Vitiligo and Crohn's Disease in Children

Inflammatory bowel disease (IBD) is associated with several extraintestinal manifestations involving skin, joints, and other organs (1). Erythema nodosum and pyoderma gangrenosum are the common skin manifestations, although there is a long list of other skin disorders associated with IBD (1). Vitiligo is a depigmentation skin disorder presumed to be of autoimmune origin. There are a few single case reports of vitiligo in association with ulcerative colitis (2,3) and Crohn's disease (4) in adults. To the best of our knowledge, there is only a single case report of vitiligo in association with Crohn's disease in children (5). In a recent extensive review of extraintestinal manifestations of IBD in children, vitiligo was not reported (1). We report four children with vitiligo and Crohn's disease seen during a 9-year period. CASE REPORTS From 1988 through 1996, Crohn's disease was diagnosed in 180 children at British Columbia's Children's Hospital. Vitiligo was observed in four of these children at the ages of 2, 7, 7, and 15 years. Patient 1 In a 2-year-old boy of East Indian background, depigmented patches developed on the right side of the back, upper arm, and axilla. Segmental vitiligo was diagnosed, and he was treated with a topical steroid preparation. There was a moderate response to treatment with some repigmentation. At the age of 4.6 years, he was brought to the gastroenterology clinic with a history of bloody diarrhea of 6 months' duration. His father had a history of "colitis" but no more details were available. Examination revealed patches of vitiligo on the right axilla, back, and medial upper arm. Other systemic examination was unremarkable. Blood tests showed hemoglobin, 10.4 g/dl; mean corpuscular volume (MCV), 75 fl; total proteins, 5.1 g/dl; albumin, 3.4 g/dl; and negative antinuclear antibody titers. Colonoscopy showed pancolitis with histology compatible with the diagnosis of inflammatory bowel disease. The gastrointestinal symptoms responded well to 5-aminosalicylic acid (ASA-Asacol; Proctor & Gamble Pharmaceuticals, Toronto, Canada) and systemic steroid treatment. At the age of 6 years, the patient had abdominal pain and weight loss without diarrhea. The small bowel appeared normal on barium follow-through study. Upper gastrointestinal endoscopy showed aphthous ulcers in the stomach and the duodenum with chronic inflammation on the histologic analysis. Based on these findings and the history, Crohn's disease was diagnosed. He responded well to a short course of systemic steroid therapy. He continues to do well at the age of 7 years and is in remission with a maintenance regimen of Asacol. The vitiligo patches have not progressed. Patient 2 An 8.5-year-old white boy had a 6-month history of diarrhea and weight loss. His mother had Crohn's disease. On examination he had depigmented white patches on the left side of the head and face along with depigmentation of scalp hair. These were first noticed when he was 7 years of age. The remainder of the examination was unremarkable. Blood tests showed hemoglobin, 12.6 g/dl; MCV, 75 fl; erythrocyte sedimentation rate, 35 mm/hour; total proteins, 6.6 g/dl; albumin 3.5 g/dl; negative antithyroid antibody titers, and positive antinuclear antibody titers (1:160). Colonoscopy showed aphthous ulcers in the left colon and the terminal ileum with skip lesions. Barium small bowel follow-through study showed disease in the ileum and colon. Based on the disease distribution and the presence of granuloma on histologic analysis, Crohn's disease was diagnosed. Therapy with a 5-ASA preparation (Salofalk; Axan Pharma, Mont. St-Hilaire, Canada) and oral steroids was initiated, and the disease went into remission. In the dermatology clinic, segmental vitiligo was treated with topical steroids, producing some improvement. The Crohn's disease is in remission with the patient aged 9 years. Patient 3 A 10-year-old boy of East Indian background had had intermittent bloody diarrhea and weight loss for approximately 2 years. On examination he had depigmented white patches over the right side of the chest, knee, genitalia, and perioral area. The depigmentation was noticed initially when he was 7 years of age. Other examination was unremarkable except for pallor. Blood tests showed hemoglobin, 10.2 g/dl; MCV, 70 fl; sedimentation rate, 18 mm/hour; total proteins, 6.1 g/dl; albumin, 3.3 g/dl; and negative antithyroid antibody and antinuclear antibody titers. Colonoscopy showed erythema and ulcers of the colonic mucosa and histologic study showed crypt abscesses and aggregates of multinucleated cells without definite granuloma. Crohn's disease was diagnosed, and the patient responded well to 5-ASA (Asacol) and steroid treatment. Segmental vitiligo was confirmed in the dermatology clinic. Topical steroid treatment was initiated, but there was no significant improvement. At the age of 12 years, he received topical psoralen and ultraviolet light A therapy for extensive and progressive vitiligo with a good response. Except for one mild relapse of Crohn's disease, he continues to do well at the age of 19 years. Patient 4 A 15.5 year-old white boy had had intermittent diarrhea and weight loss for 1 year. Approximately 4 months before the onset of these symptoms, he noted pale white patches on the right side of his neck and face. On examination, he looked unwell with pallor, peripheral edema, and small vitiligo patches on his neck and face. Abdominal and other systemic examinations were unremarkable. Investigations showed hemoglobin, 9.3 g/dl; MCV, 99 fl; total proteins, 3.6 g/dl; and albumin, 1.0 g/dl. Endoscopy showed ulcerations and erythema in the colon, terminal ileum, stomach, and duodenum, with granulomatous inflammation observed in histologic analysis. Barium contrast study and follow-through showed disease in jejunum, ileum, and colon. Crohn's disease was diagnosed, and therapy with a 5-ASA preparation (Pentasa; Hoechst Marion Roussel, Laval, Canada) and oral steroids was initiated. Segmental vitiligo was confirmed in the dermatology clinic, and treatment with sunscreens was advised. Because of frequent relapses of Crohn's disease and growth retardation, 6-mercaptopurine and an elemental diet were prescribed, and the symptoms