Methotrexate Osteopathy in a Patient with Rheumatoid Arthritis
Transkript
Methotrexate Osteopathy in a Patient with Rheumatoid Arthritis
OLGU SUNUMU Methotrexate Osteopathy in a Patient with Rheumatoid Arthritis: Case Report Tuba YILDIRIM GÜNAY,a Yeşim GARİP,b Hatice BODURc a Clinic of Physical Medicine and Rehabilitation, İskenderun State Hospital, Hatay, b Clinic of Physical Medicine and Rehabilitation Private Başak Medical Center, c Clinic of Physical Medicine and Rehabilitation Ankara Numune Training and Research Hospital, Ankara Geliş Tarihi/Received: 06.05.2014 Kabul Tarihi/Accepted: 19.08.2014 This abstract was presented at Congress of Excellence in Rheumatology (25-28 Ocak 2012, İspanya- Madrid)’. [Gunay T, Garip Y, Bodur H, ‘‘Methotrexate osteopathy in a patient with rheumatoid arthritis’’, Excellence in Rheumatology, Rheumatology (Oxford) volume 51 supplement 2 January 2012, ii5 (PP33), Madrid, 25-28 January 2012] Yazışma Adresi/Correspondence: Yeşim GARİP Private Başak Medical Center, Clinic of Physical Medicine and Rehabilitation, Ankara, TÜRKİYE/TURKEY dryesimgarip@gmail.com ABSTRACT Methotrexate (MTX) is an anti-metabolite frequently used in the treatment of autoimmune conditions such as rheumatoid arthritis (RA) and psoriatic arthritis. Long-term use of MTX is associated with various potential side effects. In rare circumstances, it may lead to osteopathy, which is characterized by bone pain, osteoporosis and fractures. Herein, a 69-year-old woman female patient who was receiving low dose MTX for RA and admitted to our outpatient clinic with complaints of swelling of the right leg and ankle and metatarsalgia aggravated with weight-bearing is presented. In physical examination of the patient, right ankle, fourth and fifth metatarsophalangeal joints were swollen, painful and tender to palpation. Laboratory parameters including complete blood count, erythrocyte sedimentation rate, c-reactive protein, serum total calcium, phosphorus, 25-hydroxy vitamin D3, parathyroid hormone, alkaline phosphatase were in normal ranges. In radiographic examination, fifth metatarsal fracture was observed. This finding was confirmed with computed tomography. The bone mineral density (BMD) results, measured by dual energy x-ray absorptiometry, were as follows; lumbar spine BMD T-score: -2.2, femoral neck BMD T-score: -2.2. The patient was diagnosed with MTX osteopathy due to long-term MTX therapy. Symptoms were resolved when MTX was discontinued. In case of joint pain and swelling, inconsistent with disease activity in patients who are on long-term MTX therapy, osteopathy, which is characterized with a triad of bone pain, osteoporosis and fractures should be kept in mind. Key Words: Rheumatoid arthritis; methotrexate (MTX) ÖZET Metotreksat (MTX), romatoid artrit (RA) ve psöriyatik artrit gibi otoimmün hastalıkların tedavisinde sıklıkla kullanılan bir anti-metabolittir. Uzun dönem MTX kullanımı bir çok potansiyel yan etkiyle ilişkilidir. Nadir durumlarda kemik ağrısı, osteoporoz ve kırıklarla karakterize olan osteopatiye yol açabilir. Burada, RA tanısı ile MTX tedavisi alan ve sağ bacakta ve ayak bileğinde şişlik ve yüklenme ile artan metatarsalji şikayetleri ile polikliniğimize başvuran 69 yaşında bir kadın hasta sunulmuştur. Hastanın fiziksel muayenesinde, sağ ayak bileği, dördüncü ve beşinci metatatarsofalangeal eklemler şiş, ağrılı ve palpasyonla hassastı. Tam kan sayımı, eritrosit sedimentasyon hızı, c-reaktif protein, serum total kalsiyum, fosfor, 25-hidroksi vitamin D3, paratiroid hormon, alkalen fosfataz değerleri normal sınırlardaydı. Radyografik incelemede 5. metatarsal kırığı gözlendi. Bu bulgu, bilgisayarlı tomografi ile doğrulandı. Dual enerji x-ışını absorbsiyometrisi