Clinical rheumatology, 1992, 11, N ~ 3
371-375
Noninfectious Osteitis ' Part of the SAPHO Syndrome P.C.
VECCHIO,
P.V.
MARLTON,
J. W E B B
Summary
SAPHO, a rare syndrome, is a recently suggested acronym for synovitis, acne, pustulosis, hyperostosis and osteitis. It encompasses many features which have been described in different but overlapping conditions. Not all of the syndrome components need to be present for inclusion in SAPHO to be justified, especially the.dermatologic components. Two cases are described as examples. Clinicians should be aware of this rare disorder if positive early diagnoses are to be made in patients presenting with skeletal pain. Key words :
Noninfectious Osteitis, SAPHO.
CASE REPORTS
INTRODUCTION Cases of noninfectious osteitis have been reported from time to time for 20 years. They are usually chronic, often involve multiple bony sites and have been previously described under a variety of names, such as : inflammatory multifocal noninfectious osteitis, chronic recurrent multifocal osteomyelitis and pustulotic arthroosteitis (1-10). Although these syndromes are distinctly uncommon in Caucasians, they seem to be reported more frequently in Japan (1,2). Diagnosis is usually delayed due to the rarity of the disorder and the low index of suspicion in clinicians treating patients with these conditions. They have been known to be associated with an odd array of dermatoses including palmoplantar pustulosis and acne. The aetiology is uniformly obscure and the course is of unpredictable remission and exacerbation. These diseases are now considered to be sufficiently related to be grouped together under the acronym SAPHO (synovitis, ache, pustulosis, hyperostosis and osteitis (3). Characteristic rheumatologic manifestations include anterior chest wall involvement, axial skeleton lesions and osteitis of the appendicular bones; skin involvement is not essential. The following 2 cases are representative examples and illustrate clinical features that may alert one to the diagnosis.
Rheumatology Department, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Qld 4102, UK,
Case 1
A 20-year-old Caucasian female presented with a 16month history of variable bone pain initially involving the low back but subsequently affecting shoulders, sternum and bilateral ribs. There was also a 2-month history of anorexia, weight loss and lethargy. Other than a tender lump on the right fifth rib anteriorly and areas of bony tenderness corresponding to symptomatic loci, no further abnormal findings were noted. Initial workup revealed a mild normochromic anaemia with a haemoglobin of llg/dl (normal range 12-15g/dl) and erythrocyte sedimentation rate (ESR, Westergren) of 37 mm/hr (normal range < 10). Biochemical parameters were normal and the serum protein electrophoretic pattern was consistent with an acute phase reaction. Bone scan revealed multiple "hot spots" corresponding to areas of pain (Fig. 1). X-rays of relevant areas demonstrated an expanded mixed sclerotic/lytic lesion with defined margins on the right fifth rib anteriorly (Fig. 2) and sclerotic changes of the lumbar vertebrae. There was manubriosternal sclerosis (Fig. 3). Excision biopsies of the 2 affected ribs revealed nonspecific changes consistent with chronic inflammation. Marrow spaces were fibrotic with infiltrates of lymphocytes, plasma cells and neutrophils and showed prominent new bone formation. Further bone marrow aspiration and trephine biopsies were performed on other involved areas and were essentially normal. Extensive microbiological testing on these specimens as well as multiple blood cultures and serologic testing failed to implicate any causative organism. Occult malignancy was sought.
372
P.C. Vecchio, P.V. Marlton, J. W e b b
Fig. 1 : Technetium bone scan showing increased radionuclide uptake in ribs and manubriosternal joint.
Fig. 2 ." Lesion expanding fifth rib.
Noninfections osteitis
373
Fig. 3: Manubriosternal sclerosis with erosions of sclerotic subchondral bone.
Table I : Syndromes encompassed by SAPHO Chronic recurrent multifocal osteomyelitis CRMO Sternocostoclavicular hyperostosis SCCH Pustulotic arthro-osteitis PAO Palmoplantar pustulosis PPP Inflammatory multifocal noninfectious osteitis IMNO Hyperostosis, osteitis, periostitis HOP
CT scans of the thorax and abdomen were normal as was pelvic ultrasound. The patient's symptoms have fluctuated throughout the 3 years of observation with no overall progression. She remains adequately controlled on simple analgesia. Case 2
A 42-year-old Caucasian female complained for 20 years of painful swollen knees and neck, 15 years of painful sternoclavicular joints (left more than right) and 10 years of low back pain. H e r past history included endometriosis and right eye blindness secondary to operative removal of an optic nerve schwannoma. Examination revealed tender swollen sternoclavicular joints but was otherwise normal. Investigations included a normal full blood count and serum protein electrophoretic pattern, negative antinu-
clear antibodies, rheumatoid factor and H L A B27 and an ESR of 7 mm/hr (normal range < 10). Radiology of the pelvis and lumbar spine were normal and there was no sacroiliitis. Tomography of the sternoclavicular joints demonstrated a sclerotic sternal head of the left clavicle (Fig. 4). To date, her symptoms are largely unchanged over 5 years of observation despite intermittent anti-inflammatory drug therapy.
