Secondary Cushing's syndrome in children with juvenile idiopathic arthritis following intra-articular triamcinolone acetonide administration

J. S. Gondwe, J. E. Davidson, S. Deeley, J. Sills and A. G. Cleary

Department of Rheumatology, Royal Liverpool Children's Hospital NHS Trust, Liverpool, UK

Correspondence to: G. Cleary, Royal Liverpool Children's Hospital NHS Trust, Eaton Road, Liverpool L12 2AP, UK E-mail: gavin.cleary{at}rlc.nhs.uk

SIR, Intra-articular corticosteroid injection is a widely used treatment in the management of juvenile idiopathic arthritis (JIA) that generally induces rapid resolution of synovitis [1]. Triamcinolone hexacetonide (TH) is the preferred drug, with sustained symptom relief over longer periods than triamcinolone acetonide (TA) [2–4]. However, due to recent difficulties in obtaining TH, TA was used in our unit as an alternative agent. One hundred and ninety-five children (362 joints) and 180 children (216 joints) received intra-articular TH and TA, respectively, over a 3-yr period. Visibly prominent Cushing's syndrome developed in nine (5%) of the children who had received TA. The clinical details are summarized in Table 1.


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TABLE 1. Summary of clinical details for patients with cushingoid state after intra-articular injection

 
Intra-articular steroid injection is safe and effective in the management of JIA in children. Excessive weight gain and cushingoid appearance have been reported in adults and children following intra-articular TA injections but not with TH [5, 6]. Huppertz and Pfuller [7] reported transient suppression of endogenous cortisol release, detected by a low morning peak value of salivary cortisol, with no adverse events noted. Adrenocortical insufficiency was not formally assessed in our patient group. We did not observe a cushingoid state with TH even when multiple joints were injected, but accept that very minor weight gain or less prominent features, such as transient flushing of the cheeks, may not have been detected by this retrospective review. The development of a cushingoid state does not appear to be related to sex, age, current therapy or the type of arthritis. Although most of the children we report had multiple intra-articular injections (up to eight joints at a time with a cumulative TA dose of up to 14.5 mg/kg), Cushing's syndrome still occurred in three children who had only one or two joints injected (cases 5, 7 and 8). In our experience this side-effect was distressing for both carers and patients, although spontaneous resolution occurred, albeit over a variable period (no greater than 5 months in any patient). The resolution of hypercortisolism has been reported elsewhere to last up to 8 months [6]. We did not collect systematic data relating to the time of resolution in our patients, but none was greater than 5 months.

We undertook a separate study comparing the efficacy of 256 injections with TH and 113 with TA during the period when TH was unavailable, noting similar remission rates of 83% with TH and 87% with TA. Time to reinjection was 6.16 months with TA compared with 8.7 months for TH [8].

A cushingoid state is not uncommon after intra-articular administration of TA, including after injection of a single joint. Patients and carers should be counselled accordingly before treatment. We advocate TH as the therapy of choice because of its longer duration of action but, notwithstanding the adverse effect reported, our experience would support the use of TA as an effective alternative agent if TH is not available.

The authors have declared no conflicts of interest.

References

  1. Cleary AG, Murphy HD, Davidson JE. Intra-articular corticosteroids in juvenile idiopathic arthritis. Arch Dis Child 2003;88:192–5.[Abstract/Free Full Text]
  2. Zulian F, Martini G, Gobber D et al. Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: double-blind trial. Rheumatology 2004;43:1288–91.[Abstract/Free Full Text]
  3. Eberhard BA, Sison MC, Gottlieb BS, Ilowite NT. Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid arthritis. J Rheumatol 2004;31:2507–12.[ISI][Medline]
  4. Zulian F, Martini G, Gobber D, Agosto C, Gigante C, Zacchello F. Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis. Rheumatology 2003;42:1254–9.[Abstract/Free Full Text]
  5. Jansen TL, Van Roon EN. Four cases of secondary Cushingoid state following local triamcinolone acetonide (Kenacort) injection. Neth J Med 2002;60:151–3.[ISI][Medline]
  6. Kumar S, Singh RJ, Reed AM, Lteif AN. Cushing's syndrome after intra-articular and intradermal administration of triamcinolone acetonide in three paediatric patients. Paediatrics 2004;113:1820–4.[Abstract/Free Full Text]
  7. Huppertz HI, Pfuller H. Transient suppression of endogenous cortisol production after intraarticular steroid therapy for chronic arthritis in children. J Rheumatol 1997;24:1833–7.[ISI][Medline]
  8. Deeley S, Gondwe J, Sills JA, Davidson JE, Cleary AG. Comparison of the efficacy of intra-articular (IA) steroids in juvenile idiopathic arthritis. Arch Dis Child 2004;89(Suppl. 1):A44–A46.
Accepted 9 September 2005





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