGARIS tailored to the patient rather than standardised This is the most serious of the bullous diseases for all patients. and was often fatal before systemic corticosteroid treatments were available. Blisters are wide- spread and occur within the epidermis. Mucosae (2) STEVENS-JOHNSON SYNDROME are often affected, although blisters break easily Departments of and erosions are the main in the Dermatology and In Stevens-Johnson syndrome (the bullous- physical sign Gastroenterology, Hull erosive variant of ) dys- mouth. Extensive use of endoscopic fibreoptic Royal Infirmary, Hull phagia may result from ulceration of buccal, techniques has shown that oesophageal involve- S Walton pharyngeal, and oesophageal mucosae. Very ment of pemphigus vulgaris is not as rare as J R Bennett rarely, bullae and eosinophilic necrosis of the previously thought. The various oesophageal Correspondence to: Dr J R Bennett, Hull Royal oesophagus have been described.4 Treatment is changes described include the presence of Infirmary, Anlaby Road, Hull usually symptomatic, although severe cases may erosions, bullae," and a condition called HU3 2JZ. need for steroid treatment 'oesophagitis dissecans superficialis' in which the Accepted for publication hospital admission 17 August 1990 and maintenance of fluid intake. If possible, the patient vomits a cast ofthe oesophageal mucosa. 2 Skin andgullet 695

A histological and immunofluorescent diagnosis oesophageal reflux and hiatus hernia have been is mandatory as oesophageal involvement may observed in the recessive dystrophic variant of necessitate a higher dose of steroids." Candida, EB, contributing to lower oesophageal ulceration herpetic oesophagitis, and peptic disease, which and stricture formation. Disordered or poor Gut: first published as 10.1136/gut.32.6.694 on 1 June 1991. Downloaded from are frequent in steroid treated patients, should be oesophageal peristalsis has also been observed excluded and appropriately treated. As in the during radiological examination. skin, the histological findings of Autosomal recessive dystrophic EB is most (separation of epidermal cells) is associated with frequently associated with extensive lesions of the deposition of immunoglobulin, IgG, anti- the oesophagus and other mucous membranes. bodies and occasionally complement, C3 between The autosomal dominant form of the disease epidermal cells. occasionally results in moderately severe bullous The mainstay of treatment'3 is systemic corti- skin lesions and can be associated with oral, costeroids and immunosuppressive drugs. oesophageal, and anal blistering, although severe Rarely, plasma exchange,'4 chrysotherapy,'5 and erosions and strictures are not a feature. Junc- possibly inorganic arsenic also have a place. Gold tional EB, an autosomal recessive disorder with should be reserved for those patients who either extensive skin blistering and considerable neo- fail to respond to steroids and immunosuppres- natal mortality, can be associated with oral, sion or who cannot tolerate these drugs. 6 oesophageal, and anal blisters. The oesophagus is not usually affected in acquired EB (EB acquisita). (2) PEMPHIGOID There is no definite treatment for the oeso- Blisters, usually widespread, occur at subepider- phageal lesions of EB, Treatment in the acute mal level in - a blistering stage is, therefore, symptomatic and aimed at skin disease of the elderly. Although it may last decreasing bullae formation, preventing aspira- for life, it is more likely to go into spontaneous tion of food and secretions, and maintaining remission than pemphigus. Mouth and other nutrition with hyperalimentation. High dose mucosal lesions occur in bullous pemphigoid but steroids for short periods are sometimes effective are less common than in pemphigus and mucous in relieving dysphagia. Phenytoin is mostly effec- membrane pemphigoid, a distinct variant of tive in the treatment of skin lesions but has pemphigoid, in which mucous membrane lesions benefited some patients with oesophageal in- may be the presenting feature and may occur volvement. The cervical strictures are easily without skin blisters. Confirmation of the dilated but diffuse oesophageal involvement is diagnosis can be obtained by the finding of a more difficult to manage with a considerable risk continuous band of immunoglobulin (IgG) and of perforation from the procedure. Surgical http://gut.bmj.com/ complement (C4) at the dermoepidermal junc- treatment for oesophageal stricture is indicated tion. Oesophageal involvement is rare and has when the lesion is no longer responsive to been reported to include bullae, diffuse oeso- dilatation or if perforation or further strictures phagitis, adhesions, webs, and strictures. 7 Com- occur because of dilatation. Provided adequate plications have included gastrointestinal perioperative attention is given to the patients' haemorrhage'8 and sloughing off of the entire nutrition, skin bullae, and ulceration, colonic oesophageal mucosa as a hollow membraneous interposition either to bypass or replace the on September 24, 2021 by guest. Protected copyright. cast. '9 Although pemphigoid is now not thought strictured oesophageal segment, has been to be statistically associated with malignancy,20 reported with success.24 there is one report of its occurring concurrently with oesophageal carcinoma.2' The treatment of bullous pemphigoid is similar to that of Hyperkeratotic disorders pemphigus vulgaris, with corticosteroid and immunosuppressive drugs, especially azathio- (1) DIFFUSE prine. (TYLOSIS) Howel-Evans et aF5 first reported the association of dominantly inherited tylosis, with carcinoma (3) EPIDERMOLYSIS BULLOSA (EB) of the oesophagus in 48 members of two families Oesophageal disease becomes symptomatic at in Liverpool, who developed tylosis of the late any age and most reported series include patients onset type, 17 of whom developed squamous between infancy and the third decade.22 The oesophageal carcinoma. Since then, various cases types ofoesophageal involvement vary - mucosal of a similar association have been reported. One bullae can be precipitated by the ingestion of study describing 22 members of a south Indian coarse food, causing dysphagia and sometimes farmily, spanning five generations, makes the obstruction ofthe oesophagus leading to regurgi- point that squamous cell carcinoma may also tation of food and bloodstained secretions; oeso- develop in the tylotic skin.26 phageal web formation is a recognised complication of dystrophic EB, due to localised mucosal damage by blistering but it may also be (2) ACANTHOSIS NIGRICANS related to the chronic iron deficiency in EB The skin in this condition is described as warty, caused by blood loss from the skin and gut thickened, and pigmented - changes are most coupled with inadequate dietary intake;23 noticeable in the flexures but can affect any area oesophageal strictures pose a major problem with of the body including mucous membranes. about halfoccurring in the proximal oesophagus, Endoscopy on one occasion showed a warty a quarter in the lower oesophagus, and the oesophageal surface caused by mucosal thicken- remainder occurring at multiple sites; gastro- ing.27 696 Walton, Bennett

