Bullous Pyoderma Gangrenosum as the Presenting Sign of Acute Myeloid Leukemia in a Child
A 10-year-old girl was referred to our clinic with complaints of fever persisting for >2 weeks, erythema, and tenderness on dorsum of feet for 2 days. Complete blood count was normal except for anemia (hemoglobin: 10.3 g/dL, white blood cell count: 17,000/mm3, platelet count: 221,000/mm3). An increase in acute phase reactants (sedimentation rate: 77 mm/hr and C-reactive protein: 10.1 [normal range, 0 to 0.8 g/dL]) and atypical cells on peripheral blood smear were noticed. Tests performed to search for prolonged fever and arthritis (blood antistreptolysin level, complement C3, C4 levels, antinuclear antikor, anti-ds DNA, blood angiotensin converting enzyme level), biochemical analysis of blood and postero-anterior chest radiography were normal. One day after hospitalization a bullous lesion with bloody elements inside, on right upper surface of the right foot at the metatarsophalangeal joint level was noticed (Fig. 1). Doppler ultrasonography of the lower extremities was normal. Magnetic resonance imaging of the right foot revealed cellulitis. Throat culture, aerob, anaerob, fungal culture results of the blood, liquid, and skin biopsy cultures taken from bullous lesion were all negative. Blood aspergillus antigen level (0.11 TU/mL, normal range: 0 to 0.5 TU/mL) was normal. Pathology result of skin biopsy revealed inflammatory cell infiltration within the entire dermis without malign cell infiltration. Factor V Leiden, prothrombin, MTHFR (677), and MTHFR (1298) mutation analyses were found to be normal but the patient was found to be homozygote mutant to plasminogen activator inhibitor 4G/4G. We examined peripheral blood smear and we did bone marrow aspiration and biopsy.
What is your diagnosis?
The diagnosis was acute myeloid leukemia (AML) and pyoderma gangrenosum (PG) supported by skin biopsy result and dermatology consultation. There was myeloid blasts on peripheral blood smear and bone marrow aspiration, compatible with AML-M2 examined on the third day of hospitalization.
PG is a rare idiopathic skin disease. It affects mainly adults, and only 4% of the cases are diagnosed on children and adolescents.1 There are 4 clinical forms of PG: ulcerative, pustular, bullous, and vegetative (superficial granulomatous pyoderma). An atypical form of PG exists which is more superficial and is characterized by hemorrhagic bullae that arise rapidly. This form of PG is often associated with acute leukemia and other myeloproliferative diseases. Most patients with PG have multiple lesions and the most common site of involvement is lower extremities.
Bullous or atypical PG was first described by Perry and Winklemann in 1972, characterized by rapidly evolving vesicles/bullae with central necrosis and erosion with an areola of erythema. This type of PG is considered to be due to rapid superficial necrosis. It is usually seen on the face and arms rather than on the legs. It is reported in patients who have myeloproliferative diseases like leukemia. Because of the clinical appearance, some authors believe that bullous PG and atypical Sweet’s syndrome represent different points in the same spectrum of reactive skin conditions in patients with myeloproliferative diseases.2–4
Approximately 50% of patients with PG have an associated systemic disease. These diseases may precede, follow, or occur simultaneously.5 Depending upon the associated conditions PG was also classified as follows: parainflammatory (paraimmune) (associated with inflammatory bowel disease [IBD], collagen vascular diseases, arthritis, etc.), paraneoplastic (associated with malignancy), hemotologic (leukemias, polycythemia), drug induced, and idiopathic. The most common associations are IBD, arthritis, and hematologic diseases. PG associated with IBD is characterized by ulcerative or pustular PG. PG in association with myeloproliferative diseases may present with bullous PG.2 The diagnosis is based on clinicopathologic findings consistent with the condition and the exclusion of other disorders that mimic the clinical disease.