Sapho syndrome about 12 cases and literature review

Download 52.53 Kb.
Date conversion31.01.2017
Size52.53 Kb.
SAPHO syndrome about 12 cases and literature review

Gharsallah .I1 , Souissi A2, Métoui .L1, R Dhahri1, N Boussetta1 , S Sayhi1, S youssef2 ,

N ben abdelhafidh 1, F Agili1

1Department of Internal Medicine at the Military Hospital

2Department of Dermatology of the Tunis military hospital


Background: SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is a rare entity that designates the combination of a heterogeneous set of skin and musculoskeletal manifestations.

Objective: To describe the clinical, biological, radiological and therapeutic alternatives in SAPHO syndrome.

Materials and Methods: This is a retrospective study of all patients admitted in our clinic between 1995 and 2012 and have met the diagnostic criteria of SAPHO syndrome. We recorded: age, sex, bone and joint locations , skin lesions and response to treatment . The results of laboratory tests, radiological and bone scan were recorded.

Results: Twelve patients whose average age was 33 years met the criteria of SAPHO syndrome. Skin lesions were observed in 7 cases. The anterior chest wall and spine were the most frequent osteoarticular sites. NSAIDs prescribed first line in all patients were effective in 7 cases. Other treatments were administered in 5 patients: sulfasalazine (4 cases), methotrexate (3 cases), intravenous pamidronate (1 case) and etanercept (1 case).

Conclusions: Early recognition SAPHO syndrome avoids invasive complementary tests and unnecessary treatment. NSAIDs are the most frequently used treatment, but they may be ineffective. Intravenous pamidronate and anti TNF alpha are promising treatments.

SAPHO syndrome ( synovitis , acne, pustulosis , hyperostosis , osteitis ) is a rare entity that was first described by Chamot in 1987. It refers to the combination of a heterogeneous set of skin and musculoskeletal manifestations whose common denominator an inflammatory process is aseptic. The etiology of SAPHO syndrome remains mysterious. Nonsteroidal antiinflammatory drugs (NSAIDs) have for many years the first-line treatment of musculoskeletal manifestations. Currently, the syndrome has been considerable therapeutic progress especially with the advent of bisphosphonates and anti TNF alpha.

Goal: The aim of our work is to support the different epidemiological, clinical, biological, radiological, treatment and outcome of this syndrome.

Material and methods

This is a retrospective study of twelve patients admitted to the Internal Medicine Department of the Main Military Hospital of Tunis instruction over a period of 17 years from 1995 to 2012.

We included the study of all patients meeting the criteria of Khan 1994 (Table 1).

1- epidemiological data: age, gender, personal history, family history of skin disease or inflammatory arthritis.

2. clinical data: including data from the anamnesis (age, functional signs), the musculoskeletal and skin examination looking for axial involvement, anterior chest wall or joint device.

3- biological data: complete blood count, erythrocyte sedimentation rate, C reactive protein (CRP), HLA typing.

4- the imaging data: based on analysis

 standard radiographs of the thoracolumbar spine, pelvis and focused on the sacroiliac

 bone scintigraphy (before and after treatment)

 computed tomography (CT) of the anterior chest wall and sacroiliac, whenever the standard radiographs were inconclusive.

 magnetic resonance imaging (MRI) spinal.

5- therapeutic modalities

 physical treatment: respiratory gymnastics and spinal associated with peripheral joints rehabilitation in case of limited joint mobility.

 medical treatment: symptomatic treatments (analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and DMARDs (sulfasalazine, methotrexate (MTX), bisphosphonates and anti-TNFa).

6- evolution

Treatment efficacy was judged on the regression of cutaneous lesions, visual analogue scale (VAS) pain, tender joint count and on the inflammatory balance (ESR, CRP). Functional indices (BASFI) and activity indices (BASDAI) were performed in 4 patients that this has limited their use as evaluation criteria.


1- Epidemiological data

Our study included 12 patients. The sex ratio was 1. The mean age of patients was 33 years, ranging from 20 to 60 years. Seven patients were aged under 40 (histogram 1). One male patient with a positive HLA B27 typing reported a history of spondyloarthritis in the family. In another patient, a drop in psoriasis was noted in the brother. The delay means the diagnosis was 5 years with extremes ranging from 1 month to 29 years. The consultation delay and absence of cutaneous signs in the early stages of the disease were responsible.

