Inaugural Cervical Vertebral Sarcoidosis
To the Editor:
Sarcoidosis is a multisystem disease of unknown origin, occurring especially in young adults. While involvement of virtually every tissue and organ has been described, the usual sites are lymph nodes, liver, spleen, lungs, skin, and the uveo parotid region. Diagnosis is supported by clinical and radiological manifestations and histological features consisting of widespread, noncaseated epithelioid cell granuloma. The precise incidence of bone marrow involvement is not known, but bone lesions are identified in 1% to 13% of patients during the course of the disease1,2. Bone lesions often involve small bones of the hands and feet. Vertebral lesions are seldom reported, located mainly at the dorsolumbar level. We describe 2 cases of cervical bone lesion revealing the features of the disease.
Case 1. From the beginning of 1992, a 38-year-old Black woman had had mechanical lumbar pain with weight loss, anorexia, and asthenia. Laboratory data showed only inflammation [erythrocyte sedimentation rate (ESR) 76 mm/h]. Radiographs showed dense and heterogeneous lesions involving the skull and cervical spine. Magnetic resonance imaging (MRI) showed abnormal signal of C1, C2, C4, C5, and C6 vertebral bodies (Figure 1).
Since tuberculosis, neoplasia, or lymphoma could readily be suggested, surgical biopsy of C4 and C5 vertebral bodies was performed for diagnosis. Histological studies rendered a conclusion of nonspecific intensive osteofibrosis. The patient was then admitted to our department in May 1993 because of persistence of symptoms and occurrence of pulsatile headache, neck pain, wrist arthralgias, and pelvic pain. Physical examination was unremarkable; there was neither lymph node enlargement nor hepatosplenomegaly.
Laboratory data showed persistent elevated ESR (70 mm/h), microcytic anemia, and hypergammaglobulinemia. The serum and urine calcium and phosphorus concentrations and the angiotensin-converting enzyme (ACE) were normal. Chest radiograph was normal. Pelvic radiograph showed mild, bilateral osteosclerotic lesions of the iliac edge of the sacroiliac joint. Skull and cervical lesions consisted of dense and heterogeneous areas confirmed by computed tomography scan (Figure 2). The rest of the skeleton was normal. A technetium 99m bisphosphonate bone scan showed disseminated uptake in the skull, the cervical spine, the fifth lumbar vertebral body, and the iliac bone.
Bone marrow aspiration was normal. Bilateral posterior iliac crest biopsies disclosed follicular lesions without necrosis or giant cells, consistent with the diagnosis of sarcoidosis.
She was then treated with prednisone at starting dosage of 1 mg/kg/day with decreasing regimen over several weeks. All aching resolved within 3 months. A 1-year followup displayed radiologic regression of the skull location of the disease. Steroid treatment was stopped.
Case 2. A 42-year-old Caucasian man was admitted in June 1993 because of cervical pain with bilateral irradiation to shoulders and arms, and finger dysesthesiae. There was no fever or weight loss. The physical examination was unremarkable. Cervical spine radiograph showed lesions of the C6 vertebral body with a lattice-like pattern (Figure 3). Chest radiograph was normal. Electromyographic investigation showed bilateral C6 radicular nerve lesions. MRI revealed a hyposignal with a T1-weighted sequence of the C6 vertebral body sparing both adjacent disks (Figure 4). Surgical biopsy of C6 was performed for diagnosis.
Histological study showed epithelioid and giant cellular follicular lesions, without necrosis. These lesions were consistent with diagnosis of tuberculosis or sarcoidosis. He was discharged home without treatment since pain was relieved spontaneously and investigations remained negative.
In June 1994, he was readmitted due to relapsing pain. There was no change in physical examination. ESR, hemoglobin, white blood cell count, and serum and urine calcium and phosphorus levels were normal. Different cultures revealed no Mycobacterium tuberculosis. ACE level was increased to 50.7 nmol/ml/min (normal 15–25 nmol/ml/min).
Chest radiograph at this time showed bilateral interstitial infiltration mainly involving the upper fields. Pulmonary function investigations were normal. Alveolar lavage disclosed CD4 lymphocyte alveolitis. Bone involvement then was retrospectively referred to diagnosis when typical lung sarcoidosis was discovered. He was treated with an initial prednisone regimen of 60 mg/day and was doing well after 9 months of followup. Steroid treatment was then stopped.
Fewer than 50 cases of vertebral sarcoidosis have been reported3-11. Involvement of the axial skeleton is rare, but is often symptomatic9. The thoracolumbar location appears as the most frequent site. Cervical involvement was found in 9 other cases (Table 1)12-20, 7 men and 2 women, with ages ranging from 14 to 59 years. The related clinical symptoms were pain in 7 cases, and possibility of neurological complications in 5 cases (4 tetraparesia and one cervicobrachial neuralgia, like our second case). In 7 cases, cervical involvement was part of a multifocal bone disease (skull, lumbar spine, ribs), like our first case.
Radiologically, the vertebral lesion appeared lytic in most of the cases. In several cases12,17,20, like ours, plain radiography showed sclerotic lesions of cervical vertebrae, and scattered lytic and sclerotic areas in one case15. This pattern is unusual, but has also been described in the lumbar vertebra6,19 and pelvic bones11.
