A 40-year-old woman was diagnosed with Crohn’s disease in December 2000. The patient was started on steroids among other medications with a poor response. Steroids were discontinued after 8 months of use. Six months after stopping steroids the patient developed bilateral shin pains. A diagnosis of ischemic necrosis of the bilateral tibia and fibula was made on magnetic resonance imaging and confirmed on bone biopsy of the right tibia.
This case represents the first report of ischemic necrosis of the shins in Crohn's disease and emphasizes the possible unusual site of presentation of this entity, the diagnostic modalities, and the limited therapeutic options. A review of ischemic necrosis of the bone with special reference to inflammatory bowel disease is done.
A 40-year-old white woman was diagnosed with Crohn’s disease in December 2000 and started on mesalamine, prednisone, and mesalamine enemas. The patient was maintained on a varying steroid dose of from 20 to 60 mg per day and 2 episodes of intravenous steroids when she was hospitalized for exacerbation of symptoms. Prednisone was discontinued after 8 months when the patient was stabilized on azathioprine.
Six months after discontinuing steroids the patient developed bilateral shin pains, low-grade fever up to 99.9ºF, and a mild flare of her Crohn’s disease. There was no history of trauma. Pain was gradual in onset, dull, and only partially relieved with acetaminophen and hydrocodone tablets.
The patient was admitted to the hospital for workup of the shin pain and control of diarrhea. The middle of the shins were exquisitely tender to touch bilaterally. There were no accompanying skin changes, no swelling of the joints, no limitation of movement at the ankle or the knee and the distal pulses were normal bilaterally.
X-rays of both legs were normal. No abnormalities were detected on the arterial and venous Doppler studies of the bilateral lower extremities.
MRI of the legs without intravenous contrast revealed patchy areas of increased STIR and T2 signal within the marrow space of both tibia and fibula. This was most severe on the right side with the largest lesion measuring approximately 3 cm in length in the mid-diaphysis of the right tibia, extending across the entire marrow space (Figure 1).
Figure 1 Coronal Fast STIR MRI image through the calves shows bilateral patchy areas of increased signal along the tibial cortex and the medulla (arrow). The characteristic double rim lesion typical of avascular necrosis is not yet present at this stage. Although there is a thin rim of periosteal fluid along the tibiae, the periosteum itself remains intact. This finding argues against osteomyelitis, but at this stage does not exclude other infiltrative bone marrow processes.
The remaining lesions were smaller. These lesions also displayed slightly decreased signal on the T1 weighted signal. There was no MRI evidence of cortical destruction to suggest osteomyelitis. No fractures were visualized. No soft tissue lesion or surrounding muscle or soft tissue edema was visualized. Bone-scan revealed normal bone density and lack of other lesions.
Due to the unusual location and concern for possible osteomyelitis or other infiltrative lesions, bone marrow biopsy of the mid-portion of the right tibial diaphysis was done.
Core decompression was simultaneously achieved along with the biopsy. Non-viable bone as demonstrated by lack of nucleoli in bone lacunae and necrosis of bone marrow was seen (Figure 2).
Figure 2 Hematoxylin and eosin stain (x 200). Non-viable bone as demonstrated by lack of nucleoli in bone lacunae (L) and necrosis of bone marrow (NB). Pathological alteration of the periosteum is absent (not visualized). Cultures of the marrow had no bacterial/fungal growth.
Pathological alteration of the periosteum was absent. Multiple blood cultures along with bacterial, fungal, and mycobacterial stains and cultures of the bone were negative.
Fasting lipids, protein C, proteins S, anti-thrombin III, homocystine, and tissue plasminogen activator inhibitor were within normal limits. Factor V leiden and antiphospholipid antibodies were absent. Pain was controlled by opioids and the patient received an infusion of infliximab prior to discharge. One year after discharge she continues to be afebrile with resolution of pain and discontinuation of opioid analgesics.
Ischemic necrosis is also known as aseptic necrosis, osteonecrosis, avascular necrosis, and osteochondritis dissecans. It affects patients primarily in the third through fifth decades of life . It occurs most commonly in the femoral head but also affects the knee, shoulder, ankle, elbow, wrist, calcaneus, and rarely the tibia. Ischemic necrosis of the tibia has been described in patients with steroid use , systemic lupus erythematosus, decompression sickness, upper tibial osteotomy but not in inflammatory bowel disease.
Ischemic necrosis, as the name suggests, results from the interruption of the blood supply to the bone. This may happen due to at least 1 of the 4 mechanisms outlined in Figure 3.
Figure 3 Causes of ischemic necrosis of bone.
These factors can singly or as a combination of factors can cause osteonecrosis . If uninterrupted, this vicious amplification cycle eventuates in bone necrosis and collapse .
Ischemic necrosis has been associated with hemoglobinopathies, Gaucher’s disease, Fabry’s disease, coagulopathy, steroid use, decompression sickness, trauma, pancreatitis, systemic lupus erythematosus, rheumatoid arthritis, arterial embolus, hyperuricemia, pregnancy, familial hyperlipidemia, Cushing’s disease, tobacco and alcohol use, and inflammatory bowel disease. Approximately 30% of the patients have idiopathic ischemic necrosis .
Initial reports suggested that steroid therapy was necessary for the development of ischemic necrosis in inflammatory bowel disease. However recent evaluation of published data reveals no consistent association between ischemic necrosis and steroid treatment in IBD patients . Ischemic necrosis is a rare complication of Crohn’s disease. Overall rate of ischemic necrosis in Crohn’s disease was less than 0.5% (4 out of 877 subjects) in one study .
