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Correspondence

Why "Spondylodiscitis," Why "SAPHO Syndrome"?

To the Editor:

I read the recent article by Dr. Akisue and colleagues¹ concerning their experience with lumbar spondylodiscitis in SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) with great interest, and would like to offer my opinion on this case.

German rheumatologists and radiologists see this problem differently, based on longterm and extensive experiences with the SAPHO syndrome and its inflammatory effect on the spine.

We clinically, radiologically, and histopathologically surveyed 144 cases corresponding to the criteria of the SAPHO syndrome². Our cohort, moreover, documents the nosologic heterogeneity of the SAPHO syndrome, which is not a uniform entity³: 64 cases (44%) clearly belong to the "chronic recurrent multifocal osteomyelitis" (CRMO) category. Their assignment to all age classes with a peak between 15 and 20 years of age (mainly female) became possible due to the definition of this acquired, sterile inflammatory disease of the bone marrow as an "adult CRMO"⁴. In our cohort these are represented by 23 cases, 13 female, between 18 and 60 years of age.

We define the CRMO syndrome as primarily a chronic poly-osteomyelitis that also occurs monostotically and that immunopathogenetically is likely a form of "reactive osteomyelitis." Hypovirulent commensal germs like Propionibacterium acnes are considered as likely antigens. This osteomyelitis proceeds histopathologically in 3 stages as a lympho-plasma-cellular process that begins as edema of the bone marrow, which can be seen on magnetic resonance tomography, and limits itself after several years of sclerosing, or often hyperostosing. We have described the accompanying ossifying periostitis and inflammatory surrounding paraosseous resp. perivertebral soft tissue edema with possible neural and vascular complications⁵.

The manifold osteoarticular panorama can be subdivided in accord with the clinical dominance of the disease into various types, whereas the pediatric-metaphysial type affects mainly the lower extremities, with sympathetic arthritis; the pelvic type with sympathetic coxitis from acetabular inflammation; the inflammatory anterior chest wall syndrome, often with primarily chronic osteomyelitis of the clavicula; and the vertebral type (spondyloarthropathies) are the most frequent locations of the bone marrow process. The association with pustular dermatoses, that is, mainly the palmoplantar type of pustular psoriasis, increases with the manifestation age from 30% to 70% of the respective age group. In our cohort these are represented by 32 cases (50%).

In our CRMO cohort 22 cases (33%) had spinal involvement, and 8 of these cases were young women with the palmoplantar type of pustular psoriasis. The radiological and histopathological substrate is sterile lympho-plasma cellular spondylitis, which primarily occurs as an inflammatory edema of the bone marrow. Similar changes were seen in the case described by Akisue, et al in a 22-year-old woman with the affected 5th lumbar vertebra with typical signal intensity in the magnetic resonance T-T2 sequence or after the administration of a contrast medium. In our cohort of 22 patients we observed the involvement of 72 vertebral bodies from C3 to L5, 15 times multisegmentally, and 7 times deforming, and in 2 cases it was destructive up to the vertebrae plana.

Akisue, et al in their report describe the inflammation of the bone marrow (Figure 3), initially in stage I also erosive (Figures 1 and 2) in this way resembling a spondylodiscitis. In the vertebral manifestation of CRMO we believe the spondylodiscitis is always a secondary complication, the primary manifestation being chronic osteomyelitis, i.e., sterile spondylitis. This is also nosologically more understandable, because the sterile primary spondylodiscitis is an inflammatory enthesopathic symptom of the spondyloarthropathies, as seen in the psoriatic form with ossifying enthesitis. CRMO, however, in our view, is based on a primary inflammation of the bone marrow, in the case of the spine primarily a spondylitis, which may be confused with a spondyloarthropathy with secondary spondylodiscitis, making for a very difficult differential diagnosis. We have described these manifestations in the largest cohort to date⁴.

Our therapy has been successful in 28 patients with combined longterm medication using azithromycin (as immunomodulator) and (osteotrope) calcitonin^2,6.

In summary, we would classify this case as a vertebral type of the CRMO syndrome. In our view it is primarily a chronic osteomyelitis (spondylitis) of the 5th lumbar vertebrae with secondary spondylodiscitis and typical prevertebral edema.

FRITZ SCHILLING, MD, Professor of Clinical and Radiological Rheumatology, Klinikum der Johannes Gutenberg, University of Mainz, Hebbelstrasse 20, D-55127 Mainz, Germany.

REFERENCES

1. Akisue T, Yamamoto T, Marui T, et al. Lumbar spondylodiscitis in SAPHO syndrome: multimodality imaging findings. J Rheumatol 2002;5:1100-1.