improved. The vitiligo has not progressed and remains limited to his face and neck. None of these four children had a history of another major medical illness or autoimmune disorder. There was no family history of vitiligo in any of the four patients. Patients 1, 2, and 3 had few relapses of Crohn's disease, which responded well to standard therapy; and patient 4 had multiple relapses, requiring steroids and 6-mercaptopurine treatment. Vitiligo was stable in all patients except patient 3 who required psoralen and ultraviolet A light therapy for progressive vitiligo. There was no obvious correlation in the course or severity of vitiligo and Crohn's disease. The course of vitiligo was not affected by oral steroids or 6-mercaptopurine, used for the management of Crohn's disease. DISCUSSION Vitiligo is an acquired skin disorder characterized by a loss of cutaneous pigment due to destruction of melanocytes. Vitiligo affects all races and sexes equally and occurs in approximately 0.5% to 1% of the general population (6,7). Approximately 30% to 40% of vitiligo patients have a positive family history of the condition (6). The diagnosis is clinical, and there is an increased incidence of organ-specific serum autoantibodies associated with vitiligo. The course is usually progressive, and the response to treatment is variable. The treatment consists of sunscreens, topical steroids, and psoralen and ultraviolet A light therapy which is used in patients aged more than 12 years (6). Childhood vitiligo is considered to be a subset of vitiligo characterized by a higher incidence of segmental presentation involving a dermatomal or quasidermatomal distribution and strong autoimmune disease background (8). Crohn's disease is a chronic, transmural, inflammatory process involving any segment of the gastrointestinal tract from mouth to anus. There are a variety of cutaneous manifestations of Crohn's disease. In one series, 15% of adult patients with Crohn's disease were reported to have an associated specific skin disorder (9). Cutaneous disorders described in children with Crohn's disease include erythema nodosum, pyoderma gangrenosum, psoriasis, metastatic cutaneous Crohn's disease, erythema elevatum diutinum, and cutaneous polyarteritis nodosa (1). Vitiligo has been reported rarely in association with Crohn's disease. In a review of the literature we found only two case reports of this association. A single pediatric report described a 14-year-old boy with almost simultaneous onset of vitiligo and regional enteritis without colonic involvement (5). Another case report described a 30-year-old woman in whom progression of preexistent vitiligo patches was noted with the onset of Crohn's colitis (4). Vitiligo has also been noted in a series of adult patients with inflammatory bowel disease, but these studies contain no specific discussion of the association (10,11). Snook et al. (10) reported vitiligo in 1.1% of adults with ulcerative colitis and 0.5% of patients with Crohn's disease compared with 0.3% in a control population. McCallum and Kinmont (11) noted vitiligo in 3 of 138 adults (2.2%) with Crohn's disease (11). Using population-based studies and medical records, it has been estimated that the prevalence of vitiligo in the world's population is 0.5% to 1% (6,7). A population-based study from India suggests the prevalence of 0.2% in that population (12). Although approximately half of patients with vitiligo have development of skin lesions before 20 years of age, only 25% of patients have vitiligo before the age of 8 years (6). If the higher prevalence of 1% is accepted for the general population, the prevalence of vitiligo in children less than 20 years of age is 0.5%; in patients aged less than 8 years of age it is only 0.25%. In our population of children up to 17 years of age with Crohn's disease, the prevalence of vitiligo was 2.2% (4 of 180). We had 30 children with Crohn's disease diagnosed before the age of 8 years, and therefore the prevalence of vitiligo in that subpopulation was 10% (3 of 30). Therefore, it appears that vitiligo occurs at a higher rate in children with Crohn's disease than in the general population. Our patients with vitiligo and Crohn's disease had several unique features. They were all boys, whereas in the general population vitiligo has an equal sex distribution (6). Three of the four children were aged less than 8 years, an age group in which the incidence of vitiligo or Crohn's disease alone is much lower. All our patients had segmental vitiligo, whereas this clinical type was reported in only 19% of the children with vitiligo (8). All four children had colonic involvement of Crohn's disease, and vitiligo preceded the gastrointestinal symptoms in all patients. One of three patients had positive autoantibody titers (33%) compared with 18% of children with vitiligo in a pediatric series (8). The exact pathogenesis of the skin manifestations associated with IBD or Crohn's disease remains unknown, but immunologic mechanisms have been suspected (1). McPoland and Moss (4) have speculated that suppressor T-cell inhibition during active Crohn's disease may lead to increased humoral antimelanocytic activity, leading to worsening of vitiligo (4). Another possible mechanism is based on the detection of a shared and unique epitope on human colon, skin, and biliary epithelium. It has been proposed that autoimmunity directed against this epitope may be a link to the dermatologic and biliary complications of ulcerative colitis (13). This theory may also explain the increased incidence of skin manifestations when the colon is involved in Crohn's disease (23% in colitis compared with 9% in regional enteritis) (8) It is also possible that vitiligo and Crohn's disease have a common genetic predisposition. However there is a marked genetic heterogeneity in both conditions, and genetic markers for both conditions must be better characterized to allow further comment on the possible genetic link between vitiligo and Crohn's disease. In summary, we present four young boys with vitiligo preceding Crohn's disease. The unique features in these children suggest a possible association between the two conditions. The possibility of Crohn's disease should be considered in patients with vitiligo and gastrointestinal symptoms.