British Journal of Dermatology (1975) 93, 465.
Case Report
Lichen planus and ulcerative colitis EDWARD H.WYATT Department of Dermatology, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ Accepted for publication 24 January 1975
SUMMARY
Three patients with ulcerative colitis and lichen planus are reported and similar cases in the literature discussed. Similarities in the pathology of the two conditions are outlined.
Ulcerative colitis patients have been seen who developed a lichenoid eruption attributed to salazopyrine (Clarke, 1972, 1974). A patient with ulcerative colitis and a lichenoid eruption was described whose rash got worse after withdrawal of salazopyrine (Wilson, 1973). A further patient with ulcerative colitis, lichen planus and myasthenia gravis is on record, together with extensive immunological studies (Miller, 1971). In each ofthe following cases of ulcerative colitis, salazopyrine appears not to have been involved in the genesis of an eruption closely resembling classical lichen planus. CASE REPORTS
i.J.E. male, aged 36 years, a chicken farmer, began to complain of diarrhoea at the end of 1969. At approximately the same time and before any therapy was given he noticed a non-pruritic rash occurring patchily on different parts of the body, particularly prominent on the medial aspects of his forearms. Sigmoidoscopy showed pus, contact bleeding and a variable vascular pattern. Ulcerative colitis was demonstrated radiographically in the distal part of the transverse colon and in the whole ofthe descending colon. His haemoglobin was 11-9 g % with a white blood cell count of 6000/ mm^, the polymorphs showing toxic granulation. Serum mucoprotein was 354 mg/ioo ml. He was treated with salazopyrine, methyl cellulose and prednisolone enemas with reasonable control of his bowel symptoms. However, the eruption became gradually more prominent. When referred for dermatological opinion in April 1972, multiple purple polygonal papules with Wickham's striae were present on his forearms and mid-back. A few mouth lesions of lichen planus were seen. Skin histology was non-specific. A good response was obtained to topical fluocinolone acetonide 0-2% creani. He shortly moved to a different district and has been lost to follow up. 2. W.R. male, aged 45 years, a police inspector, developed a bhstering, itchy eruption on the hands and wrists in June 1973. Three days later he began to get diarrhoea with blood, mucus and abdominal pain. Sigmoidoscopy showed a granular and friable mucosa. Rectal histology showed an increased number of chronic inflammatory cells in the lamina propria, a few glands containing polymorpho465
466
E.H.Wyatt
nuclear exudate in their lumina. Barium enema showed a redundant loop of sigmoid colon and one area of the rectum did not distend well but there was no definite mucosal abnormality. The haemoglobin was 15-9 g% and there was a white blood cell count of 12,000/mm^. The serum mucoprotein was 168 mg/ioo ml. He responded to prednisolone enemas and methyl cellulose. Since then he has had intermittent diarrhoea. Further sigmoidoscopy in January 1974 showed a granular mucosa but no definite inflammatory change. Two months after the onset of the bowel trouble a dermatological opinion was requested and he showed widespread classical lichen planus of his limbs and trimk wi± no evident mucous membrane involvement. Many ofthe lesions on the lower limbs were bullous. Skin histology showed: 'a little hyperkeratosis and epidermal hyperplasia. There is some splitting of the epidermis from the dermis with the formation of a subepidermal bulla. In the upper dermis there is a band-like infiltration of inflammatory cells composed mainly of lymphocytes and polymorphs. The picture is suggestive of bullous lichen planus.' Treatment was carried out with fluclorolone acetonide 0-025% cream under polythene cover, a gradual improvement occurred, and i year later the eruption had settled. . female, aged 51 years, a housewife, started to have diarrhoea in January 1970. Sigmoidoscopy in February 1970 was normal but a barium enema in March 1970 showed a loss of haustration. The haemoglobin was 13 g% with a white cell count of 6000/mm^ and an E.S.R. of 45 mm/h. The serum mucoprotein was 177 mg/ioo ml. She was treated with a short course of systemic steroids and oral salazopyrine. On this regime her symptoms gradually settled down and when diarrhoea occurred, it was easily controlled with methyl cellulose, codeine phosphate and alginates. By the spring of 1971 she had formed stools and was off specific therapy. A repeat barium enema in November 1971 showed definite colitis ofthe descending and sigmoid colon. In January 1972 the diarrhoea became more prominent. Sigmoidoscopy showed a general slight abnormality with a red granular mucosa. In some places the vessel pattern was visible but there was no friability on swabbing. Rectal biopsy showed surface ulceration and considerable chronic infiammatory change extending into the muscle. The submucosa was oedematous and showed some fibrosis. No biochemical evidence of malabsorption was found. Diarrhoea recurred in January 1974, a barium enema showing further loss of haustration and of mucosal pattern indicating progress of ulcerative colitis. In May 1973 she