2. Schilling F. SAPHO, CRMO, spondarthritides — a summary. Akt Rheumatol 2001;26:297-302.

3. Schilling F, Kessler S. The SAPHO syndrome — Clinical and radiological differentiation and classification on the basis of 86 cases. Z Rheumatol 2000;59:1-28.

4. Schilling F, Schweden F. Chronic recurrent multifocal osteomyelitis (CRMO) in adults — Presentation of the plasma cell-sclerosing process by means of four cases accompanied by pustulosis palmo-plantaris. Osteologie 1997;6:171-91.

5. Schilling F, Fedlmeier M, Eckardt A, Kessler S. Vertebral manifestation of chronic recurrent multifocal osteomyelitis (CRMO). Fortschr Röntgenstr 2002;174:1236-42.

6. Schilling F, Wagner AD. Azithromycin: The antiinflammatory and local immunomodulatory effects in chronic recurrent multifocal osteomyelitis — a preliminary communication. Z Rheumatol 2000;59:352-3.

Dr. Akisue, et al reply

To the Editor:

We read with interest Dr. Schilling's comments about our article¹. In 1987, Kahn and colleagues proposed the term SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) to designate a group of conditions that showed peculiar bone lesions with or without dermatologic lesions². It is still controversial whether the term should be used to designate these conditions, since clinical and radiographic manifestations are overlapped and combined in a condition where the etiology may not be uniform³. However, the term SAPHO syndrome has commonly been used in the English language literature, while another, acquired hyperostosis syndrome (AHYS), has also been proposed^3,4.

Dr. Schilling considers that SAPHO syndrome is not an entity with nosologic homogeneity and has proposed 5 distinct groups within SAPHO syndrome, of which chronic recurrent multifocal osteomyelitis (CRMO) is defined as type II. Based on the definition of CRMO by Dr. Schilling, our case may indeed be classified as a monostotic vertebral type of CRMO. However, CRMO was first described as a skeletal disorder with multiple bony lesions, usually affecting children and adolescents. Our case¹ was a 29-year-old woman presenting with a monostotic lesion. Therefore we do not believe that the term chronic recurrent multifocal osteomyelitis appropriately represents our case. In addition, we prefer to use the term CRMO when a patient meets the classic criteria proposed by King, et al⁷. Thus we stand by our diagnosis, based on the definitions of SAPHO syndrome by Kahn and colleagues^8,9.

The pathogenesis of SAPHO syndrome including CRMO remains unknown. Studies for vertebral lesions in SAPHO syndrome using magnetic resonance imaging (MRI) showed abnormal bone marrow signals, either focal or diffuse^10,11. Focal abnormal signals have always existed in the endplates and the corners of the vertebral bodies¹¹. In some cases, paravertebral soft tissues and intervertebral discs have also shown abnormal signal intensity, suggesting an inflammatory reactive lesion around paravertebral soft tissues and the intervertebral disc¹¹. Nachtigal, et al¹¹ concluded that MRI findings were consistent with discitis and osteitis, namely spondylodiscitis. Dr. Schilling speculates that spondylodiscitis in our patient was a secondary complication and that the primary lesion was chronic osteomyelitis in the vertebral body. However, there is no evidence that strongly indicates the initial nosologic phenomenon in our patient occurred exclusively in the bone marrow. While we appreciate the hypothesis that spondylodiscitis in SAPHO syndrome is a secondary complication and that the primary lesion could be chronic osteomyelitis in the bone marrow, we believe that radiographic and histologic evaluations confirm spondylodiscitis in our patient.

TOSHIHIRO AKISUE, MD; TETSUJI YAMAMOTO, MD; TAKASHI MARUI, MD, Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

REFERENCES

1. Akisue T, Yamamoto T, Marui T, et al. Lumbar spondylodiscitis in SAPHO syndrome: multimodality imaging findings. J Rheumatol 2002;5:1100-1.

2. Chamot AM, Benhamou CL, Kahn MF, Beraneck L, Kaplan G, Prost A. Acne-pustulosis-hyperostosis-osteitis syndrome. Results of a national survey [French]. 85 cases. Rev Rhum Mal Osteoartic 1987;54:187-96.

3. Dihlmann W, Hering L. Why the "SAPHO" syndrome? [letter]. Kahn MF [reply]. J Rheumatol 1996;23:1308-10.

4. Boutin RD, Resnick D. The SAPHO syndrome: an evolving concept for unifying several idiopathic disorders of bone and skin. AJR Am J Roentgenol 1998;170:585-91.

5. Schilling F, Kessler S. SAPHO syndrome: clinico-rheumatologic and radiologic differentiation and classification of a patient sample of 86 cases. Z Rheumatol 2000;59:1-28.

