Chronic inflammatory bowel disease (IBD) is frequently associated with arthritis, especially sacroiliitis or spondylitis (1). A very rare extraintestinal manifestation of IBD is hypertrophic osteoarthropathy (HOA) (2). The full clinical syndrome of HOA is characterized by digital clubbing, painful swelling of the limbs, arthralgia, and joint effusions. Usually, a new periosteal bone formation—bilateral and symmetric along the metadiaphysis—can be seen. Hypertrophic osteoarthropathy associated with IBD has been reported in only a few cases and observed mainly in adults (2–4). In these patients, HOA occurred after diagnosis and before beginning treatment for IBD.
This article describes a 13-year-old boy with untreated ulcerative colitis (UC) and associated HOA.
A 13-year-old boy sought treatment for intermittent bloody diarrhea, fever, paleness, and acute sharp pain in his left thigh. Physical examination showed the patient was underweight (weight was 37 kg, less than the 3rd percentile and length was 155 cm, 50th percentile). No swelling, warmth, or reddening of the soft tissue was noted. Passive motion of the limbs was normal, and active motion was painful. No digital clubbing was seen. The abdomen was distended, and active bowel sounds were audible.
Past medical history revealed that diarrhea, abdominal pain, and fresh blood in the stool had been present intermittently (every 2 to 4 months) during the past 2 years.
Blood tests showed mild anemia, thrombocytosis, a shift to the left in the white blood cell count, and an increased sedimentation rate (Table 1). All cultures from blood and urine were sterile, and no pathogens were found in the stool.
In addition to the left femoral pain, an ipsilateral effusion of the knee joint and identical contralateral pain developed.
Conventional radiography of both thighs showed thickened periosteum of the femora with a thin, subperiosteal apposition of bone. Consequently, HOA was suspected (Fig. 1).
Magnetic resonance imaging (MRI) scan showed laminated thickening of the periosteum in both femora with perifocal edema of the bone marrow. Because osteomyelitis could not be excluded, antibiotic treatment was started. Bone marrow aspirate, biopsy specimen, and MRI image showed no evidence of a tumour. Skeletal scintigraphy (99Tc) showed unspecific accumulation of the marker in the diaphysis and the metaphysis of both femora (Fig. 2).
Because of intermittent bloody diarrhea during the past 2 years, colonoscopy was performed and showed pancolitis. Histologic workup confirmed the diagnosis of UC. Treatment with mesalazine was initiated. Testing for perinuclear antineutrophil cytoplasmic antibodies (pANCA) was negative.
Because there was no clinical improvement with antibiotic therapy, the original concept of HOA due to UC was reconsidered. Steroid therapy (1.8 mg/kg prednisolone daily) was initiated, resulting in rapid general improvement in clinical and laboratory findings (Table 1). Analgetic treatment was discontinued after a few days, and the boy became completely physically active again. Stool frequency decreased to one to two stools daily, and no further blood was detectable.
After a month of treatment, the steroid dosage was decreased slowly. At 0.3 mg/kg prednisolone daily, pain in the left leg and knee started again, but no abdominal symptoms developed. Steroids were increased again to 0.8 mg/kg daily for a short period and decreased slowly during the next months. A new radiologic workup showed a decrease in the subperiosteal bone formation (Fig. 3). Further decreasing the prednisolone dosage resulted in another relapse, accompanied by colitic symptoms including bloody diarrhea.
The boy has been symptom free for 14 months with a daily regimen of 0.2 mg/kg of prednisolone. During the 2 years since diagnosis and since beginning treatment, he has grown 12 cm (50th percentile of growth velocity).
In this patient, the presence of longitudinal bilateral calcifications seen in plain radiographs and the absence of intrafemoral destruction plus inconspicuous bone marrow aspirate and biopsy tissue led to the exclusion of primary and secondary neoplasm. Furthermore, there were no signs of traumatic changes or osteomyelitis. However, the edema of the bone marrow detected with magnetic resonance imaging was rather confusing and at first led to the suspicion of osteomyelitis. The alterations seen in the plain radiograph were typical of HOA.
Hypertrophic osteoarthropathy is a very rare cause of acute pain in a limb. Usually it occurs in patients with pulmonary inflammatory disease (cystic fibrosis, bronchiectasia, obstructive bronchitis), but it also has been described in patients with malignancies, heart disease, and rarely in patients with IBD and celiac disease (5,7–10,12).
