Imatinib mesylate induces clinical remission in rheumatoid arthritis

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Letters to the editor / Joint Bone Spine 77 (2010) 366–375

Immunoelectrophoresis tests revealed a positive specific antibody against antigens from hydatid cyst fluid, double diffusion arc-5. Patient was treated effectively for his neuropathic pain with gabapentin. He was referred to the surgery department to be operated for a hydatid cyst of the left iliacus muscle.

Mondhor Golli Fattouma Bourguiba University Hospital, Tunisia ∗ Corresponding

author. E-mail address: [email protected] (A. Jellad). 18 March 2010

2. Discussion Isolated femoral neuropathy is uncommon and usually of compressive etiology such as hematoma (anticoagulant therapy, hemophilia), bursitis or rarely hydatid cyst of the iliopsoas muscle [1,2]. Hydatidosis is human disease caused by the larval from of Taenia echinococcus, which lives in the gut of the dog, wild canines and other carnivorous animals. They represent the definitive host. Humans become the accidental intermediate hosts by ingesting Taenia eggs. This disease is endemic in many countries where sheep, dogs and man live in close contact as North Africa [3]. The psoas location is characterized by clinical latency. The cyst is slow growing and remains asymptomatic for long period [4]. Signs of femoral nerve palsy rapidly develop after the onset of pain, together with a diminished patellar reflex. The ultrasonography is highly efficient in detecting germinal vesicles in cystic lesions. CT is performed in cases with indeterminate sonographic findings or negative immunological tests [5]. Ultrasonography and CT have a major interest in case of hydatid cyst of the psoas muscle [6,7]. Sometimes meticulous biopsy is necessary to confirm the diagnosis [8]. Surgery is the mainstay of treatment of hydatid cysts. Complete excision of the cysts represents the correct procedure [9]. Medical treatment as albendazole therapy provides a good alternative to surgery when several lesions are present, in cases of cyst rupture or to prevent complications such anaphylaxis and/or secondary echinococcosis [10]. Conflict of interest statement There is no conflict of interest with this work. References [1] Dauty M, Sigaud M, Trossaërt M, et al. Iliopsoas hematoma in patients with hemophilia: a single-center study. Joint Bone Spine 2007;74:179–83. [2] Erc¸etin C, Tükenmez M, Dural C, et al. Primary retroperitoneal hydatid disease mimicking retroperitoneal malignant tumor. Int J Infect Dis 2008;12:402–5. [3] Aoun K, Benabid M, Galai Y, et al. The current risk factors for hydatidosis in Tunisia. Med Trop 2009;69:311. [4] Feki W, Ghozzi S, Khiari R, et al. Multiple unusual locations of hydatid cysts including bladder, psoas muscle and liver. Parasitol Int 2008;57: 83–6. [5] Orhan Z, Kara H, Tuzuner T, et al. Primary subcutaneous cyst hydatic disease in proximal thigh: an unusual localisation: a case report. BMC Musculoskelet Disord 2003;4:25. [6] Pedrosa I, Saíz A, Arrazola J, et al. Hydatid disease: radiologic and pathologic features and complications. Radiographics 2000;20:795–817. [7] Garagnani L, Sudanese A, Rimondi E, et al. Primary hydatid cyst of the root of the thigh: a case report and review of the literature. Chir Organi Mov 2008;92:113–8. [8] Combalia A, Sastre-Solsona S. Hydatid cyst of gluteus muscle. Two cases. Review of the literature. Joint Bone Spine 2005;72:430–2. [9] Melis M, Marongiu L, Scintu F, et al. Primary hydatid cysts of psoas muscle. ANZ J Surg 2002;72:443–5. [10] Ntusi NA, Horsfall C. Severe disseminated hydatid disease successfully treated medically with prolonged administration of albendazole. QJM 2008;101:745–6.

Anis Jellad ∗ Soumaya Boudokhane Salem Ezzine Zohra Ben Salah

Available online 15 May 2010 doi:10.1016/j.jbspin.2010.03.016

Imatinib mesylate induces clinical remission in rheumatoid arthritis Keywords: Imatinib mesylate Rheumatoid arthritis Chronic myeloid leukaemia Treatment

