Erythema annulare centrifugum associated with chronic lymphocytic leukaemia

SIR, Many conditions have been described as causing or being associated with erythema annulare centrifugum (EAC). We describe a patient in whom the simultaneous diagnoses of EAC and chronic lymphocytic leukaemia (CLL) were made, an association not previously reported. A 74-year-old woman presented to the Department of Dermatology with a 3-week history of pruritic skin lesions affecting her upper back, upper arms, buttocks and thighs. On examination, there were several annular and arcuate erythematous plaques with central clearing and no scales (Fig. 1), consistent with an annular erythema. She was concurrently referred with a lymphocytosis and diagnosed as having stage A(0) CLL, which did not require active treatment. The white cell count was 16Æ2 · 10 L (normal 4Æ0–11Æ0 · 10) with a lymphocytosis of 7Æ5 · 10 L (normal 1Æ0–4Æ0 · 10). The leukaemic cells expressed an immunophenotype consistent with CLL (CD19+ ⁄CD5+, CD23+ and weak surface immunoglobulin) but unexpectedly expressed CD20 and FMC7 strongly. Interphase fluorescent in situ hybridization studies showed trisomy 12 as the sole abnormality in 24% of cells. The concurrent presentation of an annular erythema and CLL in this patient prompted suspicion that they might be linked. Cutaneous lesions in patients with leukaemia can be nonleukaemic (or ‘nonspecific’) such as caused by infections, drug reactions, vasculitis or secondary to a haemorrhagic

surface immunoglobulin) but unexpectedly expressed CD20 and FMC7 strongly. Interphase fluorescent in situ hybridization studies showed trisomy 12 as the sole abnormality in 24% of cells.
The concurrent presentation of an annular erythema and CLL in this patient prompted suspicion that they might be linked. Cutaneous lesions in patients with leukaemia can be nonleukaemic (or 'nonspecific') such as caused by infections, drug reactions, vasculitis or secondary to a haemorrhagic  diathesis. 2 More rarely, neoplastic lymphocytes are found within the skin and these lesions are known as leukaemia cutis (or 'specific' lesions). In the context of CLL, both cutaneous findings in general 3 and specific leukaemic cutaneous infiltrates 4 have been reviewed.
An initial skin biopsy in our case showed a moderately intense superficial perivascular infiltrate composed predominantly of lymphocytes with several eosinophils. The epidermis showed focal spongiosis containing occasional eosinophils. A second biopsy showed similar changes but with minimal spongiosis, a more closely clustered arrangement of the infiltrate around superficial blood vessels and very few eosinophils (Fig. 2). No fungi were seen in periodic acid-Schiff-stained sections. Direct immunofluorescence on perilesional skin, taken to screen for early bullous pemphigoid, was negative. Immunocytochemistry demonstrated that the infiltrate was predominantly CD3 and CD5 positive, confirming a predominance of T cells, and CD23 negative, thus excluding leukaemia cutis. Interestingly, the first biopsy coincided with a peripheral blood eosinophilia of 2AE27 · 10 9 L )1 (normal 0AE04-0AE4 · 10 9 ), but this was resolving by the time of her second biopsy, and prior to treatment.
Having ruled out more specific categories of annular erythema (erythema chronicum migrans, erythema gyratum repens, erythema marginatum), and those associated with anti-SSA (anti-Ro) and anti-SSB (anti-La) antibodies, 5 a diagnosis of EAC was made. The pathological findings favour what has been controversially termed 'superficial' EAC in which the dermal infiltrate is superficial, spongiosis is found in 80% of cases and eosinophils are observed in around one third of cases. 6 Our patient's skin lesions did not respond to potent topical steroids but to a reducing course of oral prednisolone starting at 30 mg daily.
EAC has been associated with drugs and a wide variety of disorders including infections, endocrine and immunological disorders, haematological and other neoplastic disorders. 1 Annular erythemas have been described as the clinical presentation of bullous pemphigoid 7 and hypereosinophilic dermatitis 8 in two patients with CLL but, to the best of our knowledge, EAC per se has not been described in association with CLL. Although this association may be coincidental, the close temporal association prompts us to speculate that EAC in this case was a nonspecific manifestation of CLL.  (Fig. 1). The patient complained of mild pruritus and asthenia without weight loss. Physical examination was otherwise unremarkable, without palpable nodes or spleen. Blood analysis revealed lymphocytosis at 8AE54 · 10 9 L )1 (normal 1AE5-4AE0 · 10 9 ), with a normal erythrocyte and platelet count. Blood and bone marrow immunophenotyping showed that most of the lymphocytes were CD20, CD19, CD5 and CD23 positive, leading to the diagnosis of chronic lymphocytic leukaemia (CLL). Polymerase chain reaction (PCR) analysis showed a main B-cell clone in the blood. Fluorescent in situ hybridization study of blood lymphocytes showed a chromosome 13 deletion. Chest, abdominal and pelvic X-ray was normal and the CLL was classified as Binet stage A.
Skin biopsy revealed a deep dermal perivascular infiltrate of small nonatypical lymphocytes, without vasculitis, and only a few interstitial lymphocytes (Fig. 2a). The epidermis was normal. The underlying subcutaneous fat was not involved. The infiltrate was composed of T lymphocytes, stained by anti-CD3 antibody (Fig. 2b), and a minority of B lymphocytes as revealed by anti-CD20 staining (Fig. 2c). Only a few B lymphocytes expressed CD23 antigen (Fig. 2d), which is characteristic of CLL lymphocytes. CD5 was difficult to analyse because of the staining of T lymphocytes. PCR study of the skin biopsy showed a polyclonal profile within a very weak B-cell clone