Case Reports 275

Herzig. G.P. (1983) High dose cytosine arabinoside therapy for refraetory leukemia. Blood. 62, 361-369.

Rassiga. A.L.. Schwartz, H.J.. Forman, W.B. & Crum. E.D. (1980) Cytarabine-induced anaphylaxis. Demonstration of antibody and successful desensitization. Archives of Internal Medicine, 140 ,42 5- 426.

Holland. J. (1984) Combination chemotherapy for refractory

lymphoma with cytosine arabinoside (A), cisplatin (P), and etoposide (E): APE. Proceedings of the American Society of Cliniral Oncology. 3, 246 (Abstract C-963).

Willemze, R., Fibbe. W.E. & Zwaan, F.E. (1 983) Experience with intermediate and high dose cytosine arabinoside in relapse and refractory acute leukemia. Netherlands Journal of Medicine, 26,

Silverman, L., Jones, R.. Norton, L., Cuttner. J., Malamud, S. & 21 5-21 9.

MULTILOBATED NUCLEI IN PERIPHERAL BLOOD LYMPHOCYTES FROM HIV + PATIENTS

Atypical lymphocytes, i.e. large, basophilic cells, are often detected in the peripheral blood of patients with HIV infection. However, to our knowledge, the presence of actual ‘mono-like’ cells with important nuclear abnormalities has not been reported. We have recently been impressed by the frequent finding of lymphocytes with bizarre nuclear shapes, particularly multilobation giving the cells a ‘clover-leaf’ appearance, in the blood of HIV+ patients. In one of these patients the nuclear abnormality was present in a significant percentage of peripheral blood lymphocytes. We report here the characteristics of this striking case.

A 38-year-old homosexual man was found in January 19 88 to be HIV + . The physical examination and the blood count were strictly normal. Two months later, an erythema- tous rash and sustained fever (39°C) appeared. Physical examination revealed enlargement of cervical, axillary and inguinal lymph nodes (1 cm diameter). The haemoglobin concentration was 11 g/dl, the WBC 6.4 x 10y/l with 1 . 5 x 109/1 lymphocytes of normal morphology, and the platelet count was 125 x 10y/l. A lymph node biopsy showed non-specific changes. The tests performed to rule out the presence of a concurrent acute infection by Epstein-Barr virus (EBV), HBV, CMV, Herpes virus and Leishmania were negative. Treponema serology tests (TPHA and FTA-abs) were positive. A diagnosis of secondary syphilis was made, he was treated with sodium penicillin and discharged.

Three months later, the patient came back to the hospital because of a new episode of sustained fever with malaise and lymph node enlargement. His physical condition had wor- sened. The examination revealed generalized lymphadeno- pathies oral candidiasis and splenomegaly (4 cm). The haemoglobin was 11.3 g/dl, the WBC 8.1 x 109/1 with 1.5 x 10y/l lymphocytes and the platelet count 70 x 10y/l. When a peripheral blood smear was examined we were struck by the presence of atypical lymphocytes (24%) with multilobated nuclei which showed a clover leaf appearance (Rieder cells) (Fig 1). The absolute number of CD4 + cells was 450x 10y/l and that of CD8+ cells was 2260x 10y/l (APAAP technique). The multilobated cells were all CD7, CD8 positive and CD4 negative. The serological tests to CMV, HBV, EBV, Herpes virus, Leishmania, Toxoplasma and Brucella were negative. Blood cultures for CMV were also negative. TPHA and FTA-abs were again positive. Antibodies against HTLV-I (ELISA, DuPont Laboratories) were not detected and serum calcium was normal. The biopsy of an enlarged lymph node was diagnostic of Kaposi’s sarcoma but

Fig 1.

no evidence of multilobated cell-type lymphoma (Pinkus’ lymphoma) was found. A diagnosis of AIDS was made.

The patient was discharged on interferon therapy and AZT. His general condition has improved, but multilobated cells are still occasionally detected in his blood smears.

The detection of clover-leaf cells in this particular case prompted us to review the blood smears of a selected group of assymptomatic HIV+ patients (13 drug addicts, 22 homo- sexuals). We have found multilobated cells similar to those described above in 10 (28.6%) out of the 35 cases. The percentage of circulating clover-leaf cells ranged between 3% and 16% of the total T cells. The immunocytochemical staining using the alkaline phosphatase anti alkaline phos- phatase (APAAP) technique showed that in five cases the

276 Case Reports

abnormal cells were CD4 + , in one case CD8 + and in four cases could be detected in both cellular subsets. Specific antibodies against CMV, HBV, EBV, HV and HTLV-I were not detected in any of these cases.