DISCUSSION These cases are part of the spectrum of SAPHO, which is of unknown aetiology. This term embraces many related syndromes (Table I) which are not widely reported in Western literature. The common denominator in each of these is the skeletal inflammatory process (4), heralding the merger into S A P H O (3). It is thought these conditions represent different but overlapping presentations of the same disorder and this is justified by several pieces of evidence. Reports from Japan have noted the definite relationship between palmoplantar pustulosis (a chronic eruption of yellowish sterile pustules on the palms and soles) and skeletal abnormalities including noninfectious vertebral and sacroiliac joint involvement, anterior chest wall disorders, peripheral os-
374
P.C. Vecchio, P.V. Marlton, J. Webb
Fig. 4: Sclerotic head of left clavicle with subchondral erosions.
teitis and arthritis (1,2). Sternocostoclavicular hyperostosis has been previously linked with palmoplantar pustulosis in adults (2,4), as has chronic recurrent multifocal osteomyelitis in children (5). Analyzing these reports, it seems clear there is sufficient overlap to allow SAPHO to be the descriptive encompassing term. SAPHO is rare and the incidence in Caucasians is unknown. Neither sex predominates and age of onset inconstantly varies between 5 and 50 with clusters of patients under 20 (4) and at middle age (1,3,9). Multiple osseous sites are involved, often recurrently, and lesions of the anterior chest wall are almost universal (1,2). Erosions, hyperostosis and fusion of the sternoclavicular joints and manubriosternal synchondrosis are fairly common (4). Lesions have been reported in most peripheral bones, and vertebral sclerosis, fusion and spondylodiscitis are described in addition to sacroiliitis (1,4-6). Major symptoms include pain and swelling and objective signs of inflammation may be evident. Inflammatory arthritis is typically nonerosive and oligoarticular (1) and may involve joints adjacent to bony inflammation ; it is usually short-lived and remits in 1 to 2 months. We do not believe that skin involvement is essential for inclusion into the syndrome; hence, the cases described herein. If present, this may take the form of palmoplantar pustulosis or alternatively appear as an ache-equivalent (5). Other symtomatology includes low-grade fever and mal-
aise (5) although systemic enquiry can be unremarkable (1). Investigations are largely nonspecific. Radiology of the affected area may be negative except for soft-tissue swelling and osteopaenia in acute cases (1) followed by a periosteal reaction and cortical thickening (7). With time, sclerosis may supervene and most lesions eventually heal with only residual bony thickening remaining (7). Histopathology of biopsied tissue shows neutrophil infiltration, osteoclasts and signs of bone resorption (6). This is later followed by lymphocytes, nonspecific granulomas, marrow fibrosis and new bone formation (1,3). There has never been a proven microbiological cause despite extensive search for an infectious agent (6,8). H L A B27 is not a feature (4,9), rheumatoid factor is absent and other blood parameters are not striking except occasionally a mildly raised erythrocyte sedimentation rate and alkaline phosphatase. The clinical course is marked by multiple remissions and exacerbations but the eventual outcome may be a permanent remission without major sequelae (5). Anti-inflammatory therapy with nonsteroidal agents is incompletely effective and no treatment has any demonstrable impact on the course or outcome (1,5). Notwithstanding the rarity of this disorder, diagnosis is possible if clinicians are aware of its existence. The prognosis is more favourable than many of the differential diagnoses in a patient with multiple
Noninfections osteitis
bony lesions such as disseminated malignancy and infection. Although positive exclusion of infection and malignancy is necessary, recognition of this syndrome allows
375
reassurance of the patient without the need for repetitive investigation. Acknowledgement : We would like to thank Dr. Kerry Taylor for allowing us to report one of his patients.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
Sonozaki, H., Mitsui, H., Miyanaga, Y., et al. Clinical features of 53 cases with pustulotic arthro-osteitis. Ann Rheum Dis 1981, 40, 547-553. Kawai, K., Doita, M., Tateishi, H., Hirohata, K. Bone and joint lesions associated with pustulosis et plantaris. J Bone Joint Surg 1988, 70-B, 117-22. Chamot, A.M., Benhamou, C.L., Kahn, M.F., Beraneck, L., Kaplan, G., Prost, A. Le syndrome acne pustulose hyperostose osteite (SAPHO). Rev Rhum Mal Osteoartic 1987, 54, 187-96. Fallet, G.H., Lagier, R., Gerster, J-C., Arroyo, J. Sternocostoclavicular hyperostosis (SCCHO) with palmoplantar pustulosis (PPP). Clin Exp Rheumatol 1987, 5, 135-41. Laxer, R.M., Shore, A.D., Manson, D., King, S., Silverman, E.D., Wilmot, D.M. Chronic recurrent multifocal osteomyelitis and psoriasis - a report of a new association and review of related disorders. Semin Arthritis Rheum 1988, 17, 260-70. Bjorksten, B., Boquist, L. Histopathological aspects of chronic recurrent multifocal osteomelitis. J Bone Joint Surg 1980, 62-B, 376-80. Probst, F.P., Bjorksten, B., Gustavson, K.H. Radiological aspects of chronic recurrent multifocal osteomyelitis. Ann Radiol 1978, 21, 115-25.
