AIM: We studied the pathogenesis of puffy hand syndrome of intravenous drug use. 
We hypothesized that injections of high-dose sublingual buprenorphine, instead 
of the recommended sublingual administration, could play an important role in 
lymphatic obstruction and destruction.
DESIGN AND PARTICIPANTS: We set up a case-control study in substitution centres, 
recruiting intravenous drug addicts with and without puffy hands, respectively. 
The subjects were asked to answer anonymously a questionnaire of 40 items 
comprising social and demographic status, history of illicit drugs use, 
buprenorphine misuse and injection practices.
FINDINGS: We included 33 cases and 33 controls, mean age of 34 years. They were 
past heroin users, mainly methadone-substituted. In multivariate analysis, sex 
(women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03), 
injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR = 
7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% 
of the cases and 59.4% of the controls, respectively, there was a high-dose 
sublingual buprenorphine misuse, although it appeared not to be a significant 
risk factor for puffy hand syndrome.
CONCLUSIONS: Injection practices are likely to cause puffy hands syndrome, but 
buprenorphine misuse should not be considered as a significant risk factor. 
However, intravenous drug users must still be warned of local and systemic 
complications of intravenous drug misuse.