Arthritis, especially sacroiliitis, is a well-known extraintestinal manifestation of IBD (11). In contrast, only 10 patients with IBD and associated HOA have been described in the literature (6 with Crohn disease, 4 with UC). In the published cases, the onset of HOA usually occurs years (4–32 years) after diagnosis of and beginning treatment for IBD. In our patient, relatively mild clinical symptoms of UC did not lead to proper investigations. Ulcerative colitis remained untreated for about 2 years and resulted in HOA.
Periostitis produced symptoms in only half of the reviewed patients. Associated arthritis was usually painful. Intensified treatment of the underlying disease rarely ameliorated the complaints (2,4,6,13–17). In most cases, distal long bones were affected as well as metatarsals and, less frequently, metacarpals. Clubbing of the fingers or toes was present in six patients.
In our patient, UC had started approximately 2 years before HOA developed and both disease entities were diagnosed simultaneously. The new bone formation at the metaphysis of the femur was not as pronounced as in the reviewed cases. The treatment with high-dose steroids led to an improvement of intestinal and bone symptoms and to decreased periosteal appositions. We conclude that the short duration of the bone disease and immediately initiated treatment of the underlying intestinal disease may prevent further progression of HOA and may improve the prognosis.
Hypertrophic osteoarthropathy is a rare extraintestinal manifestation of IBD. In our opinion, the gold standard for diagnosing HOA remains plain bone radiography. When all other differential diagnoses have been excluded, HOA should be considered and intensified treatment of IBD should be started. Early onset of consequent treatment may prevent further progression and may result in a better prognosis.
1. Meyer W. Neoplasms of bone. In: Behrman ER, ed. Nelson Textbook of Pediatrics.
15th ed. New York: WB Saunders; 1996:724–8,1080–4,1467–8.
2. Farman J, Twersky J, Fierst S. Ulcerative colitis associated with hypertrophic osteoarthropathy. Am J Dig Dis 1976; 21:130–5.
3. Bywaters EGL, Ansel BM. Arthritis associated with ulcerative colitis, a clinical and pathologic study. Ann Rheum Dis 1958; 17:169–72.
4. Homska WL, Streng H, Hammarsten J. Hypertrophic osteoarthropathy and chronic ulcerative colitis. Gastroenterology 1967; 33:489–92.
5. Arlat IP, Maier W, Leupold D. Massive periosteal new bone formation in ulcerative colitis. Radiology 1982; 144:507–8.
6. Oppenheimer DA, Jones HH. Hypertrophic osteoarthropathy of chronic inflammatory bowel disease. Skeletal Radiol 1982; 9:109–13.
7. Gilliland BC. Disorders of the immune system, connective tissue, and joints. In: Isselbacher KJ, Braunwald E, Wilson JD, et al, eds. Harrison's Principles of Internal Medicine. New York: McGraw-Hill; 1991:1486–7.
8. Resnick D. In: Resnick D, ed. Bone and Joint Imaging.
San Diego: WB Saunders; 1996:280–2.
9. Kempe CH. The battered child syndrome. J Am Med Ass 1962; 181:17–21.
10. Bloom RA, Assaf Y, Verstanding A. Hypertrophic osteoarthropathy and primary intestinal lymphoma. Gastrointest Radiol 1986; 11:185–6.
11. Sons HU, Dannberg A, Jerosch J. Orthopädische Aspekte bei Morbus Crohn. Beitr Orthop Traumatol 1990; 37:539–44.
12. Schumacher HR. Articular manifestations of hypertrophic pulmonary osteoarthropathy in bronchogenic carcinoma. A clinical and pathologic study. Arthritis Rheum 1976; 19:629–36.
13. Brom B, Bank S, Marks IN. Periostitis, aseptic necrosis and arthritis occurring in a patient with Crohn's disease. Gastroenterology 1971; 60:1106–10.
14. Neal G, Kelsall AR, Doyle FH. Crohn's disease and diffuse symmetrical periostitis. Gut 1968; 9:383–9.
15. Pastershank SP, Tchang SPK. Regional enteritis and hypertrophic osteoarthropathy. J Can Assoc Radiol 1972; 23:35–9.
16. Streuli R, Pouliadis G. Periostale Knochenneubildung bei Morbus Crohn. Schweiz Med Wochenschr 1978; 108:518–21.
17. Arlart IP, Maier W, Leupold. Massive periosteal new bone formation in ulcerative colitis. Radiology 1982; 144:507–8.