Radiographic healing with sustained clinical remission in a patient with rheumatoid arthritis receiving methotrexate monotherapy.код для вставкиСкачать
ARTHRITIS & RHEUMATISM Vol. 46, No. 10, October 2002, pp 2804–2807 DOI 10.1002/art.10568 © 2002, American College of Rheumatology RADIOLOGIC VIGNETTE Radiographic Healing With Sustained Clinical Remission in a Patient With Rheumatoid Arthritis Receiving Methotrexate Monotherapy Siegfried Wassenberg and Rolf Rau The most important goal in the treatment of rheumatoid arthritis (RA) is to slow or even stop joint destruction. Investigators have often questioned whether radiographic improvement of joint damage actually occurs, but such improvement can provide direct evidence that the destructive process has been reversed. The recognition of reparative changes may become even more important with the availability and further development of more potent and faster-acting antirheumatic drugs. To date, reparative changes have been observed only with long-term monitoring of patients and when radiographs are obtained after profound clinical improvement or remission has been achieved. There may be a time lag of 6–12 months between the time clinical improvement has been achieved and the time improvement is evident radiographically. As a rule, patients have to be followed up for several years before radiographic repair can be recognized indisputably. The present case report with radiologic images demonstrates that remission and impressive repair of severely damaged joints may occur with conventional disease-modifying antirheumatic drug (DMARD) monotherapy (in this case, methotrexate [MTX]) as early as within 1 year of treatment initiation and that improvement may continue over several years. sulfasalazine was replaced by parenteral gold in April 1995. In August 1995, azathioprine (100 mg daily) was added to the gold salt regimen. At the time of first admission to the hospital in February 1997, the patient had persistent swelling of multiple joints of the hands, wrists, and forefeet. She reported early morning stiffness of ⬎30 minutes. The erythrocyte sedimentation rate (ESR) was elevated 39 mm/hour, and the C-reactive protein (CRP) level was 4.09 mg/dl. Rheumatoid factor had become weakly positive (28 IU/liter). Radiographs of the hands, wrists, and forefeet demonstrated severe destructive changes at both wrists and the second metacarpophalangeal (MCP) joints of both hands, and erosive changes at the left third proximal interphalangeal (PIP) joint and the third distal interphalangeal (DIP) joints on both sides; there were also large erosions at the first, third, and fifth metatarsophalangeal (MTP) joints of the left foot and the first, third, fourth, and fifth MTP joints of the right foot. The combined treatment with parenteral gold and azathioprine was switched to 15 mg MTX administered intramuscularly once a week without folic acid supplementation. In addition, the patient underwent inpatient treatment with rest, physiotherapy, occupational therapy, etc. During her hospital stay, the prednisolone dosage was reduced to 3 mg daily. Four months later, in July 1997, the daily prednisolone dosage was tapered to 1.5 mg. The number of swollen joints and intensity of the swelling had decreased significantly. The patient reported having no early morning stiffness. The ESR was 25 mm/hour, and the CRP level was 2.4 mg/dl. The MTX dosage and route of administration were changed to 20 mg orally/week. At followup in March 1998, 1 year after her first admission, the patient noted no problems with her joints. Prednisolone treatment had been stopped in September 1997. There was only minimal soft tissue swelling around the left third PIP joint. There was no joint tenderness. The mobility of all joints was completely normal. The patient was very active, performing Clinical course The patient developed typical symptoms of RA early in 1994, when she was 56 years old. The diagnosis of seronegative RA was confirmed in September, and treatment with sulfasalazine and prednisolone (10 mg daily) was started. Because of incomplete response, Siegfried Wassenberg, MD, Rolf Rau, MD, PhD: Evangelisches Fachkrankenhaus, Ratingen, Germany. Address correspondence and reprint requests to Siegfried Wassenberg, MD, Department of Rheumatology, Evangelisches Fachkrankenhaus, Rosenstrasse 2, D-40882 Ratingen, Germany. E-mail: firstname.lastname@example.org. Submitted for publication March 25, 2002; accepted in revised form July 10, 2002. 2804 RADIOLOGIC VIGNETTE 2805 Radiographic changes Left hand and wrist. In 1997 there was soft tissue swelling at the ulnar and radial aspects of the left wrist, the second MCP joint, and the second and third PIP joints. Erosions were present at the ulnar styloid process and the distal radius; the navicular bone was almost Figure 1. Second metacarpophalangeal joint of the left hand. 1997, The distal portion of the metacarpal head, representing ⬃70% of the head, has nearly completely disappeared, with almost no bone structure left; the cortical plate is mostly destroyed. Bone resorption and cortex destruction are also present at the base of the proximal phalanx. 1998, New bone fills the previous “osteolysis”; the margin of this new bone is sclerosed and the cortical plate is rebuilt. The joint surface is still somewhat irregular. The bone at the base of the phalanx is also sclerosed. 1999/2000, The tendency toward rebuilding a normal shape of the joint continues. gymnastics, swimming, bicycling, working in the garden, and managing her household. The ESR was 19 mm/ hour, the CRP level was normal (0.5 mg/dl), and rheumatoid factor was again negative. The patient was then followed up in the outpatient clinic every 6 months, and her RA remained in remission (last visit November 2001). Her functional capacity remained completely normal. She continued to bicycle, jog, work in the garden, and run her household without any limitations. Her hemoglobin level had increased from 11.3 gm/dl in 1997 to 13.8 gm/dl in 2001. The ESR at the last visit was 14 mm/hour. Figure 2. Fifth metatarsophalangeal joint of the left foot. 1997, The metatarsal head appears to be severely destroyed by a long erosion at the fibular aspect; the margin of this erosion is fuzzy and indistinct. The cortical plate is resorbed. Within the subchondral bone there are additional erosions shown en face, appearing as cysts. There is a large radiolucent area (“cyst”) near the tibial aspect of the bone. Subchondral osteoporosis is evident at the base of the proximal phalanx. 