Dermatomyositis–scleroderma overlap syndrome presenting as autoimmune haemolytic anaemia

J. Andrews and M. A. Hall

Department of Rheumatology, Wexham Park Hospital, Slough SL2 4HL, UK

SIR, We report a case of dermatomyositis–scleroderma overlap syndrome presenting with autoimmune haemolytic anaemia. A 41-yr-old Caucasian woman was refer red to the Department of Haematology in January 1998 from her general practitioner with a haemoglobin of 6 g/dl (normal range 11.5–16.5) and a 6-month history of lethargy, night sweats and recurrent oral ulceration. In addition, she had experienced arthralgia for the last 6 yr, which had responded dramatically to NSAID, and also described Raynaud's phenomenon and dysphagia of solids. She was found to have Coombs-positive autoimmune haemolytic anaemia and was commenced on 1 mg/kg oral prednisolone with little effect, requiring multiple blood transfusions. Azathioprine was introduced but had to be discontinued due to hepatic dysfunction. She underwent splenectomy in May of the same year and following this, was able to reduce her prednisolone dose to 15 mg/day.

Her arthralgia had improved with high-dose steroids but recurred during the period of steroid reduction. When referred to the Department of Rheumatology in February 1999, we found her to have moderate symmetrical proximal muscle weakness, widespread large and small joint synovitis, a heliotrope facial rash, Gottron's papules, ‘mechanic's hands’ (Fig. 1AGo and B) and a 10 cm by 20 cm area of thickened, indurated skin on the lateral aspect of her right thigh. Various investigations were performed: renal, liver and thyroid function were normal, haemoglobin 10.4 g/dl, white cell count 29.2 x 109/l (normal range 4.0–11.0) and platelets 660 x 109/l (normal range 150–400) in keeping with her post-splenectomy state. Total creatine kinase was 994 IU/l (normal range 24–204), lactate dehydrogenase 427 IU/l (normal range 135–225). An autoantibody screen was negative except for the presence of antibodies to Jo-1. Serum immunoglobulins and complement levels were normal and cryoglobulins were not detected. X-rays of the hands showed amorphous calcification along the lateral border of the right hand. Pulmonary function tests revealed a restrictive defect with mildly impaired gas transfer; chest X-ray and echocardiogram were normal. Muscle biopsy confirmed an inflammatory myopathy. A barium swallow reported changes consistent with a diagnosis of scleroderma (dilated distal oesophagus with reduced peristaltic waves).



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FIG. 1.  Mechanic's hands.

 
A diagnosis of dermatomyositis–scleroderma overlap syndrome was made. She was commenced on oral metho trexate but developed a rash and severe breathlessness that resolved on cessation of the drug. Cyclosporin (225 mg/day) was added to her prednisolone therapy, and she responded well over the next year with her creatine kinase returning to the normal range (98 IU/l) and some, but not complete, improvement in muscle power. However, in May 2000, she re-presented with marked myalgia, increasing calcinosis of her hands and an elevated total creatine kinase once more (254 IU/l). She was commenced on intravenous immuno globulin 1 g/kg for 2 days each month and initially showed some improvement, before relapsing once again after 3 months of treatment. We have now commenced her on pulsed intravenous cyclophosphamide and methylprednisolone therapy for her severe, resistant disease.

Autoimmune haemolytic anaemia is a well recognized associated finding in some connective tissue disorders such as SLE or RA, but it rarely occurs in association with dermatomyositis [1]. To our knowledge, this is the first reported case of dermatomyositis–scleroderma overlap syndrome presenting with autoimmune haemolytic anaemia. Our patient had all but electromyographic confirmation of dermatomyositis using the standard Bohan and Peter diagnostic criteria [2]. Of all the connective tissue diseases, dermatomyositis most commonly overlaps with scleroderma and our patient fulfilled the criteria for this diagnosis to be made [3].

Anti-nuclear antibodies are present in 60–80% of patients with inflammatory myopathies, 50% of these autoantibodies are specifically associated with muscle disorders [myositis-specific autoantibodies (MSAs)]. The most common of these is the anti-synthetase antibody: anti-histidyl-tRNA antibody (or Jo-1 antibody) which is associated with a syndrome of more extensive disease (interstitial lung disease, polyarth ritis—particularly affecting the small joints of the hands, Raynaud's phenomenon and ‘mechanic's hands’—cracked, fissured, hypertrophic changes over the distal fingers). Other MSAs are: anti-SRP antibody (associated with severe myopathy, the absence of a rash and a poor response to therapy), anti-Mi-2 antibody (associated with the classical rash, a relatively benign course and a good response to therapy), and also anti- PL-7, anti-PL-12, anti-EJ and anti-OJ antibodies.

The mainstay of treatment of dermatomyositis is oral corticosteroids, however, up to 25% of patients will show a poor response to this alone. Azathioprine, and increasingly commonly methotrexate (as single agents or in combination), are widely used in patients who fail to respond to corticosteroid therapy. Other immunosuppressants used include cyclosporin or intravenous cyclophosphamide, although there are few controlled trials to support their use in myositis. In resistant cases, high-dose intravenous immunoglobulin has been shown to be of benefit in patients who have not responded to other treatments [4]. Its long-term efficacy is not known and its high cost limits widespread use. Calcium channel blockers (diltiazem) and warfarin have shown some potential in the treatment of calcinosis in inflammatory myopathies [5, 6]. However, as yet there is no conclusive evidence of a useful treatment effect. To our knowledge, this is the first reported case of dermatomyositis–scleroderma overlap syndrome presenting as auto immune haemolytic anaemia. In keeping with previous reports of patients with Jo-1-positive dermatomyositis, our patient has responded poorly to a number of first and second line therapies and has extensive disease that is proving difficult to control.

Notes

Correspondence to: J. Andrews. Back

References

  1. Hardman CM, Garioch JJ, Leonard JN, Ozanne C, Abdalla SH. Autoimmune haemolytic anaemia associated with dermatomyositis. Clin Exp Dermatol1996;21:437–9.[ISI][Medline]
  2. Bohan A, Peter J. Polymyositis and dermatomyositis. N Engl J Med1975;292:344–7.[ISI][Medline]
  3. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum1980; 23:581– 90.[ISI][Medline]
  4. Dalakas MC, Illa I, Dambrosia JM, Soueidan SA, Stein DP, Otero C, Dinsmore ST, McCrosky S. A controlled trial of high-dose intravenous immune globulin transfusions as treatment for dermatomyositis. N Engl J Med1993;329:1193–2000.[Free Full Text]
  5. Oliveri MB, Palermo R, Mautalen C, Hubscher O. Regression of calcinosis during diltiazem treatment in juvenile dermatomyositis. J Rheumatol1996;23:2152–5.[ISI][Medline]
  6. Matsuoka Y, Miyajima S, Okada N. A case of calcinosis universalis successfully treated with low-dose warfarin. J Dermatol1998; 25:716–20.[Medline]
Accepted 7 March 2002





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