There is suggestion of a circulating epidermo- reported. When severe oesophageal disease is trophic growth factor in acanthosis nigricans that found, steroid treatment should be started to is similar in structure to urogastrone, and this is reduce the symptoms and any strictures and particularly interesting in view of the predomi- possibly to decrease any risk of malignant trans- Gut: first published as 10.1136/gut.32.6.694 on 1 June 1991. Downloaded from nance ofgastric cancers in this condition. formation.303'

(3) DARIER'S DISEASE (KERATOSIS FOLLICULARIS)28 Collagen vascular diseases This condition is determined by an autosomal dominant gene with variable penetrance. The (1) SYSTEMIC SCLEROSIS distinctive skin lesion is a firm, greasy, crusted The cutaneous changes32 affect the face and papule, the colour varying from skin coloured to hands most frequently, though the changes may yellowish brown. Coalescence of these papules extend to affect the skin generally. The facial produces irregular warty plaques or appearance is characteristic. Small mat like papillomatous masses affecting the seborrhoeic are frequently found on the face areas of the face and trunk. On the palms and and hands - the hands and fingers being swollen soles there may be punctate keratoses or minute and tumid in early disease, evolving into atrophic pits which are pathognomonic. The nails show changes as the disease progresses. Small painful longitudinal ridging with a V shaped nick at the ulcers on the fingers heal leaving depressed scars free margin. and are sometimes associated with gangrenous Lesions ofthe mucous membranes are uncom- changes and discharge of calcium deposits from mon and white umbilicate or 'cobblestone' time to time. Other skin changes include gener- papules on the tongue, oropharynx, oesophagus, alised pigmentation resmbling Addison's rectum, and vulva may be associated with gin- disease, slow healing leg ulcers, livedo reti- gival hypertrophy. Confluence of the papules cularis, and small white areas of atrophie may simulate . blanche. Most patients with Darier's disease become Oesophageal motility is shown to be abnormal symptomatic by the third decade, though the by radiology in about 66% but manometric disease can start at the age of 10 years. The changes are found in up to 85% of patients. diagnosis is essentially clinical, though distinc- Manometric abnormalities include absent peri- tive histological changes in the skin include stalsis of the smooth muscle oesophagus and a suprabasal lacunae, epidermal with reduced lower oesophageal sphincter pressure.

