Eosinophilic fasciitis and eosinophilic colitis: a rare association

E. Suresh, V. Doherty1, O. Schofield1, C. Goddard2 and V. Dhillon

Rheumatic Diseases Unit, Western General Hospital, Edinburgh, 1 Department of Dermatology and 2 Department of Gastroenterology, St John's Hospital, Livingston, UK

Correspondence to: E. Suresh, Rheumatic Diseases Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. E-mail: dr_esuresh{at}hotmail.com

SIR, Although eosinophilic fasciitis (EF) was originally considered to be a disease predominantly localized to the fascia, several case reports have subsequently reported other manifestations [1–7]. Aplastic anaemia, haemolytic anaemia, thrombocytopenia, lymphoproliferative disorders, thyroiditis, pulmonary fibrosis, Sjögren's syndrome, Raynaud's phenomenon, myositis, medium vessel vasculitis, pericarditis, colitis and glomerulonephritis are some of the manifestations that have been reported in patients with EF. To our knowledge, the association of eosinophilic colitis (EC) and EF has been reported only once before [6]. Here, we describe an additional patient with EF who developed EC.

A 38-yr-old previously fit and healthy man initially presented to the general physicians in December 2000 with a 2-month history of fatigue and generalized myalgia that was worse after exertion. The onset of his illness was acute following several hours of extreme physical exertion at work. He denied any exposure to toxins, drugs or nutritional supplements prior to the onset of his illness. Physical examination was entirely unremarkable at this stage. In particular, he had normal power in all muscle groups. Routine laboratory testing revealed normal values for erythrocyte sedimentation rate, C-reactive protein and creatine kinase, but eosinophil count was elevated at 1.8 x 109/l [normal range (0–0.4) x 109/l]. Over the next several weeks, he developed increasing swelling in his ankles, erythema over his lower legs and restricted range of movements in his wrists and ankles. His skin was then noted to be indurated not only in his lower legs, but also in his forearms. His eosinophil count had steadily risen to 4.8 x 109/l during this time. There were no clinical features suggestive of systemic sclerosis such as sclerodactyly, Raynaud's phenomenon or nailfold capillary abnormalities. Pulmonary function tests and echocardiogram were entirely unremarkable. The relevant serological tests (antinuclear antibody and antibodies to extractable nuclear antigens) were negative.

A presumptive clinical diagnosis of eosinophilic fasciitis (EF) was made by the dermatologist and was confirmed on full thickness skin biopsy (down to superficial muscle) taken from his forearm (Fig. 1). Histological examination of the biopsy specimen showed an inflammatory cell infiltrate, predominantly composed of eosinophils, in the deep subcutaneous tissue and fascia with associated fibrosis. There was patchy, mild perivascular inflammation in the skin, but there was no definite abnormality in the skeletal muscle. The general physicians commenced him on 40 mg of prednisolone/day in May 2001, but it appeared that he did not derive any benefit from it. His eosinophil count fell to less than 0.2 x 109/l even before prednisolone was commenced and he eventually reported subjective improvement in symptoms following intense physiotherapy. This was associated with softening of the affected areas on his limbs. The dose of his prednisolone was rapidly tapered after September 2001 and he was receiving only 5 mg/day when he first came to our attention in October 2001.



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FIG. 1. Histology of deep skin biopsy showing features consistent with eosinophilic fasciitis. There is an inflammatory cell infiltrate in the deep subcutaneous tissue composed of lymphocytes, neutrophils and prominent eosinophils.

 
Soon thereafter, he developed persistent bloody diarrhoea and was referred for specialist gastroenterology opinion. Flexible sigmoidoscopy revealed severe colitis. Colonic biopsy samples showed active inflammatory reaction with focal clusters of eosinophils in lamina propria, consistent with eosinophilic colitis (Fig. 2). No ischaemic or vasculitic features were identified. In view of these findings, the dose of his prednisolone was increased and he was commenced on mesalazine. Cimetidine was also added later in view of anecdotal evidence of improvement in symptoms of EF (see below) [7]. Although there was good initial response with resolution of bowel symptoms with the above measures, he was being maintained on 7 mg of prednisolone/day (with appropriate bone protection) at the time of writing this letter, as his bowel symptoms flared each time the dose was reduced below this level. Methotrexate was being considered as a steroid-sparing agent to control his bowel disease.



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FIG. 2. Histology of colonic biopsy specimen showing features consistent with eosinophilic colitis. The lamina propria contains varying numbers of eosinophilis in focal clusters.

