Regression of uraemic pruritus by cyclosporin treatment in a haemodialysis patient

Sir,

Recent studies suggest that low dose (2.5–3.0 mg/kg daily) cyclosporin treatment is an effective, safe and well-tolerated treatment for atopic dermatitis which is refractory to conventional treatment modalities. This treatment can also lead to long-term remission of the disease in some patients [1].

Uraemic pruritus is a distressing disease that is difficult to treat. Its prevalence is high in the dialysis population. An effective treatment of severe uraemic pruritus is needed, as its consequences can be devastating for the patients. We describe the case of a 78-year-old woman who, at the end of 1999, 2 years after the beginning of haemodialysis, developed intense and generalized pruritus. Secondary hyperparathyroidism, dry skin, hyperphosphataemia, anaemia, peripheral neuropathy, high aluminium levels and hypervitaminosis A were all excluded. Although Kt/V was already satisfactory at 1.5, duration of dialysis was increased to 240 min, a more biocompatible membrane (polymethylmethacrylate) was used and swine heparin was changed with an EDTA-purified preparation. Other causes of pruritus (metabolic and endocrine diseases, biliary obstruction, myeloproliferative diseases, polycytaemia vera, iron deficient anaemia and cancer) were excluded.

Symptomatic treatment with antihistamines, steroids and ultraviolet B (UVB) light were ineffective. Rather, the intensity of pruritus worsened, determining a deterioration of the quality of life to the point of an attempted suicide. Therefore, in November 2000, immunosuppressive treatment with cyclosporin was attempted. Starting doses of 200 mg/day were tapered to reach and maintain a therapeutic range between 130 and 160 ng/ml. Serum levels of the drug were monitored weekly at the beginning of treatment and every other week in the maintenance phase. By December 2000, symptoms improved and eventually regressed. In March 2001, cyclosporin was reduced and stopped, but severe pruritus quickly recurred. The patient again expressed suicidal thoughts. Therefore, at the beginning of 2002, a new course of cyclosporin treatment was started. Again, symptoms markedly improved, but in April 2002 treatment was stopped because of cholestatic jaundice due to two biliary stones in the choledocus. Interestingly, jaundice developed in the absence of pruritus, which recurred immediately after the interruption of cyclosporin treatment. Endoscopic papillectomy resolved this complication and in June 2002 treatment with cyclosporin (associated with ursodesossicolic acid, 300 mg/day) was resumed. Since then, our patient has remained in good clinical and psychological conditions. Cyclosporin demonstrated a good safety profile during long-term treatment and was, generally, tolerated well.

Several different therapies have been proposed for uraemic pruritus: antihistamines, opiate antagonists and even placebo have been reported to be effective in previous reports, but many patients, including ours, do not respond to any treatment. Recently, Mettang et al. [2] pointed out that research on the pathogenesis of uraemic pruritus is concentrating in two areas: the ‘opioid hypothesis’ and the ‘immuno-hypothesis’. The former is controversial and is based on the finding that several µ-receptor-agonistic drugs can induce pruritus and is supported by the observation that administration of opiate antagonists was successful in the treatment of cholestatic pruritus. Indeed, in a preliminary study of uraemic patients, Peer et al. [3] demonstrated that naltrexone, an oral µ-receptor antagonist, was effective in relieving symptoms in all of the treated patients. However, Pauli-Magnus et al. [4] could not reproduce these results in a larger cohort treated for a longer time (4 weeks).

The immuno-hypothesis is the base of the therapeutic approach we chose for our patient. According to this hypothesis, uraemic pruritus is a systemic disease due to a derangement of the immune system with a pro-inflammatory pattern [2]. In support of this hypothesis, uraemic pruritus is extremely rare in transplanted patients with renal failure, as long as cyclosporin treatment is maintained [2]. The IL-2-suppressing effect of cyclosporin might correct the immunological disturbances causing some of the most severe forms of uraemic pruritus. Our case confirms the efficacy of this approach in a haemodialysis patient with very severe clinical manifestations of the disease, which led her to attempt suicide. In this unblinded single patient we cannot exclude a placebo effect, which can be particularly relevant in patients with pruritus. However, no placebo effect could be observed with all the other treatments (antihistamines, steroids and UVB light) carried out in this patient. In addition, a consistent pharmacological effect from cyclosporin is indicated by the response to challenge, withdrawal and rechallenge.

Although the potential side effects of an immunosuppressive drug in dialysis patients should be kept in mind, our results indicate that cyclosporin treatment might be a new effective approach to severe uraemic pruritus refractory to conventional treatment modalities, provided that appropriate patients are selected and careful monitoring is performed. Our observation and hypothesis need to be confirmed by a placebo-controlled double-blind trial.

Conflict of interest statement. None declared.

Maria Fusaro1, Giorgio Munaretto1, Michela Spinello1 and Maurizio Gallieni2

Nephrology and Dialysis Unit 1Hospital of Chioggia, Venice 2San Paolo Hospital, Milan Italy Email: gallieni{at}iol.it

References

  1. Berth-Jones J, Graham-Brown RA, Marks R et al. Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis. Br J Dermatol 1997; 136: 76–81[CrossRef][ISI][Medline]
  2. Mettang T, Pauli-Magnus C, Alscher DM. Uraemic pruritus: new perspectives and insights from recent trials. Nephrol Dial Transplant 2002; 17: 1558–1563[Free Full Text]
  3. Peer G, Kivity S, Agami O et al. Randomised crossover trial of naltrexone in uremic pruritus. Lancet 1996; 348: 1552–1554[CrossRef][ISI][Medline]
  4. Pauli-Magnus C, Mikus G, Alscher DM et al. Naltrexone does not relieve uremic pruritus: results of a randomized, placebo-controlled crossover-study. J Am Soc Nephrol 2000; 11: 514–519[Abstract/Free Full Text]