To the Editor: The interesting case report by Currie and colleagues describes a variable cutaneous eruption of uncertain aetiology in a cluster of methadone-dependent patients.1 The rash was described as including pruritic, exanthematous, purpuric and eventually desquamative components, and typically as involving the trunk and extremities, particularly palms and soles.

Secondary syphilis classically presents in a similar fashion, but no mention was made as to whether this had been excluded by serological testing. Indeed, the histology of the rash (perivascular inflammation, including plasma cell infiltrate, progressing to endarteritis) is similar to that seen in skin biopsies from methadone patients with secondary syphilis. However, an allergic or toxic cause appears to be implicated, in view of previous, well documented reports of hallucinogenic or other drug-related vasculitis published by ourselves2 and others.3-5

To the Editor: As a Victorian always on the lookout for something new, I read with interest the report by Currie and colleagues of a syndromic rash in patients attending methadone clinics in New South Wales.1 From the title I expected to read about a rash occurring as part of a syndrome, yet no group of concurrent symptoms was described. In fact, there was a long list with each patient of negative findings. I also had trouble deciding whether the four patients described indeed had the same rash. While the “lumpers” among us may consider it pedantic to split “rash” into more than one category, some doctors make an occupation of it quite successfully.

For example, Patient 1 had petechiae and purpura, but no erythema and no involvement of the palms and soles. No photo, but nevertheless a nice description of vasculitis — common among intravenous drug users. Patient 2 had, from the look of the photo, a toxic erythema that resolved with desquamation of the palms and soles. No petechiae or purpura. Therefore, must be a different rash to Patient 1. Patient 3 is described as having “ a prominent purpuric rash involving both lower limbs”. However, the photo shows a macular erythema with some associated purpura that looks almost certainly to be an incidental manifestation of dependency. Difficult to say from a photo, as touch is so important in the diagnosis of true purpura. Of course, a 2 mm punch biopsy of the skin could resolve this almost instantly. Again, it is not clear whether this rash is similar to that seen in either Patient 1 or Patient 2.

Patient 4 is described as having a red and itchy rash (erythematous and pruritic), but, from the photograph, we can clearly see that the rash is urticarial. This raises the possibility of urticaria, or urticarial vasculitis, or even erythema multiforme. Again, a skin biopsy would be very useful. The severe palmar peeling almost seems incongruous, but it does give me faith that buried in this report there might actually be a new desquamating rash associated with methadone use.

In summary, I am still not clear whether the four patients described had the same rash, but I concur with the authors that several of these patients might warrant specialist assessment. Let’s hope they get it.

In reply: The purpose of our report1 was to alert the wider medical community to the recent outbreak of a “syndrome” (“a group of symptoms and signs, which, when considered together, are known or presumed to characterise a disease or lesion”2) that included the development of various forms of rash in patients taking methadone syrup. Our report included four cases illustrating the different types of rash encountered to date.

From October 2004, over 400 cases were reported from methadone clinics in New South Wales, although very few new cases have been reported since February 2005, presumably reflecting the success of preventive measures instituted by the NSW Health department. To date, the cause of this methadone-associated syndrome has not been elucidated.

Skin biopsies of rash lesions have been performed in a number of our patients. All have shown chronic perivascular inflammation, with most demonstrating hyperkeratosis. A small number of patients have had a true leukocytoclastic vasculitis. As Heazlewood has commented, both secondary syphilis and illicit drugs such as amphetamines and cocaine have been reported to cause vasculitic rashes. However, none of the more than 50 patients in whom we have performed syphilis serological testing has had positive results, and few of our affected methadone patients have had urine drug-test results positive for amphetamine or cocaine use. We therefore believe that the syndrome we have described remains specific to the patients’ current use of methadone syrup.

We are unaware of a rash that is “an incidental manifestation of dependency”, as suggested by Sinclair, but we would assure him that specialists from a wide variety of fields, including dermatology, immunology, immunopathology, infectious diseases, addiction medicine and epidemiology, have all been involved in the assessment and treatment of patients with this syndrome, and in the wider investigation of its pathogenesis.