1998, The bone structure appears to be more dense and somewhat sclerosed, the “cysts” have been filled in, the edge of the fibular erosion has become less irregular, and there is again an impression of a cortical plate. The erosion has flattened compared with 1997. 1999, The bone sclerosis has further increased. The shape of the erosion, previously concave, has become convex, partly due to new bone formation. 2000, There is a tendency toward rebuilding of the original metatarsal head (remodeling). 2806 RADIOLOGIC VIGNETTE cysts and erosions were present at the ulnar styloid, the distal radius, and the navicular, multangular, and capitate bones. Erosions could also be seen at all metacarpal bases, the second MCP joint, and the third DIP joint, with smaller erosions also at the second and fourth DIP joints. With time, filling in of these erosions and development of bony sclerosis could be observed. Soft tissue swelling disappeared. Both forefeet. In 1997 radiographs demonstrated splay feet, with subluxation of the MTP joints and hallux valgus. There were extensive erosions at the first, third, and fifth MTP joints of the left foot, and erosions were also present, though less extensive, at all MTP joints of the right foot. During followup, impressive reparative changes with remodeling became obvious. Sequential radiographs obtained between 1997 and 2000 are shown in Figures 1–3. Discussion Figure 3. Third metatarsophalangeal joint of the left foot. 1997, There are several large and deep erosions with indistinct margins on both sides of the metatarsal head and at the base of the proximal phalanx. At these sites, the bone is almost completely resorbed. The cortical plate has disappeared, and nearly no articulating joint surface is preserved. 1998, At the sites of previous “osteolysis” at the metatarsal head, bone structure has reappeared. New bone fills in the previous defects. The bone is sclerosed. The erosion at the base of the proximal phalanx has also been filled in. 1999/2000, New bone formation has continued, and the cortical plate appears normal again. There is a tendency toward formation of a normal metatarsal head and a normal base of the phalanx, including restoration of joint space. In 2001 (not shown), the tendency toward normalization continued. completely destroyed. There were also erosions at the multangular and capitate bones and the second MCP, third PIP, and third DIP joints. During followup, soft tissue swelling disappeared, and the erosions were filled in by newly formed bone; the subchondral bone showed signs of sclerosis. Right hand and wrist. Radiographs obtained in 1997 revealed soft tissue swelling at the right wrist, the second MCP joint, and the third DIP joint. Subchondral The present case demonstrates that clinical remission could be achieved within 1 year of monotherapy with MTX in a patient with active and severely erosive RA and that after 1 year, clear reparative changes with filling in of erosions and bone sclerosis could be observed radiographically. Clinical remission has been sustained for 4 years, with complete restoration of functional capacity and further stabilization of the previously severely destroyed joints. Several forms of repair were observed: 1) recortication, 2) partial or complete filling in of erosions, and 3) remodeling with a tendency to regain shape for normal function. In some cases, secondary “osteoarthritis” may develop in other joints, characterized by joint space narrowing, subchondral sclerosis, and osteophyte formation. Previous reports have also described healing of eroded joints in RA (1–11). With conventional DMARDs (sometimes called “slow-acting” drugs), it takes time to achieve clinical remission, and the process of bone repair does not start until after clinical remission has occurred. There is a gap of 6–12 months between the time clinical improvement occurs and the time signs of repair can be recognized on plain radiographs (12). Complete clinical remissions are rarely seen during clinical trials and followup is usually too short to detect radiographic repair; therefore, investigators have not deemed it necessary to consider radiographic healing in the context of assessing improvement in clinical trials. With the availability of more rapidly acting and more effective drugs (i.e., tumor necrosis factor inhibitors), the need to describe repair, even RADIOLOGIC VIGNETTE within the relatively short period of clinical trials, may become crucial. Healing phenomena (or repair) can serve as direct evidence of arrested destruction in an individual joint. The scientific community should try to agree on whether and how healing phenomena can be integrated into existing scoring methods, for example, by reducing the radiographic score in the case of recortication and/or filling in. Alternatively, joints with different radiographic indicators of repair, for example recortication, filling in, “secondary” osteoarthritis, or a combination of these, could be considered in addition to conventional scoring. Moreover, the number of joints with remodeling, having regained apparently normal shape for regular function, could be noted. A standard method to quantify healing or repair of joint destruction would certainly be of benefit. 2807 4. 5. 6. 7. 8. 9. 10. 11. REFERENCES 1. Dihlman W. Über die Arthritis reformans (Thoughts about arthritis reformans). Fortschr Röntgenstr 1969;111:245–51. 2. Jalava S, Reunanen K. Healing of erosions in rheumatoid arthritis. Scand J Rheumatol 1982;11:97–100. 3. Rau R, Herborn G, Karger T, Werdier D. 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