International Journal of Rheumatic Diseases 2015; 18: 466–469

APLAR GRAND ROUND CASE

Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthritis Ozlem YILMAZ TASDELEN,1 Fatma Gul YURDAKUL,1 Semra DURAN2 and Hatice BODUR1 1 Departments of Physical Medicine and Rehabilitation, and 2Radiology, Ankara Numune Training and Research Hospital, Ankara, Turkey

Abstract Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of isotretinoin is transient muscle and/or joint pains. Here, we report a case with bilateral wrist and metacarpophalangeal joint arthritis and unilateral sacroiliitis associated with isotretinoin usage to attract attention, particularly from physiatrists, rheumatologists and dermatologists, to this rare adverse effect of isotretinoin. Key words: acne, arthritis, isotretinoin, retinoid, sacroiliitis.

INTRODUCTION Isotretinoin is a synthetic vitamin A derivative that is used for the treatment of severe acne that is resistant to other treatments. Isotretinoin has adverse skeletal and rheumatologic effects. Unilateral or bilateral sacroiliitis associated with isotretinoin usage is well known due to recently reported cases1–7. Isotretinoin-induced peripheral arthritis has also been reported8–13. Primarily, large joint involvements have been described in these reports. We report a case of a young male patient who developed bilateral wrist and metacarpophalangial (MCP) arthritis and subsequent unilateral sacroiliitis during the administration of isotretinoin for cystic acne lesions.

CASE REPORT A 23-year-old male patient presented with complaints of pain in his wrists and in five metacarpophalangial (MCP) joints on both sides lasting for 2 weeks. He had no myalgia, arthralgia of any other joints or low back

Correspondence: Ozlem Yilmaz Tasdelen, MD, (physiatrist), Gayret M. Oruc Reis S. TOKI Park Ciftlik Konutlari BK4 No: 11 Yenimahalle Ankara, Turkey. Email: [email protected]

pain. Neither he nor his family members had any rheumatologic diseases. He did not report any significant trauma. He had no histories of recent genitourinary, gastrointestinal or respiratory infections. He complained of morning stiffness in his hands that lasted for more than an hour. His wrists and all of his MCP joints were swollen and his wrists were warm. The remaining joints, spine and his general physical examination were normal. A complete blood count and serum biochemistry were also normal. C-reactive protein (CRP) levels were high at 1.7 mg/dL (0–1 mg/dL). The patient’s erythrocyte sedimentation rate (ESR) was 15 mm/h. Rheumatoid factor, anti-cyclic citrulinated peptide (CCP) antibodies, anti-nuclear antibodies (ANA), antidouble-stranded DNA, Brucella agglutination test and serologic tests for hepatitis B and C were all negative. Thyroid function tests and urine analysis were normal. Radiographs of the hands revealed only soft tissue swelling. He was not on any medication other than isotretinoin, which he had been using for cystic acne on his face and back for 6 months (initial dose 20 mg/day for the first 4 months, which was subsequently increased to 40 mg/day for the next 2 months). He was diagnosed with isotretinoin-induced arthritis and 75 mg/day indomethacine was administered. On the fifth day of indomethacine administration, the arthritic wrist swellings dissipated, but the tenderness of the

© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

Isotretinoin-induced arthritis

Figure 1 Hyperintense signal change in the inferior portion of the left sacroiliac joint (short tau inversion recovery [STIR] sequence, coronal image).

wrists and the MCP joints persisted, and the CRP levels rose to 2.7 mg/dL. The Naranjo14 adverse drug reactions probability scale score was calculated as six, which indicated a probable relationship. Isotretinoin was ceased, and the indomethacine dose was increased to 150 mg/day. After 6 weeks, the symptoms had completely resolved, and laboratory results were normal. Indomethacine was stopped, but he again presented with swollen wrists and additional inflammatory low back pain after 2 weeks. Mennel and Gaenslen

Figure 2 Normal findings on magnetic resonance imaging of the left sacroiliac joint (short tau inversion recovery [STIR] sequence, coronal image).