Imatinib mesylate (imatinib) is a relatively specific inhibitor of the platelet-derived growth factor (PDGF) receptor tyrosine kinase that is widely used to treat chronic myeloid leukaemia (CML) and gastrointestinal stromal tumor [1]. It is able to inhibit rat adjuvantinduced arthritis and interfere in multiple signal transduction pathways implicated in rheumatoid arthritis (RA) pathogenesis, including mast cell c-Kit signaling. It also lowers TNF-alpha and other cytokines production [2–4]. Additionally, the inhibition of PDGF-receptor signaling by the drug reduces the proliferation of synovial fibroblasts (FLS) [3]. Some previous published reports suggest the efficacy of imatinib use in RA [5–9]. Here, we describe the case of a 53-yearold woman with RA for 11 years. She had severe polyarthritis involving proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints, wrists, elbows, shoulders, hips, knees, ankles and metatarsophalangeal (MTP) joints. Laboratory tests showed rheumatoid factor of 350 IU/ml (normal 0–15 IU/ml), C-reactive protein (CRP) 14 mg/l and erythrocyte sedimentation rate (ESR) 53 mm/1st hour. Disease activity score (DAS) 28 was 5.53. She was initially treated with methotrexate (MTX) 15 mg per oral once a week and then was increased to 25 mg subcutaneously (SC), without response. Leflunomide 20 mg/day was added, but she also had no response. Then she received TNF blocker infliximab (IFX) 3 mg/kg plus MTX 25 mg/week with some efficacy, but after getting response she needed to change IFX to adalimumab 40 mg every other week SC due to infusion reaction to IFX. She was being treated for 3 years with adalimumab when she developed intense leukocytosis (blood cell count: hematocrit = 46.8%; hemoglobin = 15.4; leukocytes = 56,100; segmented = 53% band = 2%; metamyelocyte = 5%; myelocyte = 16%). Bone marrow aspirate and cytogenetic studies confirmed the diagnosis of CML with the typical Philadelphia chromosome. After having been diagnosed with CML, MTX and adalimumab were immediately discontinued. She was initially treated for CML with hydroxyurea for cytoreduction, followed by imatinib 400 mg orally once a day, when she got important improvement of blood cell counts. She tolerated imatinib, but had mild nausea and edema of the lower extremities. After starting imatinib, without concomitant DMARDs, corticosteroids or biologic agents, her symptoms and signs of RA rapidly improved and after 6 months she got clinical remission, with absence of pain, swollen and tender joints, CRP = 1.84 mg/l, ESR = 2 mm and DAS 28 = 0.51. This excellent response of leukaemia and RA continues for 21 months whereas using only imatinib.

Letters to the editor / Joint Bone Spine 77 (2010) 366–375 Table 1 Studies available on protein tyrosine kinases inhibitors in rheumatoid arthritis (RA) treatment. Drug

Study Design

Imatinib Imatinib Imatinib Imatinib

Case report Case report Open label Protocol amended [6]

Imatinib Masitinib a

Case report Open label

n

CML

Response

Follow up

Reference

Yes Yes No No

Complete Complete Improvement 2-withdrew

2 months 17 months 3 months 24 months

[5] [7] [6] [8]

1 Yes 43a No

1-improved Complete Improvement

1 1 3a 3a

E-mail address: fi[email protected] (S. Fialho). 23 March 2010 Available online 15 May 2010 doi:10.1016/j.jbspin.2010.03.014

Adult onset Still’s disease following influenza vaccination – 84 weeks

[9] [10]

Refractory to DMARDs.

Imatinib reduces the incidence and severity of collagen induced arthritis and some cases of RA have been successfully treated with imatinib, such as in our patient [5–9]. Table 1 briefly summarizes studies available so far on protein tyrosine kinases inhibitors in the treatment of RA. Our case report confirms the excellent response of RA with tyrosine kinase inhibition by imatinib and suggests that clinical trials with the drug should be done in severe RA patients refractory to DMARDs or biologic agents. Conflict of interest statement None of the authors has any conflicts of interest to declare. References [1] Almeida A, Castro I, Coutinho J, et al. Recommendations for diagnosis, treatment and monitoring of chronic myeloid leukemia. Acta Med Port 2009;22: 537–44. [2] Koyama K, Hatsushika K, Ando T, et al. Imatinib mesylate both prevents and treats the arthritis induced by type II collagen antibody in mice. Mod Rheumatol 2007;17:306–10. [3] Terabe F, Kitano M, Kawai M, et al. Imatinib mesylate inhibited rat adjuvant arthritis and PDGF-dependent growth of synovial fibroblast via interference with the Akt signaling pathway. Mod Rheumatol 2009;19: 522–9. [4] Juurikivi A, Sandler C, Lindstedt KA, et al. Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis. Ann Rheum Dis 2005;64:1126–31. [5] Miyachi K, Ihara A, Hankins RW, et al. Efficacy of imatinib mesylate (STI571) treatment for a patient with rheumatoid arthritis developing chronic myelogenous leukemia. Clin Rheumatol 2003;22:329–32. [6] Eklund KK, Joensuu H. Treatment of rheumatoid arthritis with imatinib mesylate: clinical improvement in three refractory cases. Ann Med 2003;35: 362–7. [7] Ames PR, Aye WW, Beatty C, et al. Imatinib treatment of seropositive arthritis in a young woman with chronic myeloid leukemia. J Rheumatol 2008;35:1682. [8] Eklund KK, Lindstedt K, Sandler C, et al. Maintained efficacy of the tyrosine kinase inhibitor imatinib mesylate in a patient with rheumatoid arthritis. J Clin Rheumatol 2008;14:294–6. [9] Vernon MR, Pearson L, Atallah E. Resolution of rheumatoid arthritis symptoms with imatinib mesylate. J Clin Rheumatol 2009;15:267. [10] Tebib J, Mariette X, Bourgeois P, et al. Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study. Arthritis Res Ther 2009;11:R95.

