Although peripheral arthritis is the most common extra- intestinal manifestation of inflammatory bowel disease, it is very rarely addressed in the orthopaedic literature. The overwhelming majority of patients with inflammatory bowel disease present with gastrointestinal symptoms and do not have any joint involvement until much later. We present the case of a patient who had joint pain and swelling but lacked any sign of gastrointestinal involvement. After five months of work-up, the patient was diagnosed with Crohn disease and the joint symptoms improved with appropriate medical treatment. We believe that inflammatory bowel disease should be considered in the differential diagnosis of joint pain and swelling. Our patient was informed that data concerning the case would be submitted for publication.
Case Report
A twenty-two-year-old male active-duty sailor in the United States Navy presented with a six-week history of right knee pain following a twisting injury that he had sustained while climbing a ladder on a ship; the knee twisted as the trunk rotated on the planted ipsilateral foot. At the time of the initial orthopaedic evaluation, the patient reported that pain and swelling in the right knee had failed to respond to a course of anti-inflammatory medication and activity modification. There was no history of clicking, catching, locking, or snapping. A review of systems was negative for fevers, chills, nausea, vomiting, recent sexual contact, recent weight loss, loose stools, abdominal pain, or a history of other joint pain or swelling.
Physical examination of the knee revealed a moderate effusion, normal appearance of the skin, mild warmth to touch, and decreased range of motion from 0 to 100 secondary to pain and swelling. There was diffuse tenderness of the anterior fat pad but no tenderness at the joint line. Provocative testing of the knee in varus and valgus, the Lachman test, the McMurray test, and the drawer tests all revealed negative results. Strength and sensation in the lower extremity were normal. At this point, the patient was treated nonoperatively with anti-inflammatory medications, activity modification, and a directed course of physical therapy.
At the four-week follow-up visit, the patient still had pain, swelling, and persistent effusion of the right knee. Aspiration of the right knee yielded 10 mL of bloody fluid that revealed an inflammatory effusion with a large amount of red blood cells (165,000), and some white blood cells (22,000). A gram stain revealed polymorphonuclear leukocytes without organisms, and an analysis of the synovial fluid showed no crystals. Because of the persistence of pain, warmth, and effusion but lack of mechanical symptoms, the differential diagnosis included pigmented villonodular synovitis, traumatic knee injury (meniscal tear or ligament injury), and advanced patellofemoral pain syndrome.
A magnetic resonance imaging scan demonstrated intact cruciate and collateral ligaments and normal menisci. A moderate joint effusion was evident along with thickening of the synovium that was consistent with synovial hyperplasia, but no pigmented villonodular synovitis was seen (Figs. 1-A and 1-B). The patient underwent arthroscopy of the knee for the performance of partial synovectomy. On arthroscopic examination, the synovium was found to be markedly hypertrophic, especially in the anterior and medial and lateral gutters of the knee (Figs. 2-A and 2-B). Histologic examination of the synovitic material demonstrated acute and chronic inflammation, granulation tissue, histiocytes, subsynovial multinucleated giant cells, fibrin deposition, and microscopic hemosiderin deposition. However, despite the hemosiderin deposition, there was no nodular or villonodular proliferation consistent with pigmented villonodular synovitis (Fig. 3). Laboratory data obtained at this time demonstrated a microcytic anemia (hemoglobin level of 12.1 g/dL [121 g/L], hematocrit of 36.3% [0.363], mean corpuscular volume of 71 fL, an erythrocyte sedimentation rate of 51 mm/hr, and a C-reactive protein level of 15.7 mg/dL [0.16 mg/L]). Due to the inflammatory nature of the findings, additional laboratory data were obtained, including phenotyping for HLA B-27 (human leukocyte antigen B-27) and testing for antinuclear antibody (ANA) titers and rheumatoid factor, all of which revealed negative results. Additional physical therapy was prescribed, and a rheumatologic consult was obtained.
Figs. 1-A and 1-B T1-weighted (Fig. 1-A) and T2-weighted (Fig. 1- B) sagittal magnetic resonance images of the right knee, demonstrating moderate effusion and synovitis. There is a large collection of fluid in the knee; however, there are no characteristic findings of pigmented villonodular synovitis.