2- Clinical data:

The clinical signs associated skin and bone joint.

 The cutaneous signs:

PPP was found in 5 cases; acne was observed in two cases (one patient had both a PPP and acne). No cutaneous signs were observed in 5 patients.

 Osteoarticular signs were distributed as shown in the diagram 1.

 Fever was absent in the status stage in all patients. Fatigue was reported in all patients.

 No other particular digestive systemic event (abdominal pain, diarrhea or rectal bleeding) were noted in our series.

3- Biological data:

The average value of the VS in the first hour was 50 mm, with a range from 20 to 90.

The mean CRP was 33 mg / l. It was greater than 6 mg / l in 8 patients.

Inflammatory anemia was observed in 1 case. It was 10 g / dl.

None of our patients had elevated PAL.

The HLA B27 was performed in 10 patients. It was positive in 3 cases.

3- imagery data: In Table 2 are shown the results of imaging.

4- histopathological data

Antibiotic doxycycline at a dose of 200 mg / day for 3 months was required in 3 cases (it was osteitis left elbow in 1 case and infringement of the anterior chest wall resistant NSAIDs in 2 cases).

Sulfasalazine has been used in four cases before the non improving musculoskeletal symptoms as symptomatic treatment. The dose was 2 g / day for an average term of 4 years.

MTX was prescribed in 3 cases before a polyarthritis resistant to NSAIDs and sulfasalazine. The dose was 15 mg / week for an average of 2 years.

Intravenous pamidronate was used at a dose of 60 mg / day for three consecutive days in a patient aged 32 who presented with arthritis of the reaction left elbow osteitis radial head having resisted the different treatments (NSAIDs, ATB, sulfasalazine and MTX).

Etanercept was prescribed at a dose of 25 mg x 2 / week in one patient aged 51 with arthritis and a violation of the anterior chest wall resistant to different treatments (NSAIDs, ATB, sulfasalazine and MTX).

6- scalable data:

The decline was an average of 48 months in our study.

The evolution was marked by the occurrence of outbreaks interspersed with intervals of remission in all patients.

Symptomatic treatment with analgesics and NSAIDs was adequate in 7 cases with almost complete regression of musculoskeletal symptoms after an average period of 24 months.

Treatment with doxycycline in 3 patients with involvement of the anterior chest wall was no profit. The prescription of a DMARD was necessary in 3 cases.

Sulfasalazine has been prescribed in 4 cases. It was effective in 2 cases with regression of musculoskeletal symptoms after an average period of 36 months. It was ineffective in the other two cases.

MTX was prescribed in 3 cases. The improvement was clear on the skin and musculoskeletal plan 1 single case while the other two patients had resisted MTX what led us to prescribe pamidronate in one and etanercept in another.

A dramatic improvement was observed after one pamidronate treatment in the patient with osteomyelitis of the left elbow.

Etanercept was effective with total regression of musculoskeletal symptoms after 12 months of treatment.

For skin disease, the lesions regressed under local treatment.

No adverse effects related to the different treatments used were noted in our patients.


SAPHO syndrome is included by many authors under spondylarthropathies seen frequent reached entheses, the association with inflammatory bowel disease and the presence of the HLA-B27 antigen in 13-30% of cases [2, 3, 4] against 8% in the general population.

The pathogenesis of SAPHO syndrome remains mysterious. P. acnes, Corynebacterium commensal of the sebaceous glands and hair follicles was isolated within the joint and bone damage in many series in the literature [4, 5, 6] with a variable frequency up to 67% of cases in the series Assman. [7] This infectious origin is confirmed by the significant improvement that have achieved some teams opting for prolonged treatment with tetracyclines[8,9] or azithromycin [1, 6]. On the other hand, a German team has recently highlighted the role of proinflammatory cytokines in this syndrome. Indeed, they were able to demonstrate the presence of a strong expression of tumor necrosis factor (TNF) in a lesion mandibular osteomyelitis [10, 11].

The results of our study and in comparison to the latest series join the data in the literature in several points: the paucity of SAPHO syndrome (12 cases in 17 years), sex ratio of 1, the prevalence among subjects age young and Non-infringement of skin in about a third of cases.

