Diffuse painful plaques in the setting of chronic lymphocytic leukemia

Case

A woman in her seventies with a 16-year history of untreated chronic lymphocytic leukemia (CLL), diabetes mellitus, and hypertension presented with a three-month history of a painful rash and three-week history of fevers, diaphoresis, and arthralgias. The rash first appeared on the trunk with centrifugal spread to the face, extremities, palms, and soles. Physical exam was notable for reddish-brown edematous and indurated coalescing circular plaques measuring 1 to 1.5 cm found most extensively on the face (leading to mild leonine facies), upper back, buttocks, posterior thighs, and palms (Figure 1). The extremities, abdomen, and chest were involved to lesser extent. The skin was diffusely tender to palpation, with no accentuation over the lesions. There was no associated pruritus or lymphadenopathy. The patient was febrile to 38.4 degrees Celsius. A complete blood count with differential and liver function tests were within normal limits on laboratory evaluation. Blood cultures were negative after five days. Polymerase chain reaction (PCR) for ehrlichiosis and histoplasma as well as a serum cryptococcal antigen test were undetectable. A CT scan revealed a hepatic mass, splenomegaly, diffuse adenopathy, and bilateral pulmonary nodules but no parenchymal disease. Skin biopsies were obtained from the left forearm and forehead. Samples were sent to National Hansen’s Disease Program given concern for Hansen’s disease based on her husband’s history of prior employment in a leprosy hospital.

Figure 1.

Coalescing indurated, erythematous plaques on the lower back and buttocks.

What is your diagnosis?

1. Amyloidosis

2. Cutaneous Mycobacterium avium-intracellulare (MAI) infection

3. Leukemia cutis

4. Mycobacterium leprae infection

Diagnosis

• B. Cutaneous MAI infection

Microscopic Findings and Clinical Course

Histopathological evaluation revealed superficial and deep perivascular and periadnexal inflammation. The epidermis exhibited some vacuolar interface change and effacement with relatively sparse dyskeratotic cells. A lymphohistiocytic inflammatory infiltrate surrounded the blood vessels, nerves, and adnexal structures and extended into the subcutaneous fat (Figures 3–4). Acid-fast, methenamine silver, Gram, Fite, Treponema pallidum and alcian blue stains performed at our institution were all negative. Biopsies sent to the National Hansen’s Disease Program demonstrated scattered extracellular acid-fast organisms on Fite staining in the specimen of the forearm. PCR testing for M. leprae DNA was negative. DNA sequencing of the 16S ribosomal RNA gene matched MAI. In the workup of the hepatic mass, the patient was incidentally found to have large cell transformation of her CLL and for this reason was treated with bendamustine and rituximab as an outpatient. The patient received one chemotherapy infusion every four weeks for a total of 10 rounds. At her 10-week follow up appointment after two rounds of chemotherapy, all her skin lesions had resolved despite no antibiotic therapy for atypical infections.

Figure 3.

Excisional biopsy specimen (hematoxylin-eosin, original magnification x 4).

Figure 4.

Excisional biopsy specimen (hematoxylin-eosin, original magnification x 200).

Discussion

Disseminated infection with MAI is relatively rare in healthy and even immunocompromised individuals. Clinical disease is most commonly seen as an opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS) who have CD4 counts <50/mm³ or in those with pre-existing lung disease¹. Cutaneous involvement has been observed in only 14% of non-AIDS patients with disseminated MAI infection². In another study of 76 patients with MAI infection, only two involved the skin or soft tissue³. It is rare to have infection of the skin without concurrent pulmonary MAI infection, though trauma may cause isolated skin infection. The cutaneous presentation of MAI infection is highly variable and may include erythematous papules, pustules, panniculitis, infiltrated plaques, verrucous lesions, and draining sinuses³. The lesions have been reported to be painful¹.

Cutaneous findings occur in up to 25% of patients with CLL and can be due either to seeding of leukemic cells or other secondary lesions⁴. Leukemia cutis, or skin involvement by B-cell CLL, most commonly presents in the head and neck region as chronic and relapsing erythematous papules and plaques⁵. It histologically presents as monomorphic lymphocytic infiltrates accentuated around periadnexal and perivascular structures with some extending into adipose tissue². In our case, histopathology demonstrated a lack of monomorphous infiltrate and thus was inconsistent with leukemia cutis.

We hypothesize that the initially undetected worsening of CLL resulted in an immunocompromised state, which facilitated this unique presentation of cutaneous MAI infection in a non-HIV positive patient, with no clinical symptoms of active pulmonary disease. The rash was the presenting sign of both her cutaneous MAI infection and worsening CLL. Additionally, our patient’s cutaneous MAI facial involvement clinically resembled the leonine-like facies classic in lepromatous leprosy. Rare reports have been published addressing this similarity⁶.

With regards to treatment, MAI pulmonary disease is usually treated with a combination of clarithromycin or azithromycin, rifampin, and ethambutol (for nodular/bronchiectatic disease) with or without amikacin or streptomycin⁷. For limited pulmonary disease, surgical resection may be considered in patients with adequate pulmonary reserve in combination with the multidrug MAI pulmonary treatment regimen⁷. Recommended treatment duration ranges from at least three months to one year. Patients with localized MAI disease involving only the skin, soft tissue, tendons, and joints are usually treated with a combination of surgical excision and clarithromycin, rifampin, and ethambutol for six-to-twelve months⁷. In our case, we believe that chemotherapy and the subsequent reconstituted immune system likely cleared the MAI infection without targeted antibiotic treatment.

Figure 2.

Coalescing indurated, erythematous plaques on the lower extremities.