Approximately six weeks after surgery, the patient presented with similar symptoms in the contralateral knee. The rheumatologic work- up demonstrated a similar inflammatory knee effusion and a worsening microcytic anemia (the results of iron studies were consistent with iron deficiency), and an anteroposterior radiograph of the pelvis demonstrated sclerosis and early erosive changes of the sacroiliac joints without ankylosis. An upper gastrointestinal series with small-bowel follow-through was ordered. (With this test, the patient drinks barium and then radiographs are made as the contrast medium empties out of the small intestine and into the large intestine. Although the test is not specifically used to study the colon, pathological processes can be visualized as the contrast medium travels through the colon.) The small-bowel follow-through revealed a cobblestone mucosal pattern of the entire colon with absence of the haustral pattern and likely backwash ileitis with narrowing of the ileocecal valve. A colonoscopy demonstrated focal chronic and active colitis with microabscesses and granulomatous inflammation with necrosis throughout the colon. The ulcerations, the focal nature of the changes, the granulomatous inflammation, and the extension of the inflammation below the mucosa were consistent with a diagnosis of Crohn disease, a chronic inflammatory gastrointestinal disease of unknown etiology.
Figs. 2-A and 2-B Arthroscopic view from the lateral portal, demonstrating marked synovitis in the medial (Fig. 2-A) and lateral gutters as well as in the suprapatellar pouch (Fig. 2-B).
Fig. 3
Photomicrograph of the synovial biopsy specimen, demonstrating acute and chronic inflammatory cells, granulation tissue, multinucleated giant cells, and microscopic hemosiderin deposition without nodular or villonodular proliferation (hematoxylin and eosin, 10).
Soon thereafter, the patient began to have multiple loose stools, with cramping, each day, arthralgia in the left hip and right wrist, episcleritis in the right eye, and approximately ten deep, pus- filled ulcers on the anterior aspect of the leg. The ulcers each were approximately 1 cm in diameter and were confirmed by biopsy to be pyoderma gangrenosum. These new clinical findings, together with the findings of inflammatory arthritis of the knee and sacroiliitis, further supported the diagnosis of Crohn disease. The patient was treated with sulfasalazine, high-dose prednisone, azathioprine, and iron. The knee pain and swelling, diarrhea, episcleritis, synovitis, anemia, and pyoderma gangrenosum all resolved, and the patient was able to taper off the oral corticosteroid medication over a two- month period. He returned to full military duties, without recurrent effusion or pain in either knee.
Discussion
Acute knee injuries are common in young adults. We describe the case of a young man with no pre-injury joint symptoms who presented with a low-energy injury to the knee along with diffuse swelling, effusion, and loss of motion that persisted despite rest, physical therapy, and anti-inflammatory medications. A magnetic resonance imaging scan was ordered to help narrow the differential diagnoses to either trauma or synovitis. Although there were no gastrointestinal symptoms, the patient’s rheumatologist suspected that the diagnosis was inflammatory bowel disease on the basis of the findings of anemia, oligoarthritis, and asymptomatic sacroiliitis; however, it was not until the colonoscopy was performed that Crohn disease was confirmed.
Musculoskeletal manifestations of inflammatory bowel disease include peripheral arthritis, granulomatous monarthritis, sacroiliitis, and ankylosing spondylitis1, with peripheral arthritis being the most common manifestation2. The knees are the most commonly affected joints2,3, followed by the ankles, elbows, wrists, and shoulders1. The symptoms include pain, swelling, tenderness, and a decreased range of motion1,2. As the inflammation in one joint abates, another joint often becomes affected. The arthritis usually resolves within one to three months after the onset of symptoms and is self-limited, with approximately 90% of the episodes lasting four weeks or less4. Joint erosion is rare. In one series, 71% of thirty- four cases of peripheral arthritis that occurred with Crohn disease were oligoarticular4. Extra-articular manifestations are rare in patients with Crohn disease. In one study3 of patients with Crohn disease, the rate of pyoderma gangrenosum was 1.1% (five of 449) and the rate of iritis or uveitis was 6.4%(twenty-nine of 449) but there were no cases of hemolytic anemia. However, when cutaneous or ocular symptoms are seen in addition to articular manifestations, abdominal disease should be suspected.
The link between inflammatory bowel disease and peripheral arthritis has been established. Several studies have described the prevalence of peripheral arthritis in patients with Crohn disease to be 11% (seventeen of 160) to 16% (eighty-four of 521)5,6. Crohn disease does not seem to affect one gender more than the other; one study4 showed that 13% (eight) of sixty-three men and 14% (fifteen) of 104 women had peripheral arthritis.