Clinically, the main cutaneous manifestations encountered in SAPHO syndrome are the PPP, severe acne in its three forms (acne conglobata, hidradenitis suppurativa and acne fulminans) and psoriasis. The PPP is more common in patients over 30 years and in particular female while acne would be among men under 30 years [2]. Also other skin lesions are more and more frequently described in SAPHO syndrome as pyoderma gangrenosum [12, 13] or the Sweet syndrome [14, 15].

On the osteoarticular level, anterior chest wall is the most frequently affected through literature location. It is seen in 65-90% of cases [16]. Involvement of the spine is less common (32-52% of cases). It is segmented and can reach three stories spine [1, 17]. The thoracic spine is most affected. In our series, in contrast to the literature, spinal involvement was more common than the involvement of the anterior chest wall.

The achievement of the sacroiliac is most often asymptomatic and radiological discovery may manifest inflammatory fessialgies sometimes having a root path L5 or S1.

Radiologically, the sensitivity of standard radiographs is low. Fritz showed that they only detect 16% of lesions early objectified by MRI [18]. However, enthesopathy costo-clavicular hyperostosis and a home of at least 5 mm in diameter at the sternum or upper ribs are highly suggestive signs of SAPHO syndrome. [19] Sacroiliitis is distinguished by its frequently unilateral nature and its association with hyperostosis [3, 20, 21]. As for spinal disease, it can lead to aspects of condensing osteitis of paraspinal ossification, spondylitis and sometimes vertebral fractures [22]. CT remains the gold standard for exploring the anterior chest wall and in particular the achievement of sternocostoclavicular joints [5, 20]. It also allows early detection of clinically silent areas and standard radiographs at the sacroiliac joints and spine.

However, MRI is superior to CT in the detection of joint damage and soft tissue [22]. It also, by its performance in the exploration enthesis, to establish a correlation between the stage of disease (or inflammatory sequelae phase) and clinical symptoms. It can also demonstrate the effectiveness of the treatment since the remission is accompanied by restoration of normal fat signal from the bone marrow [22].

Bone scan allows an early stage to map all bone and joint injuries even those ignored by CT and MRI. In our study, it was performed in 11 cases and was contributory in any case. We also used the scan to assess the effectiveness of treatment, but it seems clear that the use of MRI as a monitoring tool is better since saving the patient radiation exposure. [23]

Bone biopsy, performed in atypical forms, provides no specific elements of SAPHO syndrome but it is crucial in allowing especially if single lesion to eliminate an infectious or tumor pathology. In our series, only one patient had a bone biopsy before the suspicion of metastases. It showed a pseudopagétoide appearance already described by some authors in this syndrome [24, 25].

Therapeutically, NSAIDs have long constituted the reference symptomatic treatment. [26] Their effectiveness is considered partial and transient. In our study, they were effective in 7 cases.

Colchicine has been used by some teams in case of intolerance to NSAIDs but without benefit [2, 27]. Corticosteroid therapy is a good treatment alternative especially in the case of SAPHO syndrome with Sweet's syndrome [15] or associated with chronic inflammatory diseases [2] intestine. Cyclins and macrolides used long term treatments in 6 weeks to 3 months of separate therapeutic window of 1 to 2 months were effective [1,6, 8, 9] in some particular series in case of isolation of P. acnes. In our study, no improvement has been noted in three patients started on doxycycline. Sulfasalazine has been used by Edlund [4] and Johnston [28] with good results.

Methotrexate was also prescribed in a dose of between 7.5 and 15 mg / week with varying results [30, 31]. Its efficacy is proven in the treatment of PPP. [32] Currently, the SAPHO syndrome has experienced considerable therapeutic progress with the advent of bisphosphonates and anti TNF alpha. Pamidronate, known for its anti-inflammatory and antiostéoclastique action is an interesting alternative in cases resistant to standard treatments and a way to reduce the doses of anti-inflammatories and analgesics. Amital et al tried pamidronate in 10 patients with SAPHO syndrome. Nine patients were good responders. Eight more have need of a cure (60 mg per treatment): 2 courses in 5 cases, 3 cures in 1 case and 4 courses in 2 cases. Remission was complete in 6 patients and partial in the other three patients [33]. Among our patients, a dramatic improvement was achieved after a course of intravenous pamidronate in the patient with osteomyelitis of the left elbow.

