pyoderma gangrenosum and myelodysplasia

Clin. lab. Haemat. 1987, 9, 425-428

CASE REPORT

Pyoderma gangrenosum and myelodysplasia

P. YATES*, MRCP, G. CORBETTT, MRCP, & G. STOCKDILLS, F R C P , MRCPath *Department of Haematology, Southmead Hospital, Bristol ?Department of Haematology, Western General Hospital, Edinburgh and j: Department of Haematology, Peel Hospital, Galashiels

Accepted for publication 12 February 1987

Summary Pyoderma gangrenosum has been recognized occurring in association with acute and chronic leukaemia. More recently it has been described in patients with myelodysplasia (Jacobs, Palmer & Gordon-Smith 1985). We report a case of pyoderma gangrenosum in a patient with a preceding history of myelodysplasia, illustrating the problem of controlling the skin disease in this condition and the eventual transformation of the myelodysplasia into acute leukaemia. Treatment of the leukaemia resulted in improvement of the skin lesions.

Keywords: pyoderma gangrenosum, myelodysplasia, acute myeloid leukaemia

Case report

A 54-year-old man presented in October 1984 with pancytopenia and macrocytosis (Table 1). His peripheral blood film showed occasional hypogranular neutrophils, macrocytosis and basophilic stippling. A bone marrow aspirate revealed a hypercellular marrow with a myeloid : erythroid ratio of 0.75 : 1 . Megakaryocytes were increased in number with micromegakaryocytes and reduced ploidy. Myelopoiesis was normocellular with a shift towards the earlier forms. Promyelocytes and early myelocytes showed sparse, irregularly clumped primary granules whilst secondary granules were markedly reduced in the later myelocytes and metamyelocytes. Blast cells were 2% of all nucleated cells. Erythropoiesis was hyperplastic with megaloblastic-appearing erythroblasts and frequent multinuclear cells. Serum B12 and folate, and red-cell folate were all normal and a diagnosis of myelodysplasia (refractory anaemia) was made.

The patient was maintained on intermittent transfusions and 10 months later, in August 1985, presented with a lesion on the dorsum of his right hand. This had commenced 3 days earlier as a small blister with no obvious precipitating trauma. The general practitioner treated him with oral antibiotics but the blister increased rapidly in size. On examination he had a 4 cm diameter

Correspondence: Dr P. Yates, Department of Haematology, Southmead Hospital, Westbury-on- Trym, Bristol BSlO 5NB.

425

426 P. Yates, G. Corbett and G. Stockdill

Table 1. Haematological findings through course of patient’s illness

Hb MCV Platelets WBC and differential Date (g/dl) (fl) ( x 109/1) ( x 109/1) Film

Blast cells in

marrow

1.10.84 9.3 130 66 2.4 59% neutrophils 35% lymphocytes 6% monocytes

16.8.85 8.8 87.7 16 1.4 29% neutrophils 47% lymphocytes 20% monocytes

1 % eosinophils 3% blast cells

5.12.85 10.3 86.9 13 0.7 19% neutrophils 58% lymphocytes 19% monocytes 4% blast cells

17.1.86 7.3 87.2 16 1.3 35% neutrophils 41 % lymphocytes 15% monocytes 9% blast cells

Macrocytosis 2 % Basophilic stippling Occasional hypogranular

Basophilic stippling 5%

neutrophils

Dimorphic film Nucleated red-cells Hypogranular neutrophils Pseudo-Pelger-Huet anomaly





ecchymosis, the central area of which was necrotic and discharging serous fluid, surrounded by an area of cellulitis extending from his metacarpophalangeal joints up to his elbow. Blood cultures yielded no growth and a swab from the lesion grew Staphylococcus aureus. His blood film now showed more obvious features of myelodysplasia whilst the repeat bone marrow aspirate showed the blast cells to have increased to 5% (Table 1). He was treated with intravenous antibiotics which improved the surrounding cellulitis but the lesion itself had increased to 11 x 7 cm 48 h after admission. Despite changes in antibiotic therapy the lesion progressed to involve almost the entire forearm. He also developed similar small lesions at venepuncture sites and near a herpetic lesion on his upper lip. A central venous line was inserted to minimize further trauma to the skin. As the problem was thought to be that of a pyogenic infection in a patient with marked neutropenia and abnormally functioning neutrophils, granulocyte transfusions were commenced. These were covered with intravenous hydrocortisone and chlorpheniramine as he had reacted to blood products on previous occasions. Marked improvement in the limb followed and the other lesions healed. A week later, however, he developed extensive necrotic lesions of his right forearm which failed to respond to further granulocyte transfusions. As the appearance was of progressive gangrene, after discussion with the plastic surgeons, amputation of