Peripheral arthritis usually is manifested only after the inflammatory bowel disease has been diagnosed for some time6. The case of our patient reflects the rare presentation of peripheral arthritis prior to the onset of gastrointestinal symptoms. The severity of the arthritis usually mimics the activity of the bowel disease, and the arthritis usually abates with medical treatment3, underscoring a direct relationship between intestinal exacerbations and joint symptoms2,3. Extraintestinal manifestations are most frequently encountered with ileocolitis (28% to 61% of cases), then colitis (range, 26% to 47% of cases), and then ileitis (13% to 19% of cases)2,3,6. Surgery of the affected joint probably does not influence the natural history of peripheral arthritis; rather, medical management is the mainstay of therapy because the disease is due to a systemic process.
Various theories have been proposed with regard to the method in which inflammatory bowel disease causes peripheral arthritis. One such theory suggests that the gastrointestinal tract acts as a protective barrier between the gut and the serum until inflammation in the bowel causes an increase in gut permeability, which leads to transfer of bacterial antigens from the gut to the serum. Additionally, there may be cross-reactivity between antigens in the intestine, synovium, skin, eyes, and biliary tree7. Furthermore, the bacterial products lead to activation of immunoregulatory cells, complement, and proinflammatory cytokines7,8. The synovial fluid and tissue show nonspecific inflammatory changes2; however, several case reports have demonstrated noncaseating granulomas of the synovium9- 11.
The primary care provider is usually the first to diagnose an inflammatory bowel condition and is therefore more likely to be alert to the extra-articular manifestations of these conditions3. However, on occasion, the orthopaedic surgeon may be the first physician to evaluate a patient with persistent joint pain and swelling and thus should be aware of the extraarticular systemic causes of joint pain and swelling.
References
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2. Resnick D. Enteropathic arthropathies. In: Resnick D, Niwayama G, editors. Diagnosis of bone and joint disorders. 2nd ed. Philadelphia: Saunders; 1988. p 1219-30.
3. Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996;23:29-34.
4. Munch H, Purrmann J, Reis HE, Bertrams J, Zeidler H, Stolze T, Miller B, Korsten S, Cremers J, Strohmeyer G. Clinical features of inflammatory joint and spine manifestations in Crohn’s disease. Hepatogastroenterology. 1986; 33:123-7.
5. Salvarani C, Vlachonikolis IG, van der Heijde DM, Fornaciari G, Macchioni P, Beltrami M, Olivieri I, Di Gennaro F, Politi P, Stockbrugger RW, Russel MG; European Collaborative IBD Study Group. Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients. Scand J Gastroenterol. 2001;36:1307-13.
6. Palm O, Moum B, Jahnsen J, Gran JT. The prevalence and incidence of peripheral arthritis in patients with inflammatory bowel disease, a prospective population-based study (the IBSEN study). Rheumatology (Oxford). 2001;40:1256-61.
7. Levine JB, Lukawski-Trubish D. Extraintestinal considerations in inflammatory bowel disease. Gastroenterol Clin North Am. 1995;24:633-46.
8. Wollheim FA. Enteropathic arthritis: how do the joints talk with the gut? Curr Opin Rheumatol. 2001;13:305-9.
9. Al-Hadidi S, Khatib G, Chhatwal P, Khatib R. Granulomatous arthritis in Crohn’s disease. Arthritis Rheum. 1984;27:1061-2.
10. Toubert A, Dougados M, Amor B. Erosive granulomatous arthritis in Crohn’s disease. Arthritis Rheum. 1985;28:958-9.
11. Hermans PJ, Fievez ML, Descamps CL, Aupaix MA. Granulomatous synovitis and Crohn’s disease. J Rheumatol. 1984;11:710-2.
BY LIEUTENANT MARIUSZ A. OLSZEWSKI, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE, COMMANDER RICHARD E. MANOS, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE, COMMANDER PETER J. WEIS, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE, AND LIEUTENANT COMMANDER MATTHEW T. PROVENCHER, MD, MEDICAL CORPS, UNITED STATES NAVAL RESERVE
Investigation performed at the Departments of Orthopaedic Surgery and Rheumatology, Naval Medical Center San Diego, San Diego, California
Lieutenant Mariusz A. Olszewski, MD, Medical Corps, United States Naval Reserve
Commander Richard E. Manos, MD, Medical Corps, United States Naval Reserve
Commander Peter J. Weis, MD, Medical Corps, United States Naval Reserve
Lieutenant Commander Matthew T. Provencher, MD, Medical Corps, United States Naval Reserve
Departments of Orthopaedic Surgery (M.A.O., R.E.M., and M.T.P.) and Rheumatology (P.J.W.), Naval Medical Center San Diego, 34800 Bob Wilson Drive, Suite 112, San Diego, CA 92134-1112
The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States government.
doi:10.2106/JBJS.D.01822
Copyright Journal of Bone and Joint Surgery, Inc. Aug 2005
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