Originalia A. Lazzarin, M. Galli, M. Introna, C. Negri, A. Mantovani, L. Mella, P. Ferrante, C. Parravicini, M. Trombini, F. Aiuti, M. Moroni, C. Zanussi Outbreak of Persistent, Unexplained, Generalized Lymphadenopathy With Immunological Abnormalities in Drug Addicts in Milan Summary: Persistent unexplained lymphadenopathy (LAS) with intermittent fever, weight loss, night sweats and malaise was observed from March to Oc- tober 1983 in 16 of 133 intravenous drug addicts who had been followed for at least two years in a Center for Drug Addicts Assistance in Milan, Italy. All the sub- jects lived in a restricted suburban area and indulged in frequent toxicomanic practices and mutual sexual in- tercourse. The subjects showed immunological altera- tions such as lymphopenia (50%), decreased T hel- per/T suppressor ratio (93%), both these abnormalit- ies (43%), decreased T helper cells (75%), increased T suppressor cytotoxic cells (81%), decreased natural killer (NK) activity (77%), anergy (50%) or hypoergy (43%) to recall skin testing and elevated levels of IgG (87%). Anti-HTLV III antibodies were found in 14 of 16 (87%) patients with LAS and in 3 of 11 (27%) symptom-free drug addicts belonging to the same group. It will be important to assess in the future whether this clinical and immunological picture results in acquired immunodeficiency syndrome in an area so far untouched by this disease. Zusammenfassung: Ausbruch yon persistierender, un- gekliirter generalisierter L ymphadenopathie mit immu- nologischen Anomalien unter Drogensiichtigen in Mai- land. Eine anhaltende ungeklfirte Lymphadenopathie (LAS) mit intermittierendem Fieber, Gewichtsverlust, nfichtlichem Schwitzen und Unwohlsein, wurde zwi- schen M~irz und Oktober 1983 bei 16 von 133 Rausch- giftstichtigen, die intraven6se Drogen benutzten, be- obachtet, die mindestens zwei Jahre lang in Mailand (Italien) in einem Betreuungszentrum fiir rauschgift- siichtige Patienten betreut worden waren. Alle diese Patienten stammen aus dem selben Vorort von Mai- land, wo sie sich h~iufig gemeinsam Rauschgift appli- zieren und augerdem wechselseitige geschlechtliche VerhNtnisse unterhalten. Folgende immunologische Ver~nderungen wurden nachgewiesen: Lymphopenie (50%), ein vermindertes T-Helfer-T-Suppressor-Zell- VerMltnis (93%), beide Anomalien zusammen (43%), eine Verminderung der T-Helferzellen (75%), eine Vermehrung der zytotoxischen T-Suppressor-Zel- len (81%), eine verminderte Aktivit~t der Natural-Kil- ler-Zellen (77%), Anergie (50%) oder Hypergie (43%) in bezug auf die Hauttestung und erh6hte IgG Serumspiegel (87%). Anti-HTLV III-Antik6rper wur- den bei 14 von 16 (87%) Patienten mit LAS und drei von 11 (27%) asymptomatischen, jedoch derselben Gruppe zugeh6rigen Rauschgiftsiachtigen nachgewie- sen. Die weitere Beobachtung dieser F~ilte in Hinblick auf ihre klinische und immunologische Entwicklung zum Vollbild des erworbenen Immundefekt-Syn- droms, in einer Gegend, die bislang von dieser Krank- heit unbertihrt war, ist entscheidend. Introduction Acquired immunodeficiency syndrome (AIDS), first re- cognized in 1981 in urban areas of the U.S.A,, particular- ly in New York and California, among homosexual men (1, 2) has been shown to affect a number of different groups at risk, even in countries other than the U.S.A. (3-9). Recently, a syndrome characterized by fever, weight loss and persistent generalized lymphadenopathy has been described in the social groups at risk for AIDS and seems to represent a prodrome for this disease (10-15). Isolated cases of overt AIDS or its prodromes have re- cently been reported in Italy (16). In this paper we are reporting on 16 intravenous drug addicts who belong to a group of subjects indulging in fre- quent toxicomanic and sexual intercourse and who deve- loped a syndrome of generalized lymphadenopathy with immune abnormalities between March and October 1983. Received: 12 June 1984/Accepted: 19 September 1984 A. Lazzarin, M.D., M. Galli, M.D. Cristina Negri, M.D., Prof. M. Mo- roni, M.D., Clinica delle Malattie Infettive, Universit~ di Milano, 1-20157 Milano; M. Introna, M.D., A. Mantovani, M.D., Istitutodi RicercheFarmaco- logiche Mario Negri, 1-20157 Milano; Laura Mella, M.D., M. Trombini, M.D., Centro per Assistenza alle Tossicodipendenze, Ospedale "L. Sacco", 1-20157Milano; P. Ferrante, M.D., Istitutodi Virologia,Universit/tdi Milano,1-20157 Milano; C. Parravicini, M.D., Cattedra di Anatomia e IstologiaPatologica V, Universit~ di Milano, 1-20157 Milano; Prof. F. Aiuti, M.D., Cattedra di Immunologia Clinica, Universitgdi Roma, I-Roma; Prof. C. Zanussi, M.D., Clinica Medica II, Universit~ di Milano, 1-20157 Milano. 372 / 14 Infection 12 (1984) Nr. 6 © MMV MedizinVerlag GmbH Mfinchen,Mtinchen1984