the formation of'corps ronds' and 'grains', and a The upper oesophageal sphincter pressure is http://gut.bmj.com/ variable degree of , normal and peristalsis may be preserved in the and acanthosis. upper 4 to 5 cm.33 The main oesophageal symp- Treatment of the skin is largely symptomatic toms are of gastro-oesophageal reflux and dys- with the use of simple emollients or aromatic phagia, suggesting the development of a retinoids for severe disease. No specific therapy stricture. However, a third of affected patients is known to help mucosal lesions. have no oesophageal symptoms. Strictures occur

in approximately 10% of patients and carcinoma on September 24, 2021 by guest. Protected copyright. of the oesophagus has been reported.32 (4) The cause of lichen planus remains unknown. The characteristic skin lesion is a tiny, flat (2) DERMATOMYOSITIS topped, shiny, violaceous papule, often seen with The rash in well developed cases is diagnostic. a network of delicate white lines on its surface Purplish red heliotrope oedema affects the upper known as Wickham's striae. Lesions are usually half of the face, mainly the eyelids, but may also distributed symmetrically and bilaterally over be found on the hands and other areas of the flexor surfaces of the forearms and wrists, neck, body. Scaly, bluish red plaques on the back ofthe legs, and lower back. Oral mucous membranes fingers, especially over the knuckles, are some- and genitalia are also affected. Healing sites may times seen as dilated and tortuous nail fold show striking hyperpigmentation. Histologi- capillary loops. Ragged cuticles, as in other cally, the papule oflichen planus shows thicken- collagen vascular diseases, are sometimes a fea- ing of granular layer, liquefaction degeneration ture. of basal layer, and a band like lymphohistiocytic Dysphagia is a prominent symptom attributed infiltrate in the upper dermis. Pigmentary incon- to involvement ofthe muscles ofthe pharynx and tinence and 'Civatte bodies' may be seen in the oesophagus in a fashion similar to involvement of dermis. proximal skeletal muscles. Diverticular out- Oesophageal disease may result in dysphagia pouching of the oesophagus can develop as a and the formation of benign strictures. The result of the muscle weakness.32 Regardless of prevalence of oesophageal disease has been whether there is an underlying neoplasm, a greatly underestimated in the past. In our most myopathy, especially when it involves muscles of recent endoscopic study, we found that a quarter swallowing, is an indication for urgent treatment of patients with lichen planus had oesophageal with adequate doses of systemic corticosteroids involvement in the form of papular lesions, and sometimes azathioprine as well. though severe erosive changes were rare.29 In view of the increased risk of malignant change 1 International Study Group For Behset's Disease. Criteria for with oral lichen planus,3' chronic erosive changes diagnosis of Behset's disease. Lancet 1990; 335: 1078-80. of lichen planus in the oesophagus may also be 2 Moni S, Yoshihira A, Kawamnura H, et al. Esophageal involve- premalignant, although no such cases have been ment in Behset's disease. AmJ Gastroenterol 1983; 78: 548- Skin andgullet 697

3 Muzulu SI, Walton S, Keczkes K. Coichicine therapy in 19 Foroozan P, Enta T, Winship D, et al. Loss and regeneration Behcet's syndrome - a report of 5 cases. Clin Exp Dertnatol of the esophageal mucosa in pemphigoid. Gastroenterology 1989; 14:298-9. 1967; 52: 548-58. 4 Heer M, Altorfer J, Burger H, et al. Bullous esophageal lesions 20 Lindelof B, Islam N, Eklund G, et al. Pemphigoid and cancer.