began to get an irritable skin eruption which started on the wrists and then spread to the feet. It was 2 years since she had taken salazopyrine. In view of further spread she was referred for dermatological opinion in September 1973 when she showed classical lichen planus ofthe trunk, limbs, lips and mouth. Skin histology showed: 'The epidermis shows fairly marked hyperkeratosis, a prominent stratum granulosum, acanthosis, and elongation of the rete ridges several of which show saw toothing. In some areas there is degeneration of the basal layer. A fairly dense infiltrate which consists mainly of lymphocytes is present in the upper dermis.' Topical treatment with fiucortolone acetonide 0-025% cream, partly under polythene cover, was associated with gradual fading ofthe rash over the following 15 months. DISCUSSION
Ulcerative colitis and lichen planus are both diseases of unknown aetiology in which immimological processes play a part. Neither is a rare disease; the concurrence of the two conditions in the same patient might sometimes be expected by chance. Simultaneous onset of gut and skin symptoms in two of our patients poses the question of a common factor. Lichen planus frequently affects ± e oral mucous membrane and sometimes the genital mucous membrane. There are single case reports of involvement of the stomach (Milian & Perin, 1936)
Lichen planus and ulcerative colitis
467
and the bladder (Young, 1940) but the evidence for the diagnosis was in both cases circumstantial. No firm evidence exists therefore for recognizing lichen planus in structures of endodermal origin. Johnson & Wilson (1969) reviewed 415 ulcerative colitis patients and found twenty of them to have skin conditions thought to be associated with the underlying bowel disease. Several patients had more than one type of cutaneous lesion. Eight women had erythema nodosum appearing with exacerbations of the colitis; seven patients had pyoderma gangrenosum, apparently unrelated to the severity of the colitis; five patients developed small erythematous papules which broke down to form ulcers; three patients had ulcerating erythematous plaques on the shins. There were no cases of lichen planus (Wilson, 1974). Abnormal glucose tolerance has been confirmed in lichen planus, suggesting a widespread metabolic disturbance (Powell et al, 1974). In lichen planus an erosive process affects generative basal cells which are continuously replaced by the migration of epidermal cells from nearby (Marks, Black & Wilson Jones, 1973). Colloid bodies are formed by fibrillar transformation of basal cells; a band-like upper dermal infiltrate consists mostly of lymphocytes. Complement, fibrin and immunoglobulins IgG, IgM and IgA are demonstrated in this zone (Baart de la Faille-Kuyper & Baart de la Faille, 1974). A review of the aetiology of lichen planus recently appeared in the British Medical Journal (1974). Lumb & Prothero (1957) suggested an intrinsic defect in epithelial regeneration in ulcerative colitis. The earliest lesion would appear to be an inflammatory process in the mucosal crypt where epithelial cells form vacuoles and die, leaving tiny crypt ulcers (Sleisenger & Fordtran, 1973). At first polymorphs are associated with the degenerative epithelial cells but later a chronic infiammatory infiltrate develops consisting of small round cells with a mixture of eosinophils and mast cells. In ulcerative colitis the continuing inflammatory process in the mucosa and submucosa is associated with a thirty-fold increase in mucosal IgG immimocytes, whose function appears to mediate continuing mucosal damage, although IgA and IgM production and transport occur normally (Brandtzaeg et al, 1974). Jewell (1973) has reviewed recent work on the aetiology of ulcerative colitis. To three previously described cases (Miller, 1971; Clarke, 1972; Wilson, 1973) of lichen planus and ulcerative colitis we add three personal cases of the concurrence of the two diseases, in each of which the suggestion of drug induced skin disease due to therapy of the colitis seems to be ruled out. In two of our cases the rash started at the same time as the first bowel symptoms. There are resemblances between the pathology of these two diseases in both of which it appears that epithelial cell turnover may be diminished and individual cell death (apoptosis) occurs followed by a small round cell infiltrate closely appUed to the basement membrane, with immunological disturbance. The skin and gut changes in these patients could therefore have a causal rather than a fortuitous relationship. ACKNOWLEDGMENTS
Thanks are due to Dr John Bennett who referred the patients and to Dr Janet Marks for reading the manuscript. REFERENCES ANNOTATION (1974) Lichen planus—some progress. British Medical Journal, iii, 643. BAART DE LA FAILLE-KUYPER, E.H. & BAART DE LA FAILLE, H . (1974) An immunofluorescence study of lichen
planus. British Journal of Dermatology, 90, 365. BRANDTZAEG, P., BAKLIEN, K . , FAUSA, O . & HOEL, P.S. C1974) Immuno- histo- chemical characterization of
local immunoglobulin formation in ulcerative colitis. Gastroenterology, 66, 1123. CLARKE, G.H.V. (1972) North of England Dermatological Society Clinical Meeting, Manchester (Case No. 4). CLARKE, G.H.V. (1974) Personal communication.
