Bullous pyoderma gangrenosum as a manifestation of leukemia cutis

ARTICLE

Pyoderma gangrenosum is associated with underlying systemic disorder in 60-80% of cases [1]. This includes inflammatory bowel diseases, seronegative and seropositive arthritis, paraproteinemia, myeloma, polycythemia rubra vera, myelofibrosis and leukemia [2-4]. In 1972 Perry and Winkelmann first described the association of an atypical, superficial bullous variant of pyoderma gangrenosum in three patients who had rapidly progressive myeloid leukemia [5]. Up to now concomitant occurrence of gangrenous pyoderma and leukemia has been described in more than 40 cases, most of which exhibited a superficial bullous form of the disease [6]. We present a patient who developed acute myeloid leukemia soon after the initial appearance of bullous pyoderma gangrenosum.

Case report

Case history: a 67 year old female patient. 3 weeks before admission the patient complained of chills, fever and joint pain. Nodes developed on the lower limbs, but later most of them disappeared. Due to earlier complaints of weakness and loss of weight the patient was first seen at another hospital, though examinations failed to reveal any disease.

Clinical status: poor general condition; a concentric, hemorrhagic, vesico-bullous erosion with collapsed sides and a pale erythematous areola on the right knee of about 15 cm in diameter (Fig. 1). A hemorrhagic, brownish-black crustous plaque and papule on the right eyebrow and left side of the nose. Several pustules all over the trunk. Within a week the knee lesion showed a slow peripheral expansion. Enlarged liver (about 3 cm beyond the costal arch). The spleen and the lymphatic nodes were not palpable.

Laboratory data and findings: sedimentation rate (Wgr): 134 mm/h; mild anemia (Hgb: 5.8 mmol/L; htk: 0.31); platelets: 210 thousand; WBC: 7,200; differential white blood count: shifted to the left with several atypical (blast?) cells. Liver and renal function tests normal; urinalysis and serum uric acid normal; glucose tolerance decreased. The patient rejected a bone marrow biopsy. Several days later a marked increase in WBC count: from 39 thousand to 51 thousand a week later. A malignant hematological disease was suspected. Diagnosis of acute myeloid leukemia was verified by a Jamshidi-biopsy.

Histology: intraepidermal vesicle formation in the epithelium. Massive neutrophil and to a lesser extent eosinophil granulocyte infiltration and microabscesses in the dermis, also involving adipose tissue. Marked RBC extravasation; minor leukocytoclasia. Decaying cells occurred among atypical giant cells with large nuclei. Fibrinoid degeneration of the vessel wall with inflammatory cell infiltration was also observed. Special staining techniques (naphthol ASD, chloroacetate-esterase, CD15 and CD68) revealed that most of the infiltrating cells were of leukemic origin (Fig. 2).

Course of the disease and therapy: the patient was admitted to the Department of Hematology of the 2nd Dept. of Internal Medicine, Szeged University of Medicine (SZOTE). Remission was induced by a combined induction-, two consolidation- and supportive therapy. Later, ulceration of the right knee lesion occurred, which healed only after a treatment lasting several months.

Discussion

Pyoderma gangrenosum and Sweet's syndrome are two remote points of the same nosologic spectrum (neutrophilic dermatosis) [7]. Within this spectrum bullous pyoderma gangrenosum and vesiculous Sweet's syndrome are closely related and therefore these two atypical forms can scarcely be differentiated. In certain cases differentiation is impossible [3, 8]. There is evidence that the same patient had both atypical forms [7, 9]. Certain cases with a similar clinical and histological picture published in the literature were interpreted by different authors either as a vesiculous Sweet's syndrome or as a vesiculo-bullous pyoderma gangrenosum [6, 10]. Such transient forms occurring in leukemia, in which these two atypical neutrophilic dermatoses could not be differentiated and where the symptoms show transition during the course of the disease, were cleverly termed by Cooper as a leukemic neutrophilic dermatosis [11].

At the onset the symptoms rather resemble vesiculo-bullous Sweet's syndrome, where the diagnosis is verified by the presence of two major and at least two minor symptoms of Sweet's syndrome [12]. However, the development of central necrosis which is later transformed into a persisting, superficial ulceration with livid edges healing with a scar, is characteristic of pyoderma gangrenosum. In contrast to the above findings, ulcers which develop in pyoderma gangrenosum are deeper, with abundant purulent secretion and dug-in edges. Formation of vesicles, pustules, and hemorrhagic loci, as well as the general symptoms and a dense neutrophilic infiltration and formation of microabscesses in histology, are mutual features of both atypical forms. It is noteworthy that in our case both mature neutrophil leukocytes and leukemic cells could be found in the dermal infiltrate.

The pathogenesis and the link between pyoderma gangrenosum and leukemia are poorly understood. Leukocyte colony-stimulating or other bone marrow factors, as well as chemotherapy might play a role in the development of the symptoms. There is evidence that GMCSF is involved not only in the development of Sweet's syndrome, but also of pyoderma gangrenosum [13, 14].

In our patient the atypical vesiculo-bullous pyoderma gangrenosum was the first symptom of acute myeloid leukemia, which helped us to correctly diagnose the main disease. Pyoderma gangrenosum has been previously assumed as an unambiguous paraneoplastic disease, because the infiltrated cells could not be studied with immunecytological markers. In our case we could verify that some cells in the infiltrate were of leukemic origin. There is a recent evidence that in cases of leukemia accompanied by Sweet's syndrome and gangrenous pyoderma, some of the cells can get into the skin from the leukemic bone marrow and migrate back from the skin into the marrow [15, 16]. Specific skin infiltrates in myelogenous leukemia probably occur as a result of tissue-selective homing of a unique subpopulation of malignant myeloid clones. Considering the above finding, our case of atypical bullous pyoderma gangrenosum covers the term of leukemia cutis (skin infiltration by leukemic cells) as well. An atypical, bullous clinical picture of a pronounced dermatosis, especially if combined with anemia, thrombocytopenia (hemorrhagic foci), and the appearance of immature cells in the smear, usually indicates a myeloproliferative disease with a severe course.

Article accepted on 11/4/00

CONCLUSION

REFERENCES

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