ile ölçülen kemik mineral dansitesi (KMD) sonuçları; lomber omurga KMD T-skoru: -2,2, femur boyun KMD T-skoru: -2,2 idi. Hastaya uzun dönem MTX tedavisine bağlı MTX osteopatisi tanısı kondu. Semptomlar MTX kesildiği zaman geriledi. Hastalık aktivitesi ile uyumlu olmayan eklem ağrısı ve eklem şişliği varlığında, uzun süreli MTX tedavisi alanlarda, ayırıcı tanıda, kemik ağrısı, osteoporoz ve kırık triadı ile karakterize osteopati akılda tutulmalıdır. Anahtar Kelimeler: Romatoid artrit; metotreksat (MTX) M Romatol Tıp Rehab 2014;25(2):42-4 Copyright © 2014 by Türk Tıbbi Rehabilitasyon Kurumu Derneği 42 TX is a structural analogue of folic acid, which is commonly used in high doses for the treatment of malignancies, and in lower doses over prolonged periods for the treatment of RA and various Romatol Tıp Rehab 2014;25(2) METHOTREXATE OSTEOPATHY IN A PATIENT WITH RHEUMATOID ARTHRITIS: CASE REPORT inflammatory diseases. It may lead to osteopathy which is characterized by a triad of bone pain, osteoporosis and insufficiency fractures.1 Herein we report a patient who was receiving MTX for RA presenting with metatarsal stress fracture. CASE REPORT A 69-year-old woman with rheumatoid arthritis on long-term MTX therapy was referred to our outpatient clinic with swelling of the right leg and ankle and metatarsalgia aggravated with weight-bearing. Her complaints had persisted for 15 days. In her past medical history, she had been diagnosed with RA for 15 years and received MTX up to 20 mg/week for the past 12 years. She had been treated with prednisolone 7.5 mg daily for a year in the beginning of her disease, but prednisolone had been discontinued because of gastrointestinal side effects. She had no history of trauma or osteoporotic or insufficiency fractures. She was postmenopausal and non-smoker. Tuba YILDIRIM GÜNAY et al. lowing: erythrocyte sedimentation rate (ESR) 20 mm/h (normal range: 0-20 mm/h), C-reactive protein (CRP) 1.5 mg/L (normal range: 0,00-5.00 mg/L), serum total calcium 9.3 mg/dL (normal range: 8.510.6 mg/dL), serum ionized calcium 4.5 (normal range: 4.5-5.2mg/dL), serum phosphorus 4.7 mg/dL (normal range: 2.4-4.7 mg/dL), 25-hydroxy vitamin D3 32.2 ng/ml (6.3-46.4 ng/ml), parathyroid hormone (PTH) 6 pmol/L (normal range:1.3-9.3 pmol/L ), alkaline phosphatase 72 u/L (normal range: 32-91 u/L). Thyroid function tests were normal. Radiographs performed eight months later revealed an old fifth metatarsal fracture (Figure 1 and 2). This was confirmed with computed tomography (CT). CT findings included the following: soft-tissue swelling, old fracture of the fifth metatarsal bone with plantar displacement of the fracture fragment and periosteal reaction. The bone mineral density results measured by dual energy x-ray absorptiometry were as follows; lumbar spine BMD Tscore: -2.2, femoral neck BMD T-score: -2.2. In physical examination, the range of motion of her ankle was normal. Right ankle, fourth and fifth metatarsophalangeal joints were swollen, painful and tender to palpation. Disease Activity Score- 28 (DAS28) was 3.36 (moderate disease activity). Radiographs of right ankle and foot were normal, showed no evidence of stress fracture. She was diagnosed with MTX osteopathy due to long-term MTX therapy. Bone pain was resolved when MTX was discontinued, but the tenderness of right ankle and fifth metatarsal persisted for about one month. Complete blood count and serum biochemistry was normal. Laboratory parameters showed the fol- MTX osteopathy is rare and its diagnosis is based on characteristic clinical and radiographic features. FIGURE 1: Anteroposterior view of right foot showing 5th metatarsal fracture. FIGURE 2: Lateral view of right foot. Romatol Tıp Rehab 