Clinical Quiz (2006)

A six-week-old male presented with a one week history of bloody diarrhea. His weight was 4410 g (25th percentile). On admission he had a mild normochromic anemia with a hemoglobin concentration of 7.3 g/dL and a mean corpuscular volume of 93 fl. The platelet count and coagulation studies were normal. With the diagnosis of an acute gastrointestinal bleed the boy was transfused. While esophagogastroduodenoscopy did not show any abnormalities, colonoscopy revealed colitis with multiple areas of inflamed mucosa and an ulcerated lesion in the rectum. The histologic picture of the colon mucosa was consistent with an erosive colitis and cryptitis (Fig. 1). On immunohistochemistry a focal infiltration by a CD68+ cell population with an increased Ki67+ growth fraction was seen in the erosive lesions (Fig. 2). On a follow-up visit, five weeks after colonoscopy, a dry erythematous skin lesion was noticed in the axillary folds (Fig. 3).FIG. 1: Sigmoid biopsy with features of an erosive colitis and cryptitis (hematoxylin and eosin; magnification ×10).FIG. 2: Sheets of histiocytic cells with an increased Ki67+ labelling index in the lamina propria of the sigmoid mucosa (magnification ×63).FIG. 3: Dry erythematous skin lesion in the axillary folds on a follow-up visit 5 weeks after chemotherapy.What is the correct diagnosis? Food induced colitis (allergic colitis) Langerhans' cell histiocytosis Infectious colitis Crohn's disease Hemolytic-uremic syndrome ANSWER/DISCUSSION Immunohistochemistry on a skin biopsy specimen revealed an accumulation of histiocytes coexpressing CD1a and S-100 (Fig. 4). Therefore, the diagnosis of Langerhans' cell histiocytosis (LCH) was made. Additional staining showed that the histiocytic cells in the colonic biopsy specimen were also positive for these antigens (Fig. 5). The child was treated with steroids and vinblastine, according to the protocol of the LCH-III Study, with rapid improvement of gastrointestinal symptoms.FIG. 4: Skin biopsy, CD1a stain, shows strong positivity in foci of Langerhans'cells magnification (×10).FIG. 5: Sigmoid biopsy, CD1a stain, demonstrates immunolabling of histiocytic cells consistent with Langerhans' cell histiocytosis (magnification ×63).LCH is a rare disease originating primarily from the proliferation of antigen-presenting dendritic cells. The disorder can involve many different organ systems with the skin and bones most commonly affected. The diagnosis is made by immunohistochemistry demonstrating CD1a- and S100-expressing histiocytic cells (1). Prognosis for patients with localized disease is excellent independent of treatment. In patients with multisystem disease chemotherapy with Prednisone and Vinblastin, it leads to an overall probability of survival of around 80% (2). Involvement of the small and large bowel is reported in < 5% of patients (3,4). In case of bowel-disease the ileum is most commonly affected with clinical signs like vomiting, protein loosing enteropathy, malabsorption, and diarrhea. If the colon is involved, bloody diarrhea is the leading symptom (5). The incidence of gastrointestinal involvement in LCH is unknown. There are only case reports in the literature (3). Due to the unspecific gastrointestinal symptoms only few children undergo endoscopy and therefore bowel-involvement can not be proven histologically. It is assumed that the incidence is much higher as described so far (3). In a retrospective study, 5 of 275 children with LCH had colon involvement proven by histology (3). None of these children had gastrointestinal symptoms initially and the diagnosis of LCH had been made before on an extracolic site (3). This case report demonstrates that LCH may initially present with symptoms and signs of colonic involvement even without extraintestinal symptoms. We conclude that in a condition of colitis of primarily unknown origin the differential diagnosis of Langerhans' cell histiocytosis should be taken into consideration, and other organ systems, especially the skin, should be carefully examined.