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Gorgas Case 2016-03

Epidemiology: Born in Ancash in the Andean highlands currently lives in Lima with husband. Works as an elder caregiver. Has poultry at her house. No known TB exposure. Occasional alcohol. Monogamous. Mother is 90 years old, alive and well; healthy siblings, healthy children.

Physical Examination: Alert & oriented x3. BP 80/50. HR 108. RR 22. T 36.8C. Multiple 1.5 cm indurated, non-tender on cervical, axillary and inguinal lymph nodes and one 6 x 4 cm submandibular lymph node mass. Normal heart and lung examination. Mild hepatosplenomegaly. Non-tender, non anesthetic skin lesions (see Images A,B) as shown. Neurologic examination normal.

Discussion: Positive western blot for HTLV-1. HIV negative. The large number of so-called flower cells seen in peripheral blood (Image C) are indicative of the aggressive leukemic form of ATLL which this patient had. <3% flower cells may be seen in HTLV-1 patients without ATLL. Bone marrow biopsy: 60% cellularity with presence of the 3 hematopoietic lines. Erythroid line: relative hypoplasia. Myeloid line: increased number of precursors in the center of the medullary channel; moderate increase of histiocytes showing hemophagocytosis. Lymphoid line: presence of atypical medium-sized lymphoid cells with an irregular nuclear membrane. Flow cytometry (peripheral blood sample): CD3++, CD5+/++, CD4++, CD25-/+. CD8, CD7, CD26, CD11c and CD30 negative. Pathologic proliferation of mature T-cells that represent 84.94% of the total viable cellularity. The co-expression of CD4 and CD25 corresponds to regulatory T lymphocytes and the absence of CD7 indicates a mature T-cell neoplasia with an ATLL phenotype. In an ideal situation, HTLV-1 proviral integration should be demonstrated in the atypical lymphocytes but is not necessary to confirm the diagnosis.

Skin biopsy was declined by the patient. A course of oral fluconazole has resulted in near disappearance of the skin lesions. On initial clinical presentation, this patient’s lesions over the trunk in a tropical setting provided a broad differential diagnosis. Possibilities include different varieties of tinea, even pityriasis versicolor. Annular lesions always bring to mind the possibility of leprosy; although scaliness to such a degree is not common unless the patient is having a type 1 or type 2 leprosy reaction. Non-infectious processes such as atypical pityriasis rosea or mycosis fungoides have to be included on the basis of clinical appearance alone. Pityriasis rotunda, a condition characterized by multiple round scaly patches over the trunk, with certain similarities to what is seen in this case, has been associated in South African patients with an underlying hepatocellular carcinoma.

Adult T-cell leukemia/lymphoma (ATLL) due to HTLV-1 infection is sub-divided into four categories: acute, lymphomatous, chronic, and smoldering [J Clin Oncol. 2009 Jan;27(3):453-9]. The latter two types are considered indolent and may be treated with watchful waiting until disease progression or invasion. This is somewhat analogous to the situation with chronic lymphocytic leukemia (CLL). Patients with the more aggressive forms such as this patient, generally have a poor prognosis (survival <1 year) despite aggressive conventional chemotherapy; many different regimens have provided no measurable benefit. Elevated LDH in ATLL as in this patient is also a poor prognostic indicator. Aggressive forms are associated with hypercalcemia and opportunistic infections.

A number of conditions are associated with HTLV-1 infection; [see Lancet Infect Dis. 2007 Apr;7(4):266-81 for a detailed discussion]. This patient demonstrates at least two major conditions at the same time:] adult T-cell leukemia/lymphoma (ATLL) [see Gorgas Case 2009-11] and tinea infection [see Gorgas Case 2011-7]. Extensive tinea corporis, although non-specific, has also been described as a manifestation of an otherwise undiagnosed HTLV-1 infection. Others include: strongyloides hyperinfection [see Gorgas Case 2007-04]; tropical spastic paraparesis (TSP), also called HAM (HTLV-1 associated myelopathy) [see Gorgas Case 2002-08], crusted (Norwegian) scabies [see also Gorgas Case 2008-08; infective dermatitis [see Gorgas Case 2004-07], and autoimmune disease, including uveitis, Sjögrens, arthropathy, polymyositis, tuberculosis, and thyroiditis. This patient did not have any neurological findings.

More than 90% of individuals with HTLV-1 infection remain asymptomatic for life. Worldwide, approximately 0.3-4.0% develop TSP and 1-5% develop ATLL. Although the pathogenetic mechanisms of these two major complications likely differ, the low rates of each means that it is rare to see both sequelae in the same patient. The prevalence of HTLV-1 in South America is generally underappreciated, normally being associated with Japanese and Caribbean populations. HTLV-1 is now known to occur worldwide, having originated in Africa. The highest prevalence is in Japan. In Perú, the disease is highly endemic (2-3% seropositivity) in Andean areas of the country, in Quechua populations who have had no contact with Japanese immigrants to the country. Other South American countries with significant rates of HTLV-1 include Brazil, Colombia, Argentina, and Ecuador. Transmission appears to be mainly vertical, with high associations with breastfeeding and duration of breastfeeding (probable route in our patient). The patient was breast fed at least for 2 years and provided lactation to her own children at least for 1.5 years each. Transfusion, sexual transmission, and IV drug abuse are much less important.

The most promising intervention for aggressive disease forms has been with the use of anti-viral therapy. The combination of Zidovudine (AZT) with IFN-α, if used as a first-line treatment, dramatically increases survival in acute forms of ATLL but has no effect in lymphomatous forms [J Clin Oncol. 2009 Jan;27(3):453-9]. Because of her aggressive disease the patient has been started on ZDV/3TC as IFN-α is not available to use.