2014;25(2) DISCUSSION 43 Tuba YILDIRIM GÜNAY et al. METHOTREXATE OSTEOPATHY IN A PATIENT WITH RHEUMATOID ARTHRITIS: CASE REPORT It is characterized by severe lower extremity pain and by osteoporosis particularly involving the lower extremities. Radiographs usually show osteoporosis, fractures and thick dense provisional zones of calcification and growth arrest lines resembling scurvy. Calcium phosphorus metabolism is mostly within the normal ranges. When MTX is discontinued, the fractures usually heal.1,2 It was first reported in children with childhood leukemia treated with high-dose MTX in 1970 by Ragab et al.3 Similarly, O’Regan S and Stanisavljevic reported osteopathy due to high-dose MTX in children with leukaemia.4,5 Similar clinical features were reported in patients with inflammatory arthritis on low-dose MTX therapy.6-10 Preston reported a 58 year old woman with stress fracture while receiving low weekly doses of MTX.6 Initial radiographs of ankles showed a sclerosis area at the distal left metaphysis. Radi- 1. 2. 3. 4. 5. 44 Koller A, Fill H, Kurz R, Riccabona G, Haas H. Osteopathy due to methotrexate. Osterr Z Onkol 1976;3(3):63-9. Schwartz AM, Leonidas JC. Methotrexate osteopathy. Skeletal Radiol 1984;11(1):13-6. Ragab AH, Frech RS, Vietti TJ. Osteoporotic fractures secondary to methotrexate therapy of acute leukaemia in remission. Cancer 1970;25(3):580-5. O'Regan S, Melhorn DK, Newman AJ. Methotrexate induced bone pain in childhood leukaemia. Am J Dis Child 1973;126(4):48990. Stanisavljevic S, Babcock A L. Fractures in children treated with methotrexate for ographs performed six months later showed bilateral distal tibial fractures and a proximal left tibial fracture. Similarly in our case, initial radiographs were normal. Radiographs performed eight months later demonstrated fifth metatarsal fracture. Mechanism of impaired bone formation during low dose MTX therapy is not very well known. The results of metabolic studies showed an increased bone resorption in patients receiving MTX.11 On the other hand, Uehara reported that MTX suppressed bone formation by inhibiting differentiation of early osteoblastic cells.12 In conclusion, it is important that physician should be aware of this complication in patients receiving MTX, because symptoms may easily be confused with synovitis. Long term therapy with MTX could be an extra risk factor for fractures in RA patients receiving corticosteroids and in elderly patients with senile osteoporosis. REFERENCES 6. 7. 8. 9. leukaemia. Clin Orthop Relat Res 1977;(125): 139-44. Preston SJ, Diamond T, Scott A, Laurent MR. Methotrexate osteopathy in rheumatic disease. Ann Rheum Dis 1993;52(8):582-5. Zonneveld IM, Bakker WK, Dijkstra PF, Bos JD, van Soesbergen RM, Dinant HJ. Methotrexate osteopathy in long-term, lowdose methotrexate treatment for psoriasis and rheumatoid arthritis. Arch Dermatol 1996; 132(2):184-7. Maenaut K, Westhovens R, Dequeker J. Methotrexate osteopathy, does it exist? J Rheumatol 1996;23(12):2156-9. Rudler M, Pouchot J, Paycha F, Gentelle S, Grasland A, Vinceneux P. Low dose methotrexate osteopathy in a patient with polyarticular juvenile idiopathic arthritis. Ann Rheum Dis 2003;62(6):588-9. 10. van der Bijl AE, Zijlstra TR, Engelage AH, Posthuma BJ, van Veen GJ. [Three patients with a fracture during methotrexate use, possibly due to methotrexate osteopathy.] Ned Tijdschr Geneeskd 2008;152(43):235760. 11. Nevinny HB, Krant MJ, Moore EW. Metabolic studıes of the effects of Methotrexate. Metabolism 1965;14:135-40. 12. Uehara R, Suzuki Y, Ichikawa Y. Methotrexate (MTX) inhibits osteoblastic differentiation in vitro: possible mechanism of MTX osteopathy. J Rheumatol 2001;28(2):251-6. Romatol Tıp Rehab 2014;25(2)