The presence of atypical lymphoid cells (multilobated nuclei) can have several causes. In the case we report here, the coincidental occurrence of an adult T-cell leukaemia/ lymphoma can be ruled out by the negativity of the HTLV-I antibodies test. The presence of nuclear multilobation in the 28.6% of HIVf patients further rules out this possibility. Regarding the remarkable case described above (360 x 10’ multilobated cells per litre), the cytological picture could be attributed to the passage to peripheral blood of multilobated- cell type lymphoma cells (Pinkus’ lymphoma) (Cerezo, 1983). However, the lymph node biopsy disclosed Kaposi’s sarcoma and absence of lymphoproliferative disease. It seems also improbable that an infection by a known virus could account for the nuclear abnormalities as it has been recently described in infectious mononucleosis (Inoue, 1989). In our case the blood picture could have been due to other rarer assymptomatic viral or bacterial infections. The only positive antibody test was that for syphilis, but this disease does not normally produce this type of cellular alteration. It has also been described that keeping the blood in EDTA containing tubes can result in this particular kind of artefact (Bessis, 1972). In our cases, however, blood smears were done

immediately after the blood sample was withdrawn, so the possibility of an artefact seems very improbable.

We would like to propose that, at least in some cases, HIV infection per se can produce these abnormalities of the nuclear shape in peripheral blood lymphocytes, although other viral diseases cannot definitely be excluded on the basis of a negative serology in the context of AIDS. Further studies are therefore necessary to rule out the presence of genomic proteins of other types of retrovirus at intracellular level in these HIV+ patients.

ACKNOWLEDGMENT

We wish to express out thanks to Dr R. Pujol-Borrell for helpful suggestions and the criticism of the manuscript.

Departments ofHaematology andhternal Medicine, J. JUNCA

Hospital Germans Trim i Pujol. B. CLOTET Badalona, Barcelona, Spain F. MILLA

REFERENCES

Bessis, M. (1972) Cellules du Sung, pp. 156-1 5 7 . Masson et cie, Paris. Cerezo, L. (1983) B-cell multilobated lymphoma. Cuncer. 52, 2277-

2280. Inoue, S. (1989) ‘Clover leaf’ nucleus of atypical lymphocytes in

infectious mononucleosis. British Journal ofHuernatologg. 70, 38 1 - 382.

HAEMOPHAGOCYTIC SYNDROME TREATED WITH CYCLOSPORIN A: A T CELL DISORDER?

Haemophagocytic syndrome is a rare syndrome character- ized by fever, pancytopenia, liver dysfunction and the proliferation of histiocytes actively ingesting blood cells, simulating the malignant histiocytosis. but distinct in that the phagocytosing histiocytes are morphologically mature (Reiner & Spivak. 1988). This syndrome occurs in patients who develop infections in the setting of pre-existing immuno- logic abnormalities or neoplasms, and usually runs a self- limited course, although in a minority of cases fatal outcomes ensue. The pathophysiologic mechanism of this condition remains unknown, but it has been suggested that T lympho- cytes secreting an excessive amount of macrophage-activat- ing lymphokines, may play a key role (Jaffe et al, 1983). Cyclosporin A is a potent immunosuppressant that has been widely used in organ transplantations. This drug selectively suppresses the function of helper T cells through the inhibition of lymphokine production and interleukin-2 recep- tor expression (Thomson & Webster, 1988). We report a case of haemophagocytic syndrome successfully treated with cyclosporin A. This case presents evidence for the concept of T cell dysfunction as a central mechanism of haemophagocytic syndrome.

A 19-year-old male student who had been in good health, developed fever, chills, and subcutaneous nodules in March 1987. Since skin biopsy showed lobular panniculitis and no underlying disorders such as pancreatic disease, a,-anti- trypsin deficiency, connective tissue disease, or haematologic malignancy were found, a diagnosis of idiopathic Weber-

Christian disease was made. On administration of predniso- lone, 60 mg daily, fever and subcutaneous nodules disap- peared, but while receiving this treatment he developed a consumption coagulopathy; the platelet count was 76 x loy/ I, prothrombin time 80 s, fibrin degradation products (FDP) more than 40 pg/ml. By increasing prednisolone to 80 mg daily, coagulopathy improved, but soon recurred on reducing the dose of steroid. Bone marrow aspirate revealed the proliferation of mature histiocytes, phagocytosing red blood cells and platelets. He was transferred to our hospital in April 1988.

The patient was markedly cushingoid, has mild hepato- splenomegaly but no lymphadenopathy. The haematocrit was 47%. white blood cells 2.3 x 10y/l with 44% band form, 23% segmented, 6% metamyelocytes, 5% myelocytes, 22% lymphocytes. Platelet count was 13 5 x 10’/dl. Prothrombin time was normal. The fibrinogen was 81 mg/l. total bilirubin 1.95 mg/dl, serum aspartate aminotransferase 97 U/l. serum alanine aminotransferase 142 U/1, and lactate dehydroge- nase 1297 U/1. The direct and indirect Coombs tests were negative. Serological studies for cytomegalovirus, Epstein- Barr virus and herpes simplex virus were negative. Computed tomographic scan of the abdomen demonstrated an abscess- like mass in the left psoas muscle, the aspirate of which was sterile purulent mucus consisting predominantly of mature histiocytes.

In May he had massive gastrointestinal bleeding which was thought to be due to steroid-induced ulcer and consump-