Pyoderma gangrenosum and myelodysplasia 427

Figure 1. Pyoderma gangrenosum affecting the right forearm of a patient with myelodysplasia. Appearance of the arm on the tenth day after the lesion was first noticed.

the right arm above the elbow was performed. Histology of the specimen revealed a diagnosis of pyoderma gangrenosum. Retrospectively it was thought that the transient improvement in his skin condition was in fact due to the intravenous hydrocortisone rather than the granulocyte transfusions.

Two days later the patient developed further lesions on his face, trunk and left arm which were confirmed as being pyoderma gangrenosum. A consultant dermatologist recommended treatment with intravenous methyiprednisolone and later oral prednisolone. Within 2 days the lesions started to improve, eventually clearing altogether. When the dosage of steroids was reduced, further widespread skin lesions appeared. These again responded to intravenous methylprednisolone but recurred as the steroid dosage was reduced. Azathioprine was given for its steroid-sparing effect but was unsuccessful in preventing a further relapse. A trial of clofazimine was commenced but had to be abandoned because of severe arthralgia. At this stage the skin lesions which had been controlled by intravenous methylprednisolone at a daily dosage of 1 g relapsed when the daily dosage was reduced to 0.5 g. A bone marrow aspirate at this stage, in December 1985, confirmed the blast count to be 10%. An attempt was therefore made to treat the myelodysplasia with a low-dose cytosine arabinoside regimen. After a 3-week course of treatment the skin lesions had completely cleared and the steroid dosage was down to 100 mg of oral prednisolone daily. However, the patient relapsed 2 weeks later, in January 1986, with multiple widespread patches of pyoderma gangrenosum. A further bone-marrow aspirate showed 30% blast cells suggesting a transformation to acute myeloid leukaemia. He was therefore commenced on a 5-day course of daunorubicin, cytosine

428 P. Yates. G. Corbett and G. Stockdill

arabinoside and 6-thioguanine. All the skin lesions resolved but his general condition deteriorated and he died in February 1986 with pneumocystis pneumonia. At the time of his death his skin remained clear of pyoderma gangrenosum more than 3 weeks after completing the chemotherapy, and he was no longer on steroids.

Discussion

This case illustrates the importance of recognizing the association of myelodysplasia and pyoderma gangrenosum. If the diagnosis of pyoderma gangrenosum had been made earlier and treatment with high-dose steroids commenced it may have prevented the need for amputation, thus reducing the morbidity of the disease. The case also demonstrates the typical lack of response shown by patients with haematological malignancy and pyoderma gangrenosum to a variety of agents. The initial response to moderate doses of steroids was short-lived and larger doses were progressively required until eventually even I g of intravenous methylprednisolone per day failed to control the skin lesions. Therapy was therefore directed at the underlying disease initially in the form of low-dose cytosine arabinoside for the myelodysplasia and subsequently as ‘DAT 1 + 5’, a conventional chemotherapy regimen for acute myeloid leukaemia. Healing of pyoderma gangrenosum in such situations has been documented following chemotherapy (Jacobs, Palmer & Gordon-Smith 1985; Lewis, Poh- Fitzpatrick & Walther 1978). In this case there was a transient healing of the skin lesions following the low-dose cytosine arabinoside, but as the condition progressed to leukaemia the skin condition relapsed again. There was a further healing of the lesions following more intensive chemotherapy, but the patient died from complications of the leukaemia whilst still clear of further skin lesions. The most useful management for pyoderma gangrenosum in this situation may be to treat the underlying haematological disease.

Acknowledgment

We wish to acknowledge Dr G.W. Beveridge, Consultant Dermatologist, Royal Infirmary, Edinburgh, for his assistance in the management of this patient.

References

JACOBS P., PALMER S. & GORDON-SMITH E.C. (1985) Pyoderma gangrenosum in myclodysplasia and

LEWIS S.J., POH-FITZPATRICK M.B. & WALTHER R.R. (1978) Atypical pyoderma gangrenosum with acute leukaemia. Postgrad. Med. J . 61, 689-694

leukaemia. JAMA 239, 935-938

pyoderma gangrenosum and myelodysplasia

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