468
E.H.Wyatt
JEWELL, D.P. (1973) Aetiology of ulcerative colitis. Proceedings of the Royal Society of Medicine, 66, 1031. JOHNSON, M.L. & WILSON, H.T.H. (1969) Skin lesions in ulcerative colitis. Gut, 10, 255. LUMB, G.R. & PROTHERO, R.H.B. (1957) The early lesions of ulcerative colitis. Gastroenterology, 33, 457. MARKS, R . , BLACK, M . & WILSON JONES, E . (1973) Epidermal cell kinetics in lichen planus. British Journal of Dermatology, 88, 37. MILIAN & P'RIN, L . (1936) Lichen plan gastrique. Bulletin de la Societe franfaise de dermatologie et de Syphiligraphie, 43, 644. MILLER, T.N. (1971) Myasthenia gravis, ulcerative colitis and lichen planus. Proceedings of the Royal Society of Medicine, 64, 807. POWELL, S.M., ELLIS, J.P., RYAN, T.J. & VICKERS, H.R. (1974) Glucose tolerance in lichen planus. British Journal of Dermatology, 91, 73. SLEISENGER, M.H. & FORDTRAN, J.S. (1973) Gastro-intestinal Disease, p. 1300. Saunders, London. WILSON, H.T.H. (1973) In: Skin manifestations in ulcerative colitis. The Skin and General Medicine (Ed. by J.N.Agate), p. 8. Modern Medicine of Great Britain Ltd, London. WILSON, H.T.H. (1974) Personal communication. YOUNG, E.L. (1940) Lichen planus in the hlzddet. Journal of Urology, 43, 265.
Case Report
Lichen planus and ulcerative colitis EDWARD H.WYATT Department of Dermatology, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ Accepted for publication 24 January 1975
SUMMARY
Three patients with ulcerative colitis and lichen planus are reported and similar cases in the literature discussed. Similarities in the pathology of the two conditions are outlined.
Ulcerative colitis patients have been seen who developed a lichenoid eruption attributed to salazopyrine (Clarke, 1972, 1974). A patient with ulcerative colitis and a lichenoid eruption was described whose rash got worse after withdrawal of salazopyrine (Wilson, 1973). A further patient with ulcerative colitis, lichen planus and myasthenia gravis is on record, together with extensive immunological studies (Miller, 1971). In each ofthe following cases of ulcerative colitis, salazopyrine appears not to have been involved in the genesis of an eruption closely resembling classical lichen planus. CASE REPORTS
i.J.E. male, aged 36 years, a chicken farmer, began to complain of diarrhoea at the end of 1969. At approximately the same time and before any therapy was given he noticed a non-pruritic rash occurring patchily on different parts of the body, particularly prominent on the medial aspects of his forearms. Sigmoidoscopy showed pus, contact bleeding and a variable vascular pattern. Ulcerative colitis was demonstrated radiographically in the distal part of the transverse colon and in the whole ofthe descending colon. His haemoglobin was 11-9 g % with a white blood cell count of 6000/ mm^, the polymorphs showing toxic granulation. Serum mucoprotein was 354 mg/ioo ml. He was treated with salazopyrine, methyl cellulose and prednisolone enemas with reasonable control of his bowel symptoms. However, the eruption became gradually more prominent. When referred for dermatological opinion in April 1972, multiple purple polygonal papules with Wickham's striae were present on his forearms and mid-back. A few mouth lesions of lichen planus were seen. Skin histology was non-specific. A good response was obtained to topical fluocinolone acetonide 0-2% creani. He shortly moved to a different district and has been lost to follow up. 2. W.R. male, aged 45 years, a police inspector, developed a bhstering, itchy eruption on the hands and wrists in June 1973. Three days later he began to get diarrhoea with blood, mucus and abdominal pain. Sigmoidoscopy showed a granular and friable mucosa. Rectal histology showed an increased number of chronic inflammatory cells in the lamina propria, a few glands containing polymorpho465
466
E.H.Wyatt
