High dose inhaled Corticosteroids can cause Achilles Tendonitis
Article Outline
- Summary
- Case report
- Discussion
- Conflict of interest statement
- Appendix. Supplementary data
- References
- Copyright
Summary
Management of Chronic Obstructive Pulmonary Disease (COPD) patients involves use of inhaled steroids, which are known to reduce exacerbations and improve respiratory symptoms. Nevertheless evidence suggests that oral steroids can cause tendonitis, in particular Achilles tendonitis and rupture. Here we present a case report of a patient who had moderate COPD confirmed by spirometry and was started on inhaled steroids. Following this, the patient developed Achilles tendonitis which was confirmed by ultrasonography and further by reproduction of symptoms and signs by dechallenge/rechallenge strategy. To our Knowledge, this is the first report that demonstrates the association of inhaled steroids with tendonitis in COPD patients. While inhaled steroids might be useful in management of COPD patients; development of tendonitis as a consequence of this treatment deserves careful thought.
Keywords: COPD, Inhaled Corticosteroids, Achilles tendonitis
Inhaled Corticosteroids are widely prescribed and have an important role in the management of Chronic obstructive pulmonary disease (COPD),1 Inhaled steroids have been shown to decrease the number of exacerbations and reduce respiratory symptoms in a subgroup of COPD patients. High dose inhaled corticosteroids have a favorable risk/benefit ratio in patients with advanced disease, particularly those with frequent exacerbations, however no proven benefit has been reported in patients with milder disease.2
Atraumatic Achilles Tendonitis (defined as painful inflammatory and/or degenerative changes in the Achilles tendon) is associated with the intake of systemic corticosteroids, as well as with fluoroquinolone antibiotics. In a number of reported cases of achilles tendonitis, oral steroids were being used for patients with asthma or COPD. However there is much less evidence of Achilles tendonitis being associated in patients using inhaled corticosteroids. Here we present a case of a patient with COPD who developed Achilles tendonitis on receiving a high dose inhaled corticosteroids; we present evidence that inhaled steroids were the cause of this tendonitis.3
Case report
Case: A 69 year old man, a welder by profession, was referred to the respiratory clinic for assessment of his COPD. His past medical history included Abdominal Aorta Repair, Coronary artery by-pass operation for Ischemic Heart Disease, Osteoarthritis of both knees and Dyslipidemia. His medication included Bisoprolol, salbutamol via a metred dose inhaler as required, Perindopril, Aspirin, Simvastatin and Omeprazole.
On assessment in the clinic he had dyspnoea for 10 years, with a decreased exercise tolerance and he had a number of exacerbations in the last year. He was an ex-smoker with a smoking history of 80 pack years. Spirometry performed in clinic revealed a forced expiratory volume (FEV1) of 0.97
l increasing to 1.1l after 400mcg of Salbutamol. On Spirometry he had moderate COPD (as per NICE Guidelines) with FEV1 of 42% of predicted and an obstructive pattern with a FEV1/FVC ratio of 52%.
He was started on a maximal inhaled treatment of Salbutamol (2 puffs 4 times a day), Tiotropium −18mcg once a day, Seretide 500 Accuhaler twice a day (a combination of fluticasone 500mcg and Salmeterol 50mcg). At follow up, he complained that he had had severe pain in both of his heels over the area of Achilles Tendons that started two weeks after starting the Seretide. Therefore he stopped the statin and the inhaled steroid (Seretide) and the symptoms resolved completely. On reintroduction of inhaled steroid the symptoms of tendonitis recurred again after two weeks. On examination there was some swelling and crepitus felt over the Achilles Tendons, after which, he was advised to stop Seretide for the second time, this again resulted in complete resolution of his symptoms.
Evidence of focal thickening and increased vascularity in the area of Achilles Tendons was observed on performing an ultrasound of his tendons; radiologically confirming the clinical diagnosis of Achilles tendonitis.
