Top

Osteoporosis International

Published in:

01-05-2010 | Review

Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity

Authors: P. Musette, M. L. Brandi, P. Cacoub, J. M. Kaufman, R. Rizzoli, J.-Y. Reginster

Published in: Osteoporosis International | Issue 5/2010

Abstract

Summary

Cutaneous adverse reactions are reported for many treatments including antiosteoporotic agents. This position paper includes an algorithm for their recognition. With early recognition and proper management, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration, and systemic corticosteroids, if necessary, the prognosis is good.

Introduction

Cutaneous adverse reactions are reported for many therapeutic agents and observed in between 0% and 8% of treated patients depending on the drug. The antiosteoporotic agents are reputed to be safe in terms of cutaneous effects; however, there have been a number of case reports of cutaneous adverse reactions, which merit consideration. This was the subject of a Working Group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, to focus on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. We prepared this position paper following these discussions, and include an algorithm for their recognition.

Methods

We reviewed cutaneous adverse reactions observed with antiosteoporotic agents, including information from case reports, regulatory documents, and pharmacovigilance.

Results

The cutaneous adverse reactions range from benign reactions including exanthematous or maculopapular eruption (drug rash), photosensitivity, and urticaria to the severe and potentially life-threatening reactions, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Review of available evidence shows that cutaneous adverse reactions occur with all commonly used antiosteoporotic agents. Notably, there are reports of SJS and TEN for bisphosphonates, and of DRESS and TEN for strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases).

Conclusion

With early recognition and proper management, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization and rehydration and systemic corticosteroids if necessary, the prognosis is good.

Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356:1255–59CrossRefPubMed

Hunziker T, Kunzi UP, Braunschweig S, Zehnder D, Hoigne R (1997) Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey. Allergy 52:388–93CrossRefPubMed

Bigby M (2001) Rates of cutaneous reactions to drugs. Arch Dermatol 137:765–70PubMed

US Food and Drugs Administration (2009) Pharmapendium

Gomes ER, Demoly P (2005) Epidemiology of hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol 5:309–16CrossRefPubMed

Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CS, Wu JY, Chen YT (2005) HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 102:4134–39CrossRefPubMed

Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT (2004) Medical genetics: a marker for Stevens Johnson syndrome. Nature 428:486CrossRefPubMed

Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jagel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A (2008) HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358:568–79CrossRefPubMed

Mockenhaupt M (2007) Epidemiology and causes of severe cutaneous adverse reactions to drugs, pp 18–31

10.

Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, Chosidow O, Guillot I, Paradis V, Joly P, Crickx B, Ranger-Rogez S, Descamps V (2009) Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure. Arch Dermatol 145:67–72CrossRefPubMed

11.

Roujeau JC (2005) Clinical heterogeneity of drug hypersensitivity. Toxicology 209:123–29CrossRefPubMed

12.

Svensson CK, Cowen EW, Gaspari AA (2001) Cutaneous drug reactions. Pharmacol Rev 53:357–79PubMed

13.

Aberer W, Kranke B (2008) Clinical manifestations and mechanisms of skin reactions after systemic drug administration. Drug Discovery Today 5:e237–e247CrossRef

14.

Valeyrie-Allanore L, Sassolas B, Roujeau JC (2007) Drug-induced skin, nail and hair disorders. Drug Saf 30:1011–30CrossRefPubMed

15.

Morison WL (2004) Clinical practice. Photosensitivity. N Engl J Med 350:1111–17CrossRefPubMed

16.

Wolf R, Orion E, Marcos B, Matz H (2005) Life-threatening acute adverse cutaneous drug reactions. Clin Dermatol 23:171–81CrossRefPubMed

17.

Bocquet H, Bagot M, Roujeau JC (1996) Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS). Semin Cutan Med Surg 15:250–257CrossRefPubMed

18.

Shiohara T, Takahashi R, Kano Y (2007) Drug-induced hypersensitivity syndrome and viral reactivation, pp. 251-266

19.

Borchers AT, Lee JL, Naguwa SM, Cheema GS, Gershwin ME (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis. Autoimmun Rev 7:598–605CrossRefPubMed

20.

Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, Sidoroff A, Schneck J, Roujeau JC, Flahault A (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 128:35–44CrossRefPubMed

21.

Ghislain PD, Roujeau JC (2002) Treatment of severe drug reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity syndrome. Dermatol Online J 8:5PubMed

22.

Allanore L, Roujeau JC (2007) Clinic and pathogenesis of severe bullous skin reactions: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, pp. 267–277

23.

Shiohara T, Inaoka M, Kano Y (2006) Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 55:1–8CrossRefPubMed

24.

Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker T, Saurat JH, Tschopp J, French LE (1998) Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 282:490–493CrossRefPubMed

25.

Faye O, Roujeau JC (2005) Treatment of epidermal necrolysis with high-dose intravenous immunoglobulins (IV Ig): clinical experience to date. Drugs 65:2085–90CrossRefPubMed

26.

European Medicines Agency (2008) Alendronate. Summary of product characteristics

27.