8.
Kozlowski, K., Beluffi, G., Feltham, C., James, M., Nespoli, L., Tamacia, L. Multifocal, chronic osteomyelitis of unknown aetiology. Forschr Rontgenstr 1985, 142, 440-6. 9. Huaux, J.P., Esselinckx, W., Meunier, H., Malghem, J., Maldague, C., Nanant de Deu• C. Pustulotic arthroosteitis in children and adults. A report of 13 cases. Clin Exp Rheumatol 1987, 5, 143-6. 10. Fournie, A., Bouvier, M., Fournie, B., Colson, F., Ayrolles, C., Larbre, J.P. Hyperostose- osteite- periostite. Triade radiologique des enthesopathies. Remarques a p r o p o s de deux localisations femorales inhabituelles. Rev Rhum Mal Osteoartic 1989, 56, 763766.
Received : 4 November 1991 ; Revision-accepted : 22 December 1991 Correspondence to: P.C. VECCHIO, Rheumatology Research Unit E6, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK.
371-375
Noninfectious Osteitis ' Part of the SAPHO Syndrome P.C.
VECCHIO,
P.V.
MARLTON,
J. W E B B
Summary
SAPHO, a rare syndrome, is a recently suggested acronym for synovitis, acne, pustulosis, hyperostosis and osteitis. It encompasses many features which have been described in different but overlapping conditions. Not all of the syndrome components need to be present for inclusion in SAPHO to be justified, especially the.dermatologic components. Two cases are described as examples. Clinicians should be aware of this rare disorder if positive early diagnoses are to be made in patients presenting with skeletal pain. Key words :
Noninfectious Osteitis, SAPHO.
CASE REPORTS
INTRODUCTION Cases of noninfectious osteitis have been reported from time to time for 20 years. They are usually chronic, often involve multiple bony sites and have been previously described under a variety of names, such as : inflammatory multifocal noninfectious osteitis, chronic recurrent multifocal osteomyelitis and pustulotic arthroosteitis (1-10). Although these syndromes are distinctly uncommon in Caucasians, they seem to be reported more frequently in Japan (1,2). Diagnosis is usually delayed due to the rarity of the disorder and the low index of suspicion in clinicians treating patients with these conditions. They have been known to be associated with an odd array of dermatoses including palmoplantar pustulosis and acne. The aetiology is uniformly obscure and the course is of unpredictable remission and exacerbation. These diseases are now considered to be sufficiently related to be grouped together under the acronym SAPHO (synovitis, ache, pustulosis, hyperostosis and osteitis (3). Characteristic rheumatologic manifestations include anterior chest wall involvement, axial skeleton lesions and osteitis of the appendicular bones; skin involvement is not essential. The following 2 cases are representative examples and illustrate clinical features that may alert one to the diagnosis.