Discussion
This patient was appropriately started on high dose inhaled Corticosteroids combined with a long acting beta agonist, as his FEV1 was less than 50% predicted and he had a number of exacerbations in the prior year, this was in line with the national guidelines.1 In spite of a good safety profile of Seretide, he developed bilateral Achilles tendonitis, as a side effect of the drug.
Evidence in literature suggests that patients receiving high dose of oral steroids can develop Atraumatic Achilles Tendonitis. Hence, Atraumatic rupture is most prevalent in patients with rheumatoid arthritis, lupus erythematous, gout, hyperparathyroidism and chronic renal failure. In several cases of intermittent use of oral steroids for asthma and COPD, patients developed achillies tendonitis and in some cases rupture of the tendon. Histological studies done using biopsies from Achilles tendon revealed altered fibres structure and arrangement, focal variations in cellularity, extracellular glycosaminoglycans, neovascularization, and hyalinization. However there was no evidence of inflammatory cell infiltration.4 Doppler studies have confirmed the presence of increased vascularity in symptomatic tendons.5
Evaluation of literature showed that dosage or duration of steroid use had no correlation with the extent of injury. Cases of local steroid injections causing Achilles tendonitis have also been reported. The occurrence of tendonitis with inhaled corticosteroids must however be rare, as to our knowledge this is the first report in the literature of Tendonitis occurring in a COPD patient on inhaled Corticosteroids without any concomitant systemic steroids.
The clinical diagnosis of tendonitis in this patient was based on symptoms including pain in calf and over the heel. Furthermore, dorsiflexion of the ankle increased pain and tenderness and a tendon friction rub and swelling over the tendon was palpable. The clinical diagnosis was subsequently confirmed by the radiological findings.
According to the Yale algorithm for the assessment of drug-event association, this patient scored 5 points on the algorithm.6 Using this algorithm a total score is obtained, and the score can be used to assign a category to adverse effects caused by a certain drug. In this case, a score of 5 suggested that causation was highly probable, but not definite. We believe that the strongest evidence for our hypothesis that high dose inhaled corticosteroids caused Achilles tendonitis in this man was obtained by ultrasound examination of the ankle and the results of the dechallenge/rechallenge strategy.
Seretide is a combination of an inhaled Corticosteroid and a long acting beta agonist. It could therefore be possible that the Tendonitis was due to the long acting beta agonist or due to an interaction between the long acting beta agonist and the inhaled Corticosteroid. However it is more likely that the inhaled Corticosteroid was causative agent, as many different Corticosteroids have already been associated with Tendonitis. It should be noted that unlike patients in other reports, this patient was not taking any systemic corticosteroids or fluoroquinalone antibiotics. Nor had he taken any of these medications in the 3 months prior to developing bilateral Tendonitis.
These observations above confirm that inhaled Corticosteroids can cause tendonitis in patients with COPD. As Seretide is commonly prescribed in asthma and COPD, the development of this side effect must be a very rare event, as it is not seen in the literature. We think this association deserves consideration, because of the possible devastating affects of Tendonitis progressing to Tendon rupture, in these already debilited patients. While inhaled steroids are useful in the management of COPD patients; the development of tendonitis as a consequence of this treatment deserves to be brought to clinicians attention.
Conflict of interest statement
The authors have no conflict of interest.
Appendix. Supplementary data
References
- . Clinical Guideline 12. Chronic obstructive pulmonary disease. Management of chronic obstructive pulmonary disease in adults in primary and secondary care; 2004;
- . Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000;320:1297–1303
- . Corticosteroid-associated tendinopathies: an analysis of the published literature and spontaneous pharmacovigilance data. Drug Saf. 2005;28(7):633–643
- . Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients. Acta Orthop Scand. 1997;68:170
- Achilles tendon and paratendon microcirculation in midportion and insertional tendinopathy in athletes. Am J Sports Med. 2006;34:92
- . The Yale algorithm. Special workshop – clinical. Drug Inf J. 1984;18:283–291
PII: S1755-0017(08)00091-2
doi:10.1016/j.rmedc.2008.10.006
© 2008 Elsevier Ltd. All rights reserved.
