Oculomucocutaneous syndrome

The adverse effects associated with practolol administration have been well documented (Downie 1974) and the term oculomucocutaneous syndrome was an attempt to devise an all-embracing term for the pathological features. A number of organ systems are involved in the syndrome, but individual patients may have one system more obviously damaged than others. 

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Wright P. Untoward effects associated with practolol administration oculomucocutaneous syndrome. BMJ 1975 1 595-8. 

Oculomucocutaneous syndrome occurred with chronic use of practolol (now obsolete) and even occasionally after cessation of use. ° Other members either do not cause it, or so rarely do so that they are under suspicion only and, properly prescribed, the benefits of their use far outweigh such a very low risk. The mechanism of the syndrome is uncertain. 

Rashes were part of the practolol (oculomucocutaneous) syndrome, but are infrequent with other beta-adrenoceptor antagonists. The eruptions can be urticarial, morbilliform, eczematous, vesicular, bullous, psoriasiform, or lichenoid (250-255). 

Amos HE, Lake BG, Artis J. Possible role of antibody specific for a practolol metabolite in the pathogenesis of oculomucocutaneous syndrome. Br Med f. 1978 l(6110) 402-404. 

Behan PO, Behan WM, Zacharias FJ, Nicholls JT (1976) Immunological abnormalities in patients who had the oculomucocutaneous syndrome associated with practolol therapy. Lancet 2 984... 

Adverse effects associated with practolol have been collectively described as the oculomucocutaneous syndrome. The incidence of the syndrome is small but the seriousness of the tissue damage has tended to overshadow this incidence. Practolol was marketed in 1970, and by the end of 1975 the drug had been used for some 300,000 patient years in the UK, and around one million worldwide. By October 1974, 164 cases were known, and in November 1977, the total had reached 915 (Nicholls 1978). The drug was withdrawn in 1976. It is now reasonably certain that none of the other jS-blockers in clinical use has so far induced an oculomuco-cutaneous-type syndrome. 

Table 2. Grading system for oculomucocutaneous syndrome together with cases reported at 20 November 1977...

In Wright s 27 patients, 5 had recurrent ulceration of the oral and nasal mucosa, which stopped when practolol therapy was discontinued. Although there is no argument that this is part of the oculomucocutaneous syndrome, it is not a major component. 

The main target tissues incorporated in the oculomucocutaneous syndrome are skin, conjunctiva, serosal surfaces, and peritoneum, but there are reports of fibrotic reactions affecting the lungs and liver which appear to be the result of practolol therapy. Brown et al. (1978) reported two patients who developed biliary cirrhosis after long-term practolol administration. One of the patients also had an eczematous rash and complained of dry eyes, and the second had the typical psoriasiform rash. 

VIL Oculomucocutaneous Syndrome and jS-Blocking Drugs Other than Practolol... 

Cross reactivity between the two antigens as determined in a radioimmunoassay is very low, which indicates that the benzene ring must be recognized in two halves (Gregory 1977, personal communication). These experiments demonstrate that practolol is sufficiently antigenic to induce antibody production in experimental animals but when the two derived practolol complexes were used to examine sera from patients with the oculomucocutaneous syndrome, no antibody activity could be detected (Gregory 1977, personal communication Amos 1977, unpublished work). 

The basis for considering that the oculomucocutaneous syndrome is a hypersensitivity response induced by practolol administration is a combination of clinical observations and laboratory findings which do not easily fit any alternative explanation. 

Laboratory. The earliest findings to be reported were the presence of antinuclear antibodies in the sera and IgG deposits in the basement membrane of biopsied skin (Felix et al. 1974). These findings would be compatible with a drug-induced lupus erythematosus but this is not considered part of the oculomucocutaneous syndrome. 

Drug-specific antibodies demonstrated by Amos et al. (1977) were not confined to patients with the oculomucocutaneous syndrome. Figure 9 shows an analysis of the presence of the antibody in various patient groups and it can be seen that it occurred in most patients on long-term practolol, but the titer was higher in those patients with the oculomucocutaneous syndrome (Amos et al. 1978). 

Test Group 1 Patients with the oculomucocutaneous syndrome... 

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