Ivânio Pereira a Sonia Fialho b,∗ Gláucio Castro b Adriana Zimmermann b a Rheumatology section, University Hospital of the Federal University of Santa Catarina, Virgílio Várzea, 1510, Bloco H 101, Florianópolis-SC, Brazil 88032-001 b Rheumatology section, University Hospital of the Federal University of Santa Catarina, Florianópolis-SC, Brazil ∗ Corresponding

373

author. Tel.: +55 48 37334635; fax: +55 48 37334635.

Keywords: Arthritis Infection Influenza Vaccination

Although there is no conclusive evidence for the causal link between influenza vaccination and rheumatic diseases, many case reports have been demonstrated. To our knowledge, however, adult onset Still’s disease (AOSD) after influenza vaccination has not previously been reported in the English literature. We present firstly here a case of patient with AOSD, developed following influenza vaccination. A 73-year-old woman, who had no specific past medical history, developed daily high spiking fever (up to 39.5 ◦ C), sore throat and polyarthritis of both hand, wrist and knee joints without skin rash two days after receiving 0.5 mL of inactivated influenza vaccine (Influenza3; SK, South Korea). Laboratory examination revealed WBC of 16,000/mm3 , CRP of 125.7 mg/L (normal range: < 5 mg/L) and ESR of 88 mm/h. Serum ferritin level was increased, more than 2,000 ng/mL (normal range: 15–150 ng/mL). ANA, RF, tests for autoantibodies and antibodies against viral infections were negative. Bacterial and viral cultures from a throat swab, blood and urine grew no pathogenic organisms. Chest radiographs showed both pleural effusion. Based on these findings, a diagnosis of AOSD was made according to the classification criteria [1]. She was successfully managed with prednisolone, non-steroidal anti-inflammatory drug, methotrexate and hydroxychloroquine. Although the etiology of AOSD remains unknown, it has been proposed that infections can trigger the interplay between genetic factors, immune disarray, and pathogenic antigens [2,3]. Several infectious organisms were suggested as a triggering factor in the etiopathogenesis of AOSD, which include influenza A, parvovirus B19, cytomegalovirus, parainfluenza, rubella, coxsackie B4 [3–5]. Based on these assumptions, it was possible to speculate a pivotal role of viral proteins by vaccination in developing AOSD. However, there were no reports of AOSD after vaccination until now. Although the relationship between AOSD and influenza vaccination is not known, previous reports suggest the possible role of influenza vaccination in the etiology of AOSD. There is some recent evidence suggesting association between influenza infection and autoimmune diseases [6]. On reviewing the literature from the Committee of Safety of Medicines in the period 1963–1994, there were 11 cases of arthralgia, six cases of arthritis and one case of reactive arthritis [7]. The relationship between influenza vaccination and the occurrence of rheumatic diseases, including Henoch–Schoenlein purpura, rheumatoid vasculitis, microscopic polyangiitis and reactive arthritis, also has been suggested [8]. However, the exact mechanisms were not well known. One possible mechanism is that infection may trigger cyclical episodes of abrupt overactivity of the inflammatory machinery as autoinflammatory syndrome [9]. Several mechanisms also have been claimed to account for the development of autoimmune disease after vaccination, molecular mimicry, induction of synthesis of autoantibodies, production of cytokines following immunization and effects on the TH1/TH2 lymphocyte balance [8,10]. Further reports and