Kimura M, Kawada A, Murayama Y, Murayama M (2003) Drug eruption due to alendronate sodium hydrate. Contact Dermatitis 48:116CrossRefPubMed

28.

Kontoleon P, Ilias I, Stavropoulos PG, Papapetrou PD (2000) Urticaria after administration of alendronate. Acta Derm Venereol 80:398PubMed

29.

Biswas PN, Wilton LV, Shakir SA (2003) Pharmacovigilance study of alendronate in England. Osteoporos Int 14:507–14CrossRefPubMed

30.

High WA, Cohen JB, Wetherington W, Cockerell CJ (2003) Superficial gyrate erythema as a cutaneous reaction to alendronate for osteoporosis. J Am Acad Dermatol 48:945–46CrossRefPubMed

31.

Brinkmeier T, Kugler K, Lepoittevin JP, Frosch PJ (2007) Adverse cutaneous drug reaction to alendronate. Contact Dermatitis 57:123–25CrossRefPubMed

32.

Lazarov A, Moss K, Plosk N, Cordoba M, Baitelman L (2002) Alendronate-induced lichen planus. Isr Med Assoc J 4:389–90PubMed

33.

US Food and Drugs Administration (2002) Risedronate. Description

34.

(2009) Vidal 2009. Le Dictionnaire, 85th ed

35.

Barrera BA, Wilton L, Harris S, Shakir SA (2005) Prescription-event monitoring study on 13, 164 patients prescribed risedronate in primary care in England. Osteoporos Int 16:1989–98CrossRefPubMed

36.

Belhadjali H, Slim R, Aouam K, Youssef M, Zili J (2008) Cutaneous vasculitis induced by risedronate. Allergy 63:1405CrossRefPubMed

37.

European Medicines Agency (2007) Ibandronate. Summary of product characteristics

38.

European Medicines Agency (2008) Zoledronic acid. Summary of product characteristics

39.

Rizos EC, Milionis HJ, Elisaf MS (2006) Fever with rash following zolendronic acid administration. Clin Exp Rheumatol 24:455PubMed

40.

European Medicines Agency (2008) Strontium ranelate. Summary of product characteristics

41.

Groves C (2008) Interstitial granulomatous reaction to strontium ranelate. Arch Dermatol 144:268–69CrossRefPubMed

42.

Boada A, Carrascosa J, Leal L, Ferrandiz C (2009) Generalized cutaneous drug eruption due to strontium ranelate. J Eur Acad Dermatol Venereol 0 (in press)

43.

Pernicova I, Middleton ET, Aye M (2008) Rash, strontium ranelate and DRESS syndrome put into perspective. European Medicine Agency on the alert. Osteoporos Int 19:1811–12CrossRefPubMed

44.

Jonville-Bera AP, Crickx B, Aaron L, Hartingh I, utret-Leca E (2009) Strontium ranelate-induced DRESS syndrome: first two case reports. Allergy

45.

Lee HY, Lie D, Lim KS, Thirumoorthy T, Pang SM (2009) Strontium ranelate-induced toxic epidermal necrolysis in a patient with post-menopausal osteoporosis. Osteoporos Int 20:161–62CrossRefPubMed

46.

Grosso A, Douglas I, Hingorani A, MacAllister R, Smeeth L (2008) Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions. Br J Clin Pharmacol 66:689–94PubMed

47.

European Medicines Agency (2008) Raloxifene. Summary of product characteristics

48.

Layton D, Clarke A, Wilton LV, Shakir SA (2005) Safety profile of raloxifene as used in general practice in England: results of a prescription-event monitoring study. Osteoporos Int 16:490–500CrossRefPubMed

49.

European Medicines Agency (2008) Teriparatide. Summary of product characteristics

50.

European Medicines Agency (2007) Parathyroid hormone. Summary of product characteristics

51.

Burnett-Bowie SA (2008) Is twice-yearly denosumab beneficial in postmenopausal women with osteopenia but no history of fracture? Nat Clin Pract Endocrinol Metab 4:660–661CrossRefPubMed

52.

McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–31CrossRefPubMed

53.

Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–82CrossRefPubMed

54.

Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 301:513–21CrossRefPubMed

55.

Schnyder B, Pichler WJ (2009) Mechanisms of drug-induced allergy. Mayo Clin Proc 84:268–72CrossRefPubMed

Title: Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity
Authors: P. Musette
M. L. Brandi
P. Cacoub
J. M. Kaufman
R. Rizzoli
J.-Y. Reginster
Publication date: 01-05-2010
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 5/2010
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-009-1097-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity

Abstract

Summary

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2010

Prognosis of fracture: evaluation of predictive accuracy of the FRAX™ algorithm and Garvan nomogram

The need for a transparent, ethical, and successful relationship between academic scientists and the pharmaceutical industry: a view of the Group for the Respect of Ethics and Excellence in Science (GREES)

Transparency and trust

Neovascular AMD: an overlooked risk factor for injurious falls

Alveolar bone density measurement in risk assessment for bisphosphonate-related osteonecrosis of the jaw: response to comments by Taguchi

Elongated styloid process and atheroma in panoramic radiography and its relationship with systemic osteoporosis and osteopenia