due to cotrimoxazole: an immune-mediated process? Gastro- Arch Dermatol 1990; 126: 66-8. Gut: first published as 10.1136/gut.32.6.694 on 1 June 1991. Downloaded from enterology 1985; 88: 1954-7. 21 Furukawa F, Ozaki M, Imamura S, et al. Bullous pemphigoid 5 Ammann AJ, Cutaneous manifestations of immunodeficiency associated with radiotherapy for esophageal carcinoma. disorders. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freed- Dermatologica 1981; 162: 451-4. berg IM, Austen KF, eds. Dermatology in general medicine 22 Gryboski JD, Touloukian R, Campanella RA. Gastrointestinal (3rd ed). New York: McGraw-Hill Book Company, 1987: manifestations of epidermolysis bullosa in children. Arch 2517-9. Dermatol 1988; 124: 746-52. 6 St Onge G, Bezahler GH. Giant esophageal associated 23 Tidman MJ, Martin IR, Wells RS, et al. Oesophageal web with cytomegalovirus. Gastroenterology 1982; 83: 127-30. formation in dystrophic epidermolysis bullosa. Clin Exp 7 Rabeneck L, Boyko WJ, McLean DM, et al. Unusual Dermatol 1988; 13: 279-81. esophageal ulcers containing enveloped virus like particles in 24 Touloukian RJ, Schonholz SM, Gryboski JD, et al. Periopera- homosexual men. Gastroenterology 1986; 90: 1882-9. tive considerations in esophageal replacement for epider- 8 Solammadevi SV, Patwardhan R. Herpes esophagitis. Am J molysis bullosa: report oftwo cases successfully treated with Gastroenterol 1982; 77: 48-50. colon interposition. Am J Gastroenterol 1988; 83: 857-61. 9 Villar LA, Massanari RM, Mitros FA. Cytomegalovirus 25 Howel-Evans W, McConnell RB, Clarke CA, et al. Carcinoma infection with acute erosive esophagitis. AmjMed 1984; 76: of the oesophagus with keratosis palmaris et plantaris 924-8. (tylosis). QJMed 1958; 27: 413-29. 10 Gazzard BG. Practical advice for the gastroenterologist dealing 26 Yesudian P, Premalatha S, Thambiah AS. Genetic tylosis with with symptomatic HIV disease. Gut 1990; 31: 733-5. malignancy: a study of a south Indian pedigree. Br J 11 Goldin E, Lijovetzky G. Esophageal involvement by Dermatol 1980; 102: 597-600. pemphigus vulgaris. Am J Gastroenterol 1985; 80: 828-30. 27 Walton S, Krause L, Marks J. A case ofacanthosis nigricans - 12 Kaplan RP, Touloukian J, Ahmed AR, et al. Esophagitis aninvestigativeapproach. ClinExpDermatol 1984;9: 58-63. dissecans superficialis associated with pemphigus vulgaris. 28 Wilkinson JD, Darier's Disease. In: Rook A, Wilkinson DS, J Am Acad Dennatol 1981; 4: 682-7. Ebling FJG, Champion RH, Burton JL, eds. Textbook of 13 Walton S, Marks J. Bullous eruptions: advances in under- dermatology (4th ed). Oxford: Blackwell Scientific Publica- standing and treatment. Update 1985; 30: 1263-7. tions, 1986: 1439-43. 14 Walton S, Keczkes K, Robinson AE. A case of penicillamine- 29 Dickens CM, Heseltine D, Walton S, et al. The oesophagus in induced pemphigus successfully treated by plasma lichen planus: an endoscopic study. BMJ 1990; 300: 84. exchange. Clin Exp Dernnatol 1987; 12: 275-6. 30 Jobard-DrobacheffC, Blae D, Quencez E, et al. Lichen planus 15 Walton S, Keczkes K. Pemphigus foliaceous - successful ofthe oesophagus. Clin Exp Dermatol 1988; 13: 38-41. treatment with adjuvant gold therapy. Clin Exp Dermatol 31 Sheehan-Dare RA, Cotterill JA, Simmons AV. Oesophageal 1987; 12:364-5. lichen planus. Brj Dermatol 1986; 115: 729-30. 16 Pye RJ. Bullous eruptions. In: Rook A, Wilkinson DS, Ebling 32 Rowell NR. erythematosus, and derma- FJG, Champion RH, Burton JL, eds. Textbook ofdermatol- tomyositis: the 'collagen' or 'connective-tissue' diseases. In: ogy (4th ed). Oxford: Blackwell Scientific Publications, Rook A, Wilkinson DS, Ebling FJG, Champion RH, Burton 1986: 1637. JL (eds). Textbook ofdermatology (4th ed). Oxford: Blackwell 17 Agha FP, Raii MR. Esophageal involvement in pemphigoid. Scientific Publications, 1986: 1352-6. GastmintestRadiol 1982; 7:109-12. 33 Weihrauch TR, Korting GW. Manometric assessment of 18 Eng TY, Hogan WJ, Jordan RE. Oesophageal involvement in oesophageal involvement in progressive systemic sclerosis, bullous pemphigoid: a possible cause of gastrointestinal morphoea and Raynaud's disease. BrJ Dermatol 1982; 107: haemorrhage. BrJ Dermatol 1978; 99: 207-10. 325-32. http://gut.bmj.com/ on September 24, 2021 by guest. Protected copyright.