6. Bjorksten B, Gustavson KH, Eriksson B, Lindholm A, Nordstrom S. Chronic recurrent multifocal osteomyelitis and pustulosis palmoplantaris. J Pediatr 1978;93:227-31.

7. King SM, Laxer RM, Manson D, Gold R. Chronic recurrent multifocal osteomyelitis: a noninfectious inflammatory process. Pediatr Infect Dis J 1987;6:907-11.

8. Benhamou CL, Chamot AM, Kahn MF. Synovitis-acne-pustulosis hyperostosis-osteomyelitis syndrome (SAPHO). A new syndrome among the spondyloarthropathies? Clin Exp Rheumatol 1988;6:109-12.

9. Kahn MF, Khan MA. The SAPHO syndrome. Baillieres Clin Rheumatol 1994;8:333-62.

10. Toussirot E, Dupond JL, Wendling D. Spondylodiscitis in SAPHO syndrome. A series of eight cases. Ann Rheum Dis 1997;56:52-8.

11. Nachtigal A, Cardinal E, Bureau NJ, Sainte-Marie LG, Milette F. Vertebral involvement in SAPHO syndrome: MRI findings. Skeletal Radiol 1999;28:163-8.

Mycobacterium tuberculosis Infection of a Tophaceous Pseudogout Nodule

To the Editor:

I enjoyed the important case report by Santos-Ocampo, et al¹ showing supra-infection by mycobacteria of a calcific deposit in the finger. I would like to caution whether the calcific deposit was as definitely due to calcium pyrophosphate dihydrate (CPPD) crystals as described. The patient was young, had no family history of CPPD, had no risk factors described, and as a dialysis patient seemed more at risk for apatite [basic calcium phosphate (BCP)] deposition. Although CPPD can rarely cause tophus-like periarticular deposits², the radiographic pattern shown looks more like apatite. In addition, no typical cartilage calcifications were apparently noted. The microscopic examination described also raises concern, as the typical crystals were also noted to be associated with "lipid." Was this confirmed by fat stain? It seems possible that what were seen were the spherules typical of apatite, well described by McCarty and Gatter³ and illustrated in the Atlas of Synovial Fluid Analysis and Crystal Identification⁴. Some apatite or other BCP clumps can also be angular and might be mistaken for CPPD, if the spherules were not recognized. Although usually non-birefringent, these clumps can be faintly birefringent.

The authors obviously had thought about apatite but did not have the special stains available. Most pathology laboratories can do calcium stains, but reference laboratories, such as ours or Neil Mandel in Milwaukee, are usually delighted to help with puzzling cases. Might another aspiration be done? None of this is to detract from the basic observation, but to try to be certain about the exact association. There may also be implications for treatment of the calcifications.

H. RALPH SCHUMACHER Jr, MD, Professor of Medicine, University of Pennsylvania, Chief of Rheumatology, VA Medical Center, Philadelphia, Pennsylvania, USA.

REFERENCES

1. Santos-Ocampo AS, Tupasi TE, Villanueva F, Roxas FKA, Ramos CP. Mycobacterium tuberculosis infection of a tophaceous pseudogout nodule [case report]. J Rheumatol 2002;29:1093-6.

2. Li-Yu J, Schumacher HR, Gratwick G. Invasive tophaceous pseudogout in the temporomandibular joint: misdiagnosis as tumor. J Clin Rheumatol 2000;6:272-7.

3. McCarty DJ, Gatter RA. Recurrent acute inflammation associated with focal apatite crystal deposition. Arthritis Rheum 1966;9:804-19.

4. Schumacher HR, Reginato AJ. Atlas of synovial fluid analysis and crystal identification. Philadelphia: Lea & Febiger; 1991.

Dr. Santos-Ocampo replies

To the Editor:

We thank Dr. Schumacher for his interest in our case report. While we agree that basic calcium phosphate or apatite crystals could have contributed to the development of tophi in this patient, we also confirm that the aspirates of the right metacarpophalangeal and left elbow tophi did show an abundance of typical weakly positively birefringent rods consistent with calcium pyrophosphate dihydrate crystals. Certainly, both types of crystals could have coexisted in the same tophus. The lipids described in the fluid were not confirmed by fat staining. Most of the fluid obtained was sent for bacteriologic studies, and none are available for additional testing since the patient has died. We thank Dr. Schumacher for his generous offer to assist us in the future identification of apatite crystals. We will certainly request his assistance should a similar case present itself.

ALBERTO S. SANTOS-OCAMPO, MD, 190 Mabini Street, San Juan, Metro Manila 1500, Philippines.