Technetium 99m bone scintigraphy shows increased uptake in affected bones, and may reveal asymptomatic lesions, but it is nonspecific. MRI reveals a usually hypointense signal on T1-weighted sequences, and variable intensity of signal on T2-weighted sequences, mostly hyperintense in the example of lytic sarcoid lesions, and iso- or hypointense in osteoblastic reactions20. The intensity of the signal is enhanced with contrast medium21. MRI is very sensitive to detect bone infiltration revealing lesions with normal radiographs, but is not specific in sarcoidosis.
A diagnosis may be facilitated in case of typical chest radiograph findings such as hilar lymphadenopathy14,16; but this may appear later in the disease development, as in our second case.
In some cases, cervical bone involvement has occurred in patients with established or previous diagnosis of sarcoidosis15,17-20. In other circumstances14,16, this vertebral location is inaugural, as in our 2 cases, or may represent an isolated bone involvement, as in our case 2. Nevertheless, due to absence of specificity of MRI, as discussed, and the possibility of many differential diagnoses (including bone metastases, lymphomas, mastocytosis, condensing myeloma, SAPHO syndrome) and infections in cases of disc space narrowing and soft tissue involvement in lytic or sclerotic lesions, histological confirmation by biopsy or during surgery15 is recommended in these cases. Vertebral biopsy appears to be the most pertinent procedure (our second case and Jelinek, et al20), but may fail to reveal a specific lesion as in our first case. Also notable is the possibility of finding those characteristic features in iliac crest biopsies.
Treatment is based upon steroid use alone, with good clinical results as in our 2 cases14,16,18-20, or in combination with surgery15,17 in cases of severe neurological complication (tetraparesia). This emphasizes the need of an established diagnosis. In some cases with lumbar involvement, colchicine6 or methotrexate10 have been used successfully.
The response to treatment is difficult to assess, due to the paucity of cases. Surgical treatment is required in the presence of progressive neurologic deterioration and spinal instability9.
There is scant information about radiological development of the sclerotic changes of vertebral sarcoidosis. However, cases described by Young and Laman12 not treated with steroids demonstrated no changes at 1-year followup. This was also the result in our 2 observations for the cervical vertebral location, whereas we observed radiographic reduction of the sclerotic changes of the skull under steroid treatment in our case 1. However, in the case described by Perlman, et al15, after 1 year without steroids, radiological followup disclosed disease progression, with anterior erosion of the body of C5 and dense anterior bridging paravertebral ossification of C3-C4 at the time of neurological complications.
We conclude that spinal sarcoidosis is rare, especially affecting the cervical spine. This bone lesion may lead to neurological complications revealing the disease. Due to the numerous possibilities in differential diagnosis, particularly in a case with sclerotic changes, histologic proof is required to make the diagnosis. Management with steroids may be effective when there are neurologic symptoms. However, with bone destruction leading to instability, or progressive neurologic symptoms, surgical intervention is required.
DANIEL WENDLING, MD, PhD, Head, Department of Rheumatology; HÉLÈNE DESMURS, MD, Department of Rheumatology, Department of Internal Medicine; FRANÇOISE ROYER, MD, Department of Rheumatology; HELDER GIL, MD; JEAN-LOUIS DUPOND, MD, Department of Internal Medicine, University Teaching Hospital, Franche-Comté University, Besançon, France. Address reprint requests to Prof. D. Wendling, Department of Rheumatology, CHU J. Minjoz, Bld. Fleming, F-25030 Besançon, France. E-mail: firstname.lastname@example.org
2. Resnick D, Niwayama G. Sarcoidosis. In: Resnick D, Niwayama G, editors. Diagnosis of bone and joint disorders. 2nd ed. Philadelphia: W.B. Saunders; 1988:4011-32.
3. Baldwin DW, Robert JC, Croft HE. Vertebral sarcoidosis. A case report. J Bone Joint Surg Am 1974;56:629-32.
4. Brodey PA, Pripstein S, Strange G, Kohout ND. Vertebral sarcoidosis. A case report and review of the literature. AJR Am J Roentgenol 1976;126:900-2.
7. Golzarian J, Matos C, Golstein M, Stallenberg B, Depierreux M, Struyven J. Case report: Osteosclerotic sarcoidosis of spine and pelvis: plain film and magnetic resonance imaging findings. Br J Radiol 1994;67:401-4. [MEDLINE]
11. Franco M, Passeroni C, Tieulie N, Verdier JF, Benisuy D. Longterm radiographic follow-up in a patient with osteosclerotic sarcoidosis of the spine and pelvis. Rev Rhum Engl Ed 1998;65:586-90. [MEDLINE]
12. Young DA, Laman ML. Radiodense skeletal lesions in Boeck's sarcoid. AJR Am J Roentgenol 1972;114:553-8.
13. Zimmerman R, Leeds NE. Calvarial and vertebral sarcoidosis. Radiology 1976;119:384.
14. Stump D, Spock A, Grossman H. Vertebral sarcoidosis in adolescents. Radiology 1976;121:153-5.
15. Perlman SG, Damergis J, Witorsch P, Cooney FD, Gunther SF, Barth WF. Vertebral sarcoidosis with paravertebral ossification. Arthritis Rheum 1978;21:271-6.
16. Cutler SS, Sankaranarayanan G. Vertebral sarcoidosis. JAMA 1978;240:557-8.
17. Engle EA, Cooney FD. Tetraplegia secondary to cervical sarcoidosis. J Neurosurg 1979;50:665-7.
19. Bushara KO, Petermann G, Waclawik AJ, Brown WD, Schutta HS. Sarcoidosis of the spinal cord with extensive vertebral involvement: a case report. Comput Med Imaging Graphics 1995;19:443-6. [MEDLINE]