 
Extracutaneous and visceral manifestations are increasingly recognized in patients with EF. Colitis has, however, been reported in such patients only twice, and EC only once. The only other EF patient who developed EC also had multisystem involvement with pericarditis, thyroiditis and monoclonal gammopathy [6]. In the other patient, the features of colitis were considered to be consistent with Crohn's disease [7]. In our patient, EC occurred as an isolated visceral manifestation several months after the diagnosis of EF was made. It is difficult to prove that this association was not coincidental, but it may be possible to speculate that the mechanisms underlying the association are immune mediated. Although the exact immunological mechanisms have not been identified, there is some evidence for the role of T lymphocytes in the causation of EC. In a murine model of oral antigen-induced diarrhoea associated with colonic inflammation, colonic T cells have been shown to transfer the disease to naive mice through a STAT6-dependent mechanism [8]. The occurrence of hypergammaglobulinaemia and inflammatory cell infiltrate in the fascia and the association with autoimmune haematological disorders, Sjögren's syndrome and thyroiditis support the role for immune-mediated mechanisms in the causation of EF. It should also be noted that EC in adults could be secondary to drug reactions and parasitic infections, and toxins such as L-tryptophan [9] and infection by Borrelia burgdorferi [10] have been reported as causative agents in EF.

In view of the rarity of this syndrome, evidence-based management drawn from controlled trials cannot be offered for patients with EF. Removal of the inciting agent (if one is identified) is the most important measure. Prednisolone is often used as most patients show partial or complete response. We, however, did not feel that prednisolone helped the EF component in our patient. Hydroxychloroquine, methotrexate and cimetidine have also been reported to be beneficial, of which the latter was used in our patient. Cimetidine is thought to act through blockage of lymphocyte function and it should be noted that a subpopulation of lymphocytes possesses H2 receptors [11]. In fact, it is believed that lymphocytes (and not eosinophils) play a primary role in the causation of EF. Therapy for EC in our patient was along the lines of inflammatory bowel disease, which is why mesalazine was used and the dose of prednisolone was increased. Again, there are no controlled trials in patients with EC to dictate the correct management.

In conclusion, it is important to appreciate the widening spectrum of EF and carefully look for internal organ involvement. The pathogenesis of the association between EF and EC is unknown, but is possibly immune mediated. Treatment for these conditions is largely based on only anecdotal evidence.

We wish to thank Dr Ronald Davie, Consultant Histopathologist, Department of Pathology, St John's Hospital, Livingston, UK for his help with the preparation of the images.

The authors have declared no conflicts of interest.

References

  1. Doyle JA and Ginsburg WW. Eosinophilic fasciitis. Med Clin North Am 1989;73:1157–66.[ISI][Medline]
  2. Kaplinsky N, Revach M, Katz W. Eosinophilic fasciitis: report of a case with features of connective tissue disease. J Rheumatol 1980;7:536–40.[ISI][Medline]
  3. Smiley AM, Husain M, Indenbaum S. Eosinophilic fasciitis in association with thyroid disease: a report of three cases. J Rheumatol 1980;7:871–6.[ISI][Medline]
  4. Janzen L, Jeffrey JR, Gough J, Chalmers IM. Response to methotrexate in a patient with idiopathic eosinophilic fasciitis, morphea, IgM hypergammaglobulinemia and renal involvement. J Rheumatol 1995;22:1967–70.[ISI][Medline]
  5. Song YW, Kim HA, Song KY. Eosinophilic fasciitis with occlusive vasculitis and gangrene of the finger. J Rheumatol 1995;22:356–9.[ISI][Medline]
  6. Naschitz JE, Yeshurun D, Miselevich I, Boss JH. Colitis and pericarditis in a patient with eosinophilic fasciitis. A contribution to the multisystem nature of eosinophilic fasciitis. J Rheumatol 1989;16:688–92.[ISI][Medline]
  7. Martin JR, Williams JP, Barrowman JA. Diffuse Eosinophilic fasciitis, atypical rash and chronic inflammatory disease of the colon Crohn's disease. J Rheumatol 1980;7:928–9.[ISI][Medline]
  8. Kweon MN, Yamamoto M, Kajiki M, Takahashi I, Kiyono H. Systemically derived large intestinal CD4(+) Th2 cells play a central role in STAT-6 mediated allergic diarrhoea. J Clin Invest 2000;106:199–206.[Abstract/Free Full Text]
  9. Martin RW, Duffy J, Lie JT. Eosinophilic fasciitis associated with the use of L-tryptophan: a case-control study and comparison of clinical and histopathological features. Mayo Clin Proc 1991;66:892–8.[ISI][Medline]
  10. Hashimoto Y, Takahashi H, Matsuo S, et al. Polymerase chain reaction of Borrelia burgdorferi flagellin gene in Shulman syndrome. Dermatology 1996;192:136–9.[ISI][Medline]
  11. Solomon G, Barland P, Rifkin H. Eosinophilic fasciitis responsive to cimetidine. Ann Intern Med 1982;97:547–9.[ISI][Medline]
Accepted 5 November 2004





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