International Journal of Rheumatic Diseases 2015; 18: 466–469

tests were positive on the left side. The ESR was 1 mm/h, CRP was 9.45 mg/L (0–5 mg/L) and human leukocyte antigen (HLA)-B27 was negative. Magnetic resonance imaging (MRI) revealed active inflammatory sacroiliitis of the left sacroiliac joint (Fig. 1). A treatment of 750 mg/day naproxen sodium was initiated. Ten days later, the patient’s low back pain had nearly completely resolved, but the swelling of the wrist joints persisted. Ten milligrams per day prednisolone and 2 g/day sulfasalazine were added to the treatment. The synovitis resolved quickly, the prednisolone was stopped gradually over 6 weeks, but the sulfasalazine was continued for 6 months. He was asymptomatic for this period. A repeated MRI performed after 6 months from the first MRI revealed no evidence of sacroiliitis, no effusion, no synovitis and no abnormal bone marrow signals (Fig. 2). The sulfasalazine was subsequently stopped. No recurrence was observed within 6 months.

DISCUSSION The most frequent rheumatologic side effects of retinoids are musculoskeletal pain and arthralgias, which occur in approximately 20% of patients. Typically, these side effects are mild and disappear when the treatment is stopped.15 Arthritis is an uncommon rheumatologic side effect of isotretinoin. Our patient is the first case to initially exhibit bilateral involvement of the wrists and MCP joints resembling rheumatoid arthritis and later exhibit acute sacroiliitis-like axial spondyloarthritis. Typically mono- or oligo-arthritis is observed, and the most frequently involved joint is the knee joint among the reported cases in the literature. Pedraz13 reported arthritis of the hip, Matsuoka8 reported arthritis of the knee in two cases, Callot10 reported arthritis of the knee, and Duborg12 reported arthritis of the elbow in a boy. According to our knowledge, no cases of symmetric involvement of the wrists and MCP joints like that observed in our patient have been reported. The association between isotretinoin usage and sacroiliitis has been well described in recent years. The underlying mechanism is thought to be related to the detergent-like properties of isotretinoin that might induce liposomal membrane solubilization and cause the destruction of synovial cells and resulting arthritis.16 Some authors have discussed whether isotretinoin can cause sacroiliitis or whether it triggers sacroiliac inflammation in genetically susceptible persons.1,3,4,7 Our patient was HLA-B27 negative, his sacroiliac inflammation resolved with the discontinuation of isotretinoin and anti-inflammatory treatment, and the

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healing was proven with MRI. Thus, we believe that sacroiliitis was not triggered but rather induced by isotretinoin in our patient. Arthritis can accompany acne fulminans. This severe form of acne is characterised by ulcerous acne and systemic symptoms that include the osteoarticular system. Sacroiliac joint involvement has been reported to occur in approximately 21% of patients in whom arthritis accompanies acne fulminans.17 Our patient had nodulo-cystic acne rather than acne fulminans. The idea that non-radiographic axial spondyloarthropathy is an early stage of ankylosing spondylitis has recently changed. Patients with reactive arthritis can meet the Assessment in Ankylosing Spondylitis International Working Group axial spondyloarthropathy criteria,18 but the clinical features resolve spontaneously in a significant proportion of such patients.19 Our case also met the axial spondyloarthropathy criteria with the exception of the duration of inflammatory back pain, which was below 3 months; however, sacroiliitis was revealed on MRI. The patient had arthritis in his wrists and MCP joints. Although transient axial spondyloarthropathy was a possible diagnosis for our patient, the lack of genitourinary, gastrointestinal or any other infectious disease history decreases the likelihood that reactive arthritis was present. Arthritis and sacroiliitis induced by isotretinoin are typically self-limited and resolve within a few weeks or months with non-steroidal anti-inflammatory drugs (NSAIDs). Yılmazer5 and Barbareschi3 treated patients with sacroiliitis with low-medium doses of oral steroids plus NSAID’s for 6 weeks to 1 year. Eksioglu,1 Dincer2 and Levinson5 treated patients with sacroiliitis with oral NSAIDs alone. These authors reported that their patients were symptom free within a few weeks. Isotretinoin-induced peripheral arthritis has mostly been treated by the withdrawal of isotretinoin and the administration of a NSAID for a few months in reported cases.8,10,12,13 Hudges9 added D-penicillamine to a NSAID plus oral prednisolone treatment for his patient with hip monoarthritis induced by isotretinoin and used this regimen for 10 months. We also used a synthetic disease-modifying anti-rheumatic drug, that is, sulfasalazine, in our patient. The arthritis in his hands resolved with indomethacine, but sacroiliitis was superimposed. He was treated with a low-dose steroid and sulfasalasine. Whether the sacroiliitis would have been observed if we had administered prednisolone with indomethacine at his first visit is unknown. Hyperosteosis of the spine and the appendicular bone, osteoporosis, spontaneous fractures, hypercalce-

