Recurrent pyoderma
gangrenosum and myelodysplasia
Au WY,* Ng WM,° Yeung CK,* Chan HH,* Jones BM^
Departments of Medicine,* Surgery° and Pathology^, Queen Mary
Hospital, University of Hong Kong
Correspondence: Dr Au; University Department of Medicine;
Professorial Block; Queen Mary Hospital; Pokfulam Road. Hong Kong.
Tel: (852) 2 855 4792. Fax: (852) 2 974 1165. Email:
auwing@hotmail.com
Pyoderma gangrenosum (PG) is a neutrophilic dermatoses diagnosed
clinically and histologically, with intense dermal neutrophilia
and inflammation, in the absence of vasculitis.1
Approximately half of all cases are associated with systemic
disorders, including inflammatory bowel disease (IBD: ulcerative
colitis and Crohn's disease), rheumatoid arthritis,
myeloproliferative diseases, myeloma and non-Hodgkin's
lymphoma.2
A 66-year-old woman presented
with an 8-cm extensive cutaneous abscess with necrosis in the
right thigh. There was no history of trauma or diabetes. A
complete blood count showed a hemoglobin level of 8g/dl, white
cell count of 12x109/L, with 5% circulating blast cells
and a platelet count of 356x109/L. A bone marrow biopsy
showed myelodysplasia (MDS) with a 13% blast and t(1;18)
cytogenetic abnormality. The abscess was drained, resulting in a
discharging sinus for three weeks, and her MDS was managed
conservatively. Over the next three months, however, she developed
painful gangrenous pustular patches over the shoulder, calf and
trunk requiring excision and skin grafting (Figure
1)., with histological
features of PG. A neutrophil function test showed isolated
impaired chemotaxis (Table
1), characteristic of
PG.3 On mixing study, a primary defect in the patient
neutrophil was noted, with no plasma inhibitor of chemotaxis. In
view of age, induction chemotherapy, high dose steroids or bone
marrow transplantation (BMT) was not planned. At one-year
follow-up, the patient is kept on regular transfusion and
intermittent short courses of prophylactic antibiotics.
Pyoderma gangrenosum is commonly seen in patients with IBD, but is
also seen in the context of hematological malignancies. Very few
series of non-IBD cases have been reported,4-6 but
hemic malignancy is the leading cause of para-neoplastic
PG.7 The underlying defect in PG is invariably a
chemotaxis defect, leading to inefficient dermal crowding of
neutrophils.3,8 For IBD and myeloma, a serum chemotaxis
inhibitor can be demonstrated. Patients improve with
plasmapheresis and treatment of the primary
condition.2,9 Steroids may be used to reduce the
inflammation and the production of chemotaxis inhibitors, but up
to one year may be needed for complete clinical
response.5 Myelodysplastic syndrome is marrow stem cell
disorder that affects the maturation and function of all three
lineages of blood cells. Defects in platelet function manifest as
bleeding diathesis despite normal platelet counts, and abnormal
platelet function tests are often used to support morphological
features for the diagnosis of MDS. Acquired functional deficits of
white cells are often overlooked. Like platelet function tests,
"neutrophil function tests" may be clinically relevant and
diagnostically useful. Clinically, extensive PG may occur in MDS
patients, even in extra-cutaneous sites,10 and some
studies showed that PG account for 10% of all leukemia associated
neutrophilic dermatosis.11 Hence, in patients with
unexplained PG, careful examination of neutrophil morphology and
function, with or without marrow and cytogenetic assessment, will
be needed. Conversely, primary PG may be diagnosed in MDS patients
after exclusion of other causes of skin ulcers such as drugs
(hydroxyurea), vasculitis and cryoglobulins. Like the rare
congential neutrophil function disorders (e.g. chronic
granulomatous disease), BMT will be needed for full correction of
MDS neutrophil function and eradication of PG relapse.
Interestingly, despite its immunosuppressive effect, steroid is
also reported to be useful in patients with leukemia related
PG.6 There is evidence to suggest that steroids may
actually help chemotaxis by impeding random neutrophil
movements.12 However, in our case, remission of PG was
achieved by suitable antibiotic and surgical care. The relative
risk and benefit of high dose steroids in leukemia related-cases
will need individual assessment.