nuclear exudate in their lumina. Barium enema showed a redundant loop of sigmoid colon and one area of the rectum did not distend well but there was no definite mucosal abnormality. The haemoglobin was 15-9 g% and there was a white blood cell count of 12,000/mm^. The serum mucoprotein was 168 mg/ioo ml. He responded to prednisolone enemas and methyl cellulose. Since then he has had intermittent diarrhoea. Further sigmoidoscopy in January 1974 showed a granular mucosa but no definite inflammatory change. Two months after the onset of the bowel trouble a dermatological opinion was requested and he showed widespread classical lichen planus of his limbs and trimk wi± no evident mucous membrane involvement. Many ofthe lesions on the lower limbs were bullous. Skin histology showed: 'a little hyperkeratosis and epidermal hyperplasia. There is some splitting of the epidermis from the dermis with the formation of a subepidermal bulla. In the upper dermis there is a band-like infiltration of inflammatory cells composed mainly of lymphocytes and polymorphs. The picture is suggestive of bullous lichen planus.' Treatment was carried out with fluclorolone acetonide 0-025% cream under polythene cover, a gradual improvement occurred, and i year later the eruption had settled. . female, aged 51 years, a housewife, started to have diarrhoea in January 1970. Sigmoidoscopy in February 1970 was normal but a barium enema in March 1970 showed a loss of haustration. The haemoglobin was 13 g% with a white cell count of 6000/mm^ and an E.S.R. of 45 mm/h. The serum mucoprotein was 177 mg/ioo ml. She was treated with a short course of systemic steroids and oral salazopyrine. On this regime her symptoms gradually settled down and when diarrhoea occurred, it was easily controlled with methyl cellulose, codeine phosphate and alginates. By the spring of 1971 she had formed stools and was off specific therapy. A repeat barium enema in November 1971 showed definite colitis ofthe descending and sigmoid colon. In January 1972 the diarrhoea became more prominent. Sigmoidoscopy showed a general slight abnormality with a red granular mucosa. In some places the vessel pattern was visible but there was no friability on swabbing. Rectal biopsy showed surface ulceration and considerable chronic infiammatory change extending into the muscle. The submucosa was oedematous and showed some fibrosis. No biochemical evidence of malabsorption was found. Diarrhoea recurred in January 1974, a barium enema showing further loss of haustration and of mucosal pattern indicating progress of ulcerative colitis. In May 1973 she began to get an irritable skin eruption which started on the wrists and then spread to the feet. It was 2 years since she had taken salazopyrine. In view of further spread she was referred for dermatological opinion in September 1973 when she showed classical lichen planus ofthe trunk, limbs, lips and mouth. Skin histology showed: 'The epidermis shows fairly marked hyperkeratosis, a prominent stratum granulosum, acanthosis, and elongation of the rete ridges several of which show saw toothing. In some areas there is degeneration of the basal layer. A fairly dense infiltrate which consists mainly of lymphocytes is present in the upper dermis.' Topical treatment with fiucortolone acetonide 0-025% cream, partly under polythene cover, was associated with gradual fading ofthe rash over the following 15 months. DISCUSSION
Ulcerative colitis and lichen planus are both diseases of unknown aetiology in which immimological processes play a part. Neither is a rare disease; the concurrence of the two conditions in the same patient might sometimes be expected by chance. Simultaneous onset of gut and skin symptoms in two of our patients poses the question of a common factor. Lichen planus frequently affects ± e oral mucous membrane and sometimes the genital mucous membrane. There are single case reports of involvement of the stomach (Milian & Perin, 1936)
Lichen planus and ulcerative colitis
467
and the bladder (Young, 1940) but the evidence for the diagnosis was in both cases circumstantial. No firm evidence exists therefore for recognizing lichen planus in structures of endodermal origin. Johnson & Wilson (1969) reviewed 415 ulcerative colitis patients and found twenty of them to have skin conditions thought to be associated with the underlying bowel disease. Several patients had more than one type of cutaneous lesion. Eight women had erythema nodosum appearing with exacerbations of the colitis; seven patients had pyoderma gangrenosum, apparently unrelated to the severity of the colitis; five patients developed small erythematous papules which broke down to form ulcers; three patients had ulcerating erythematous plaques on the shins. There were no cases of lichen planus (Wilson, 1974). Abnormal glucose tolerance has been confirmed in lichen planus, suggesting a widespread metabolic disturbance (Powell et al, 1974). In lichen planus an erosive process affects generative basal cells which are continuously replaced by the migration of epidermal cells from nearby (Marks, Black & Wilson Jones, 1973). Colloid bodies are formed by fibrillar transformation of basal cells; a band-like upper dermal infiltrate consists mostly of lymphocytes. Complement, fibrin and immunoglobulins IgG, IgM and IgA are demonstrated in this zone (Baart de la Faille-Kuyper & Baart de la Faille, 1974). A review of the aetiology of lichen planus recently appeared in the British Medical Journal (1974). Lumb & Prothero (1957) suggested an intrinsic defect in epithelial regeneration in ulcerative colitis. The earliest lesion would appear to be an inflammatory process in the mucosal crypt where epithelial cells form vacuoles and die, leaving tiny crypt ulcers (Sleisenger & Fordtran, 1973). At first polymorphs are associated with the degenerative epithelial cells but later a chronic infiammatory infiltrate develops consisting of small round cells with a mixture of eosinophils and mast cells. In ulcerative colitis the continuing inflammatory process in the mucosa and submucosa is associated with a thirty-fold increase in mucosal IgG immimocytes, whose function appears to mediate continuing mucosal damage, although IgA and IgM production and transport occur normally (Brandtzaeg et al, 1974). Jewell (1973) has reviewed recent work on the aetiology of ulcerative colitis. To three previously described cases (Miller, 1971; Clarke, 1972; Wilson, 1973) of lichen planus and ulcerative colitis we add three personal cases of the concurrence of the two diseases, in each of which the suggestion of drug induced skin disease due to therapy of the colitis seems to be ruled out. In two of our cases the rash started at the same time as the first bowel symptoms. There are resemblances between the pathology of these two diseases in both of which it appears that epithelial cell turnover may be diminished and individual cell death (apoptosis) occurs followed by a small round cell infiltrate closely appUed to the basement membrane, with immunological disturbance. The skin and gut changes in these patients could therefore have a causal rather than a fortuitous relationship. ACKNOWLEDGMENTS
Thanks are due to Dr John Bennett who referred the patients and to Dr Janet Marks for reading the manuscript. REFERENCES ANNOTATION (1974) Lichen planus—some progress. British Medical Journal, iii, 643. BAART DE LA FAILLE-KUYPER, E.H. & BAART DE LA FAILLE, H . (1974) An immunofluorescence study of lichen
planus. British Journal of Dermatology, 90, 365. BRANDTZAEG, P., BAKLIEN, K . , FAUSA, O . & HOEL, P.S. C1974) Immuno- histo- chemical characterization of
local immunoglobulin formation in ulcerative colitis. Gastroenterology, 66, 1123. CLARKE, G.H.V. (1972) North of England Dermatological Society Clinical Meeting, Manchester (Case No. 4). CLARKE, G.H.V. (1974) Personal communication.
468
E.H.Wyatt
JEWELL, D.P. (1973) Aetiology of ulcerative colitis. Proceedings of the Royal Society of Medicine, 66, 1031. JOHNSON, M.L. & WILSON, H.T.H. (1969) Skin lesions in ulcerative colitis. Gut, 10, 255. LUMB, G.R. & PROTHERO, R.H.B. (1957) The early lesions of ulcerative colitis. Gastroenterology, 33, 457. MARKS, R . , BLACK, M . & WILSON JONES, E . (1973) Epidermal cell kinetics in lichen planus. British Journal of Dermatology, 88, 37. MILIAN & P'RIN, L . (1936) Lichen plan gastrique. Bulletin de la Societe franfaise de dermatologie et de Syphiligraphie, 43, 644. MILLER, T.N. (1971) Myasthenia gravis, ulcerative colitis and lichen planus. Proceedings of the Royal Society of Medicine, 64, 807. POWELL, S.M., ELLIS, J.P., RYAN, T.J. & VICKERS, H.R. (1974) Glucose tolerance in lichen planus. British Journal of Dermatology, 91, 73. SLEISENGER, M.H. & FORDTRAN, J.S. (1973) Gastro-intestinal Disease, p. 1300. Saunders, London. WILSON, H.T.H. (1973) In: Skin manifestations in ulcerative colitis. The Skin and General Medicine (Ed. by J.N.Agate), p. 8. Modern Medicine of Great Britain Ltd, London. WILSON, H.T.H. (1974) Personal communication. YOUNG, E.L. (1940) Lichen planus in the hlzddet. Journal of Urology, 43, 265.