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mia, hypercalciuria, muscle damage, muscle hypertonia and necrotizing vasculutis are other rare rheumatologic side effects of retinoids.15 In conclusion, doctors should be aware of this rare cause of acute arthritis in daily practice, and patients with acute arthritis or inflammatory low back pain should be asked about their medication usage.

REFERENCES 1 Eksioglu E, Oztekin F, Unlu E, Cakci A, Keyik B, Karadavut IK (2008) Sacroiliitis and polyneuropathy during isotretinoin treatment. Clin Exp Dermatol 33, 122–4. 2 Dincer U, Cakar E, Kiralp MZ, Dursun H (2008) Can isotretinoin induce sacroiliitis: three cases. Turk J Rheumatol 23, 157–9. 3 Rozin AP, Kagna O, Shiller Y (2010) Sacroiliitis and severe disability due to isotretinoin therapy. Rheumatol Int 30, 985–6. 4 Barbareschi M, Paresce E, Chiaratti A, Ferla Lodigiani A, Clerici G, Greppi F (2010) Unilateral sacroiliitis associated with systemic isotretinoin treatment. Int J Dermatol 49 (3), 331–3 5 Levinson M, Gibson A, Stephenson G (2012) Sacroiliitis secondary to isotretinoin. Australas J Dermatol 53, 298– 300. 6 Yılmazer B, Cosan F, Cefle A (2013) Bilateral acute sacroiliitis due to isotretinoin therapy: a case report. Int J Rheum Dis 16, 604–5. 7 Geller AS, Alagia RF (2013) Sacroiliitis after use of oral isotretinoin–association with acne fulminans or adverse effect? An Bras Dermatol 88(6 Suppl.1), 193–6. 8 Matsuoka LY, Wortsman J, Pepper JJ (1984) Acute arthritis during isotretinoin treatment for acne. Arch Intern Med 144, 1870–1. 9 Hughes RA (1993) Arthritis precipitated by isotretinoin treatment for acne vulgaris. J Rheumatol 20 (7), 1241–2. 10 Callot V, Ochonisky S, Vabres P, Revuz J (1994) Acute arthritis during isotretinoin treatment. Ann Dermatol Venereol 121, 402–3. 11 Bewley AP, Rankin EC, Levell NJ, Robinson TW (1995) Isotretinoin causing acute aseptic arthropathy. Clin Exp Dermatol 20, 279. 12 Dubourg G, Koeger AC, Huchet B, Rozenberg S, Bourgeois P (1996) Acute monoarthritis in a patient under isotretinoin. Rev Rhum Engl Ed 63, 228–9. 13 Pedraz T, Martınez A, Pascual E (2006) Acute hip monoarthritis in a patient treated with isotretinoin. J Clin Rheumatol 12, 105–6. 14 Naranjo CA, Busto U, Sellers EM et al. (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30, 239–45. 15 Kaplan G, Haettich B (1991) Rheumatological symptoms due to retinoids. Baillieres Clin Rheumatol 5, 77–97.

International Journal of Rheumatic Diseases 2015; 18: 466–469

Isotretinoin-induced arthritis

16 De Francesco V, Stinco G, Campanella M (1997) Acute arthritis during isotretinoin treatment for acne conglobate. Dermatology 194, 195. 17 Knitzer RH, Needleman BW (1991) Musculoskeletal syndromes associated with acne. Semin Arthritis Rheum 20, 247–55. 18 Rudwaleit M, van der Heijde D, Landewe R et al. (2009) The development of Assessment of SpondyloArthritis

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international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68, 777–83. 19 Robinson PC, Wordsworth BP, Reveille JD, Brown MA (2013) Axial spondyloarthritis: a new disease entity, not necessarily early ankylosing spondylitis. Ann Rheum Dis 72, 162–4.

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Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthritis.

Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of ...
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