Rheumatology Department, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Qld 4102, UK,
Case 1
A 20-year-old Caucasian female presented with a 16month history of variable bone pain initially involving the low back but subsequently affecting shoulders, sternum and bilateral ribs. There was also a 2-month history of anorexia, weight loss and lethargy. Other than a tender lump on the right fifth rib anteriorly and areas of bony tenderness corresponding to symptomatic loci, no further abnormal findings were noted. Initial workup revealed a mild normochromic anaemia with a haemoglobin of llg/dl (normal range 12-15g/dl) and erythrocyte sedimentation rate (ESR, Westergren) of 37 mm/hr (normal range < 10). Biochemical parameters were normal and the serum protein electrophoretic pattern was consistent with an acute phase reaction. Bone scan revealed multiple "hot spots" corresponding to areas of pain (Fig. 1). X-rays of relevant areas demonstrated an expanded mixed sclerotic/lytic lesion with defined margins on the right fifth rib anteriorly (Fig. 2) and sclerotic changes of the lumbar vertebrae. There was manubriosternal sclerosis (Fig. 3). Excision biopsies of the 2 affected ribs revealed nonspecific changes consistent with chronic inflammation. Marrow spaces were fibrotic with infiltrates of lymphocytes, plasma cells and neutrophils and showed prominent new bone formation. Further bone marrow aspiration and trephine biopsies were performed on other involved areas and were essentially normal. Extensive microbiological testing on these specimens as well as multiple blood cultures and serologic testing failed to implicate any causative organism. Occult malignancy was sought.
372
P.C. Vecchio, P.V. Marlton, J. W e b b
Fig. 1 : Technetium bone scan showing increased radionuclide uptake in ribs and manubriosternal joint.
Fig. 2 ." Lesion expanding fifth rib.
Noninfections osteitis
373
Fig. 3: Manubriosternal sclerosis with erosions of sclerotic subchondral bone.
Table I : Syndromes encompassed by SAPHO Chronic recurrent multifocal osteomyelitis CRMO Sternocostoclavicular hyperostosis SCCH Pustulotic arthro-osteitis PAO Palmoplantar pustulosis PPP Inflammatory multifocal noninfectious osteitis IMNO Hyperostosis, osteitis, periostitis HOP
CT scans of the thorax and abdomen were normal as was pelvic ultrasound. The patient's symptoms have fluctuated throughout the 3 years of observation with no overall progression. She remains adequately controlled on simple analgesia. Case 2
A 42-year-old Caucasian female complained for 20 years of painful swollen knees and neck, 15 years of painful sternoclavicular joints (left more than right) and 10 years of low back pain. H e r past history included endometriosis and right eye blindness secondary to operative removal of an optic nerve schwannoma. Examination revealed tender swollen sternoclavicular joints but was otherwise normal. Investigations included a normal full blood count and serum protein electrophoretic pattern, negative antinu-
clear antibodies, rheumatoid factor and H L A B27 and an ESR of 7 mm/hr (normal range < 10). Radiology of the pelvis and lumbar spine were normal and there was no sacroiliitis. Tomography of the sternoclavicular joints demonstrated a sclerotic sternal head of the left clavicle (Fig. 4). To date, her symptoms are largely unchanged over 5 years of observation despite intermittent anti-inflammatory drug therapy.
DISCUSSION These cases are part of the spectrum of SAPHO, which is of unknown aetiology. This term embraces many related syndromes (Table I) which are not widely reported in Western literature. The common denominator in each of these is the skeletal inflammatory process (4), heralding the merger into S A P H O (3). It is thought these conditions represent different but overlapping presentations of the same disorder and this is justified by several pieces of evidence. Reports from Japan have noted the definite relationship between palmoplantar pustulosis (a chronic eruption of yellowish sterile pustules on the palms and soles) and skeletal abnormalities including noninfectious vertebral and sacroiliac joint involvement, anterior chest wall disorders, peripheral os-
374
P.C. Vecchio, P.V. Marlton, J. Webb
Fig. 4: Sclerotic head of left clavicle with subchondral erosions.