Anti TNF alpha blocking the effector cytokine and major regulatory (TNF alpha) have proven effective in severe and refractory. Infliximab is the biological agent which is most prescribed at a dose of 5mg / kg (S0, S2, S6 and every 6 weeks). A literature review conducted by Moll brought together all cases refractory to conventional treatments SAPHO syndrome treated with infliximab. There were 17 patients (5 men and 12 women). All had musculoskeletal manifestations. Skin involvement was present in 78% of cases. Twelve patients (66%) responded to treatment after the first infliximab treatment and 4 others (22%) responded after the second treatment. Skin involvement, especially acne has been responsive to infliximab in 70% of cases. A switch with etanercept has been achieved in a case before the occurrence of bronchospasm. The outcome was favorable. [10]

Indeed, etanercept was used less frequently than infliximab in SAPHO syndrome but it was deemed effective in all cases reported in the literature (10, 35). In our series, it was prescribed in a patient who resisted methotrexate and sulfasalazine with total regression of musculoskeletal symptoms after 12 months of treatment.

Evolutionarily, SAPHO syndrome is a chronic disease that evolves in spurts interspersed with shorter or longer periods of remission.

Colina et al consider that some clinical and biological elements, namely the female, the involvement of the anterior chest wall, the presence of peripheral arthritis, skin lesions, or an inflammatory syndrome in early disease are factors predictive of chronic evolution and prolonged disease [25].


At the end of our study has certain limitations related to the number of these patients, in retrospective, single-center nature, we highlight some key points:

 Before cutaneous signs such as severe acne or PPP, one should look for signs of bone and joint, especially at the anterior chest wall and ask the slightest doubt a bone scan.

 Ask in time diagnosis of SAPHO syndrome can avoid unnecessary explorations and the use of inadequate treatment.

 The advent of bisphosphonates and anti TNF alpha is a therapeutic advance in SAPHO syndrome. Do not delay to prescribe in forms resistant to other treatments including osteitis.

 A multidisciplinary collaboration (dermatologist, rheumatologist, internist, radiologist) is necessary for an overall management of SAPHO syndrome.

1- Kahn MF, Kahn MA. The SAPHO syndrome. Baillier’s Clin Rheum 1994;8:333-62.
2- Hayem G, Bouchaud-Chabot A, Benali K et al. SAPHO syndrome: a longterm follow-up study of 120 cases. Semin Arthritis Rheum 1999; 29:159–71.
3- Chamot AM, Benhamou CL, Kahn MF, Beraneck L, Kaplan G, Prost A. Le syndrome synovite, acné, pustulose, hyperostose, osteite (SAPHO). Résultats d’une enquête nationale:85 observations. Rev Rhum Mal Osteoartic 1987; 54:187-96.
4- Edlund E, Johnsson U, Lidgren L et al. Palmoplantar pustulosis and sternoclavicular arthro-osteitis. Ann Rheum Dis 1988; 47:809-15

5- Reith JD, Bauer TW, Schils JP. Osseous manifestations of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Am J Surg Pathol 1996; 20:1368-77.

6- Kirchhoff T, Merkesdal S, Rosenthal H et al. Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up. Eur Radiol 2003; 13:2304-8.
7- Assmann G, Kueck O, Kirchhoff T et al. Efficacy of antibiotic therapy for SAPHO syndrome is lost after its discontinuation: interventional study. Arthritis Res Ther 2009; 11:140.
8- Govoni M, Colina M, Massara A, Trotta F. SAPHO syndrome and infections. Autoimmunity 2009; 8:256-9.
9- Ballara SC, Siraj QH, Maini RN, Venables PJ. Sustained response to doxycycline therapy in two patients with SAPHO syndrome. Arthritis Rheum 1999; 2:819–21.
10- Wagner AD, Andersen J, Jendro MC, Hulsemann JL, Zeidler H. Sustained response to tumor necrosis factor alpha blocking agents in two patients with SAPHO syndrome. Arthritis Rheum 2002; 46:1965-8.
11- Olivieri I, Padula A, Ciancio G, Salvarani C, Niccoli L, Cantini F. Successful treatment of SAPHO syndrome with infliximab: report of two cases.

