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Rheumatoid arthritis (RA) or Crohn's disease (CD) are both recognised indications of anti-tumour necrosis factor α treatment, indicating that these diseases may have important mechanisms in common, at least in part, through the contribution of the Th1/Th2 cytokine balance.1-3 The classical improvement of 75% of patients with RA during pregnancy suggests that pregnancy is a natural situation where this balance is modified.4 5 It is thus of interest to describe the clinical course of a patient with the association of two inflammatory diseases, RA and ulcerative colitis (UC) and its modulation by pregnancy.
Rectal bleeding and mild foot arthralgias started in a 36 year old woman with no particular personal or familial history one year before her first pregnancy. These symptoms remained the same until and during pregnancy. Two weeks after a normal delivery, rectal bleeding became more abundant and painful. Acute infectious gastroenteritis was diagnosed and symptomatic treatment was prescribed. After one month and a half there was no improvement, with up to 10–20 watery and bloody stools a day. A coloscopy showed an inflammation of the whole colon consistent with UC. She was treated with mesalazine, 3 g/day, and steroids, 1 mg/kg/day. No improvement was seen and the patient went to hospital for parenteral nutrition. After three weeks there was a major improvement, she had a normal coloscopy and went home.
Two weeks later, she was sent back to the hospital after a major relapse with massive bloody diarrhoea, abdominal pain, and rapid weight loss. Laboratory investigations showed erythrocyte sedimentation rate 32 mm/1st h, C reactive protein 89 mg/l, haemoglobin 90 g/l, leucocytes 12 600/μl, and serum albumin 21 g/l. Despite being treated with steroids intravenously and cyclosporin, with some effect on arthritis, the colitis continued to deteriorate and a total colectomy with ileostomy was performed. Histological analysis of the colon showed a diffuse inflammation of the colon with an infiltration of the mucosa and lamina propria with lymphocytes, plasma cells, and granulocytes.
When first seen for arthritis, she had a very active, distal, and symmetrical arthritis affecting mostly hands and feet, with severe synovitis. She had pain at night and morning stiffness of at least one hour. A Rose-Waaler test was positive 1/128, antinuclear antibody negative, and HLA A3/A24 B7/B38 DRB1*0101/DR14 DQ5. Footx rays showed bilateral erosions of the fifth metatarsophalangeal joints. No sacroiliitis was found and the lumbar spine was normal. Treatment with methotrexate 7.5 mg, then 15 mg/week intramuscularly and salazopyrine 3 g/day associated with calcium, vitamin D, and pamidronate was begun. The treatment was not completely effective.
UC is commonly associated with arthritic manifestations, and differential diagnosis between RA and UC associated arthritis can be difficult. In this patient the diagnosis of RA was made according to the 1987 American Rheumatism Association criteria with a DR1 genotype. The diagnosis of UC was made on the basis of the clinical course, endoscopic findings, and colon pathology. A bibliographic search showed that only a few cases of associations between RA and CD or UC have been described, and the influence of pregnancy on the association of RA and UC has never been seen before.6-9
Here, both RA and UC were poorly active or inactive during pregnancy with a severe postpartum relapse for the two sets of symptoms. Even if we cannot exclude a coincidental association of the two diseases, the simultaneous occurrence of the flare suggests that the underlying mechanisms of inflammation in the two diseases are common. Pregnancy is thought to induce a shift from Th1 to Th2 response, increasing the contribution of anti-inflammatory cytokines.3 Pregnancy has a protective effect on RA, UC, and other Th1 mediated inflammatory diseases which is terminated after delivery. Understanding of the underlying mechanisms may have clinical therapeutic applications in these conditions.
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