Clinically ischemic necrosis presents with pain and limitation of movement in half to two-thirds of the patients. It may be sudden or insidious and is usually incapacitating. In patients with inflammatory bowel disease with steroid-related ischemic necrosis, multiple joints may be involved. Body scintigraphic bone scans may be the most cost-effective means for screening for multifocal involvement, though not enough data is available to confirm if this is the best approach .
Diagnosis of ischemic necrosis can be done with radiographs, bone scan, MRI, intraosseous pressure measurement and biopsy. Radiograph is the initial step in diagnostic evaluation. Abnormalities evident on the bone scan may precede radiological changes by 2 to 18 months . Initially ischemic necrosis appears as a "cold" area surrounded by a region of increased activity, also called the "doughnut sign" . Within few weeks the site reveals uniformly increased activity or "hot" areas due to repair of the necrotic bone causing increased radionuclide uptake.
MRI shows a reduced signal with both T1 and T2 weighting . On T2 weighted images, a high-signal intensity line may be found within the single density line seen on T1 called the double-line sign . MRI also helps calculate volume of lesion as in the femoral head which may predict risk of collapse . Measurement of bone marrow pressure and venography have also been used as diagnostic modalities. Histologically, a necrotic, a granulomatous or fibrous, and a viable zone are noted in the involved bone . Empty lacunae involving multiple adjacent trabeculae are diagnostic of ischemic necrosis . Necrotic osteocytes may appear normal for weeks by light microscopy, which means that empty lacunae are a late feature of bone death.
The first stage of repair in experimental ischemic necrosis is the invasion of the necrotic marrow by capillaries and undifferentiated mesenchymal cells. The marrow is resorbed and replaced by proliferating hemopoetic tissue. When the repair process encounters cancellous bone, as it usually does, osteoblasts differentiate to form appositional new bone on the surfaces of the necrotic spicules. This phenomenon explains the increase in radiodensity of the cancellous bone during the reparative phase . Cartilagenous surface cells remain relatively intact and viable .
Management of ischemic necrosis depends upon multiple factors including site of injury. The major treatment options include medical management, core decompression, osteotomy, muscle pedicle graft, iliac bone graft, prosthetic replacement, arthroplasty.
Management of ischemic necrosis in a segment of the tibia may requires only short-term immobilization of the knee, non-steroidal anti-inflammatory drugs, exercises and limitation of weight bearing . Our patient was managed with opioids and acetaminophen for pain control for several months. Since there was no cortical involvement weight bearing continued.
Although ischemic necrosis of the bone has been most commonly described in the hip, it is important to be alert to the possibility of involvement of other sites with unexplained skeletal pain in IBD. Physicians need to maintain a high index of suspicion for ischemic necrosis of the bone and should distinguish it from the migrating and transient arthropathy of inflammatory bowel disease. Patients with involvement of sites other than the hip should be evaluated for multifocal involvement.
The cause and effect relationship between steroid use and ischemic necrosis of the bone has not been demonstrated conclusively. Well-documented cases of idiopathic ischemic necrosis of the bone should be continued to brought to attention; analyzing data from such case-reports will contribute to the further understanding of this intriguing phenomenon.
This case was first published on GastroHep.com on 19 January 2004.
Dr Aditya Gupta, MD1 Dr Joseph H. Sellin, MD, FACG2
1. Resident - Internal Medicine University of Texas Health Science Center at Houston, 6431 Fannin, MSB 1.150, Houston TX 77030, USA
2. Professor of Medicine and Integrative Biology University of Texas Health Science Center at Houston, 6431 Fannin, MSB 4.234, Houston TX 77030, USA
Dr Joseph Sellin MD FACG The University of Texas Medical Branch, 301 University Boulevard, Route 0764, Galveston, Texas 77555-0764, USA Telephone: 409-747-3075; Fax: 409-772-4789 email@example.com
- Mont MA, Hungerford DS. Non-traumatic vascular necrosis of the femoral head. J Bone Joint Surgery 1995; 77A: 459-74.
- Gold DA, Abdelwahab IF, Hermann G. Osteonecrosis of both medial tibial condyles following short-term steroid therapy. A case report. Bull Hosp Jt Dis Orthop Inst 1989; 49(1): 103-6.
- Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 1992; 326(22): 1473-79.
- Zizic TM, Holt PA. Ischemic necrosis of bone. In: Bayless TM and Hanauer SB, eds. Advanced Therapy of Inflammatory Bowel Disease. Hamilton: B. C. Decker, 2001: 293-8.
- Freeman HJ. Osteomyelitis and osteonecrosis in inflammatory bowel disease. Can J Gastroenterol 1997; 11(7): 601-6.
- Freeman HJ, Freeman KJ. Prevalence rates and an evaluation of reported risk factors for osteonecrosis (avascular necrosis) in Crohn’s disease. Can J Gastroenterol 2000; 14(2): 138-43.
- LaPorte DM, Mont MA, Mohan V, et al. Multifocal osteonecrosis. J Rheumatol 1998; 25(10): 1968-74.
- Dumont M, Danais S, Taillefer R. “Doughnut” sign in avascular necrosis of the bone. Clin Nucl Med 1983; 9: 44.
- Genez BM, Wilson MR, Houk RW, et al. Early osteonecrosis of the femoral head: detection in high-risk patients with MR imaging. Radiology 1988; 168: 521-4.
- Nishii T, Sugano N, Ohzono K, et al. Significance of lesion size and location in the prediction of collapse of osteonecrosis of the femoral head: a new three-dimensional quantification using magenetic resonace imaging. J Orthop Res 2002; 20(1): 130-6.
- Epstein NN, Tuffanelli DL, Epstein JH. Avascular bone necrosis - a complication of long-term corticosteroid therapy. Arch Dermat 1965; 92: 178-80.
- Cruess RL. Osteonecrosis of bone. Current concepts as to etiology and pathogenesis. Clin Orthop 1986; 208: 30-9.