Ann Rheum Dis 2002; 61:375-6.

12- Yamasaki O, Iwatsuki K, Kaneko F. A case of SAPHO syndrome with pyoderma gangrenosum and inflammatory bowel disease masquerading as Behcet’s disease.

Adv Exp Med Biol 2003; 528:339-41.

13- Edwards TC, Stapleton B, Bond MJ, Barrett FF. Sweet’s syndrome with multifocal sterile osteomyelitis. Am J Dis Child 1986; 140:817-8.
14- Beretta-Piccoli BC, Sauvin MJ, Gal I et al. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in childhood: a report of ten cases and review of the literature. Eur J Pediatr 2000; 159:594-601.
15- Edwards TC, Stapleton B, Bond MJ, Barrett FF. Sweet’s syndrome with multifocal sterile osteomyelitis. Am J Dis Child 1986; 140:817-8.
16- 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.
17- Toussirot E, Dupond JL, Wendling D. Spondylodiscitis in SAPHO syndrome. A series of eight cases. Ann Rheum Dis 1997; 56:52–8.
18- Fritz J, Tzaribatchev N, Claussen CD et al. Chronic recurrent multifocal osteomyelitis: comparison of whole-body MR imaging with radiography and correlation with clinical and laboratory data. Radiology 2009; 252:842-51.
19- Maugars Y, Berthelot JM, Ducloux JM, Prost A. SAPHO syndrome: a followup study of 19 cases with special emphasis on enthesis involvement. J Rheumatol 1995; 22:2135-41.
20- Sonozaki H, Mitsui H, Miyanaga YO et al. Clinical features of 53 cases with pustulotic arthroosteitis. Ann Rheum Dis 1981; 40:547-53.
21- Parlier-Cuau C, Laredo JD. Atteinte vertébrale du SAPHO. J Radiol 2010; 91:1068-78.
22- Laredo JD, Vuillemin- Bodaghi V, Boutry N, Cotton A, Parlier-Cuau C. SAPHO syndrome: MR appearance of vertebral involvement. Radiology 2007; 242: 825-31.

23- Bjorkstén B, Boquist L. Histopathological aspects of chronic recurrent multifocal osteomyelitis. J Bone Joint Surg Br 1980; 62:376-80.

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

25- Colina M, Govoni M, Orzincolo C, Trotta F. Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a single center study of a cohort of 71 subjects. Arthritis Rheum 2009; 61:813-21.

26- Levesque RY, Brassard A. Syndrome d’hyperostose acquise. Union Med Can 1993; 72 :254.

27- Johnston KA, Elston DM. Palmoplantar pustulosis associated with sternocostoclavicular hyperostosis. Cutis 1998; 62:75-6.

28- Cabay JE, Marcelis S, Dondelinger KF. La spondilodiscite inflammatoire comme manifestation radiologique unique du SAPHO. J Radiol 1998; 79:337-40.

29- Chamot AM, Vion B, Gerster JC. Acute pseudoseptic arthritis and palmoplantar pustulosis. Clin Rheumatol 1986; 5:118-23.
30- Ferguson PJ, Chen S, Tayeh MK et al. Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoetic anaemia (Majeed syndrome).

J Med Gent 2005; 42:551-7.

31- Zhao Z, Li Y, Li Y, Zhao H, Li H. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with review of the relevant published work. J Dermatol 2011; 38:155-9.

32- Amital H, Applbaum YH, Aamar S, Daniel N, Rubinow A. SAPHO syndrome treated with pamidronate: an open-label study of 10 patients. Rheumatology 2004; 43:658–61.

33- Vilar-Alejo J, Dehesa L, de la Rosa-del Rey Pet al. SAPHO syndrome with unusual cutaneous manifestations treated successfully with etanercept. Acta Derm Venereol 2010; 90:531-2.

34- Freyschmidt J, Kasperczyk. A The "bull horn sign" scintigraphic pattern in sternocostoclavicular hyperostosis and pustular arthro-osteitis. Z Rheumatol 1997; 56:136-43.

The database is protected by copyright © 2016
send message

    Main page