teitis and arthritis (1,2). Sternocostoclavicular hyperostosis has been previously linked with palmoplantar pustulosis in adults (2,4), as has chronic recurrent multifocal osteomyelitis in children (5). Analyzing these reports, it seems clear there is sufficient overlap to allow SAPHO to be the descriptive encompassing term. SAPHO is rare and the incidence in Caucasians is unknown. Neither sex predominates and age of onset inconstantly varies between 5 and 50 with clusters of patients under 20 (4) and at middle age (1,3,9). Multiple osseous sites are involved, often recurrently, and lesions of the anterior chest wall are almost universal (1,2). Erosions, hyperostosis and fusion of the sternoclavicular joints and manubriosternal synchondrosis are fairly common (4). Lesions have been reported in most peripheral bones, and vertebral sclerosis, fusion and spondylodiscitis are described in addition to sacroiliitis (1,4-6). Major symptoms include pain and swelling and objective signs of inflammation may be evident. Inflammatory arthritis is typically nonerosive and oligoarticular (1) and may involve joints adjacent to bony inflammation ; it is usually short-lived and remits in 1 to 2 months. We do not believe that skin involvement is essential for inclusion into the syndrome; hence, the cases described herein. If present, this may take the form of palmoplantar pustulosis or alternatively appear as an ache-equivalent (5). Other symtomatology includes low-grade fever and mal-
aise (5) although systemic enquiry can be unremarkable (1). Investigations are largely nonspecific. Radiology of the affected area may be negative except for soft-tissue swelling and osteopaenia in acute cases (1) followed by a periosteal reaction and cortical thickening (7). With time, sclerosis may supervene and most lesions eventually heal with only residual bony thickening remaining (7). Histopathology of biopsied tissue shows neutrophil infiltration, osteoclasts and signs of bone resorption (6). This is later followed by lymphocytes, nonspecific granulomas, marrow fibrosis and new bone formation (1,3). There has never been a proven microbiological cause despite extensive search for an infectious agent (6,8). H L A B27 is not a feature (4,9), rheumatoid factor is absent and other blood parameters are not striking except occasionally a mildly raised erythrocyte sedimentation rate and alkaline phosphatase. The clinical course is marked by multiple remissions and exacerbations but the eventual outcome may be a permanent remission without major sequelae (5). Anti-inflammatory therapy with nonsteroidal agents is incompletely effective and no treatment has any demonstrable impact on the course or outcome (1,5). Notwithstanding the rarity of this disorder, diagnosis is possible if clinicians are aware of its existence. The prognosis is more favourable than many of the differential diagnoses in a patient with multiple
Noninfections osteitis
bony lesions such as disseminated malignancy and infection. Although positive exclusion of infection and malignancy is necessary, recognition of this syndrome allows
375
reassurance of the patient without the need for repetitive investigation. Acknowledgement : We would like to thank Dr. Kerry Taylor for allowing us to report one of his patients.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
Sonozaki, H., Mitsui, H., Miyanaga, Y., et al. Clinical features of 53 cases with pustulotic arthro-osteitis. Ann Rheum Dis 1981, 40, 547-553. Kawai, K., Doita, M., Tateishi, H., Hirohata, K. Bone and joint lesions associated with pustulosis et plantaris. J Bone Joint Surg 1988, 70-B, 117-22. Chamot, A.M., Benhamou, C.L., Kahn, M.F., Beraneck, L., Kaplan, G., Prost, A. Le syndrome acne pustulose hyperostose osteite (SAPHO). Rev Rhum Mal Osteoartic 1987, 54, 187-96. Fallet, G.H., Lagier, R., Gerster, J-C., Arroyo, J. Sternocostoclavicular hyperostosis (SCCHO) with palmoplantar pustulosis (PPP). Clin Exp Rheumatol 1987, 5, 135-41. Laxer, R.M., Shore, A.D., Manson, D., King, S., Silverman, E.D., Wilmot, D.M. Chronic recurrent multifocal osteomyelitis and psoriasis - a report of a new association and review of related disorders. Semin Arthritis Rheum 1988, 17, 260-70. Bjorksten, B., Boquist, L. Histopathological aspects of chronic recurrent multifocal osteomelitis. J Bone Joint Surg 1980, 62-B, 376-80. Probst, F.P., Bjorksten, B., Gustavson, K.H. Radiological aspects of chronic recurrent multifocal osteomyelitis. Ann Radiol 1978, 21, 115-25.
8.
Kozlowski, K., Beluffi, G., Feltham, C., James, M., Nespoli, L., Tamacia, L. Multifocal, chronic osteomyelitis of unknown aetiology. Forschr Rontgenstr 1985, 142, 440-6. 9. Huaux, J.P., Esselinckx, W., Meunier, H., Malghem, J., Maldague, C., Nanant de Deu• C. Pustulotic arthroosteitis in children and adults. A report of 13 cases. Clin Exp Rheumatol 1987, 5, 143-6. 10. Fournie, A., Bouvier, M., Fournie, B., Colson, F., Ayrolles, C., Larbre, J.P. Hyperostose- osteite- periostite. Triade radiologique des enthesopathies. Remarques a p r o p o s de deux localisations femorales inhabituelles. Rev Rhum Mal Osteoartic 1989, 56, 763766.
Received : 4 November 1991 ; Revision-accepted : 22 December 1991 Correspondence to: P.C. VECCHIO, Rheumatology Research Unit E6, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ, UK.
