Exceptional response of skin symptoms to secukinumab treatment in a patient with SAPHO syndrome: Case report and literature review

Rationale:SAPHO syndrome is a rare clinical entity characterized by a wide range of dermatological and musculoskeletal manifestations. Treatment strategies are not standardized. Palmoplantar pustulosis (PPP) is the most common rash in patients with SAPHO syndrome.Patient concerns:A 24-year-old Chinese woman with no relevant medical or familial history had a 1-year history of cutaneous lesions with PPP and pain in the sternoclavicular joint.Diagnosis:Based on the diagnostic criteria for SAPHO syndrome proposed by Nguyen et al in 2012, we diagnosed SAPHO syndrome with severe PPP as the predominant manifestation.Interventions:Due to the limited therapeutic efficacy of methotrexate and cyclosporin, we started therapy with subcutaneous secukinumab 150 mg weekly for the first month, then 150 mg monthly thereafter.Outcomes:After 4 weeks of secukinumab administration, the patient showed significant remission of pustular skin lesions, with almost no joint pain and no adverse reaction. Complete remission of skin symptoms was achieved after 3 months. Joint pain and adverse events have not reoccurred in follow-up thus far.Conclusions:In patients with SAPHO syndrome, we recommend personalized treatment, which may have excellent therapeutic efficacy in those with PPP or severe skin symptoms. Although data related to the use of IL-17 blockers for SAPHO syndrome are very limited, secukinumab provides a novel therapeutic option, especially for patients with PPP and severe skin lesions. Further prospective studies are needed to support our findings.     

SAPHO syndrome or psoriatic arthritis? A familial case study.

OBJECTIVE: To discuss the relationships between SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome and the group of spondylarthropathies. METHODS: Few reports of familial SAPHO have been published. We describe three children, two sisters and one brother, whose clinical and radiological presentation was in accordance with SAPHO syndrome. RESULTS: Two children developed psoriasis, and one child palmoplantar pustulosis. Both sacroiliac and sternoclavicular joints were involved in these three cases. Some features in our observations are also common to psoriatic arthritis. No association was found with HLA antigens, but a history of trauma preceding the onset of symptoms was present in all three children. CONCLUSIONS: We can consider that SAPHO is nosologically related to spondylarthropathies. Psoriatic arthritis could be the missing link between SAPHO and spondylarthropathies. It is likely that both genetic and environmental factors are involved.     

Synovitis,acne, pustulosis,hyperostosis, osteitis (SAPHO), and chronic recurrent multifocal osteomyelitis (CRMO): A tale of two cases

BackgroundSAPHO (Synovitis Acne Pustulosis Hyperostosis Osteitis) and CRMO (Chronic Recurrent Multifocal Osteomyelitis) are chronic relapsing osteoarticular disorders with common dermatological manifestations.Aim of the workTo describe a case of SAPHO in an adult and CRMO in a child.Cases presentationCase 1: A 32-year old man presented with dull aching low back pain for 2 years with morning pain/stiffness. On examination there were acneform lesions on the face, tenderness over thoracic spine and swelling of left sternoclavicular joint. Plain x-rays showed sclerosis/widening/irregularity of sternoclavicular joint, sclerosis/irregularity of endplate, loss of disc space with syndesmophytes in mid/lower dorsal spine (D6-11) and sclerosis in middle of left tibia. Magnetic resonance imaging (MRI) spine showed cortical erosions and marrow edema (D6-L1) with findings suggestive of aseptic/inflammatory spondylodiscitis. A bone scan showed increased uptake D7-D12 and mid-third tibia (hyperostosis). Biopsy from D6/D7 showed normal histopathology. Case 2: A 10-year-old girl presented with pain/swelling of right foot for 2 months, pain/swelling of left shoulder and sternoclavicular joint with pustular acne on the face. There was swelling/tenderness over right 5th metatarsal base and left sternoclavicular joint as well as tenderness over proximal humerus. ESR was 65 mm/1^sthr. Plain x-rays showed punched-out lytic lesions surrounded by sclerosis in metatarsal base and metaphysis of humerus. Patient was diagnosed as CRMO.ConclusionSAPHO and CRMO are rare and their diagnosis is sometimes not easy. SAPHO can present as aseptic spondylodiscitis. Both conditions can be diagnosed with clinical and radiological features. A biopsy is necessary for ruling out other conditions.     

Pulmonary adenocarcinoma associated with SAPHO syndrome difficult to differentiate from multiple bone metastasis

The patient was a 57-year-old man with a chief complaint of anterior chest pain who was diagnosed with clinical stage IV (c-T2N2M1) non-small-cell lung cancer (adenocarcinoma). Tenderness in the sternoclavicular joint, acne, periodontitis, and palmoplantar pustulosis were evident, and SAPHO syndrome was diagnosed. SAPHO syndrome is a rare disorder that results in synovitis, acne, pustulosis, hyperostosis, and osteomyelitis. Bone scintigraphy showed tracer accumulation in the costal cartilage, sternoclavicular joint, and cervical vertebrae 6-7. Although the bone lesions of SAPHO syndrome were difficult to differentiate from bone metastasis of pulmonary adenocarcinoma, metastatic bone tumors were ruled out by magnetic resonance imaging, computed tomography, and fluorodeoxyglucose positron emission tomography. There have been no previously reported cases of lung cancer with comorbid SAPHO syndrome. We report such a case and discuss the relevant literature, particularly that concerned with the evaluation of bone lesions.     

Síndrome SAPHO en la infancia. Presentación de un caso clínico

The acronym of SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) combines a cluster of cutaneous and musculoskeletal manifestations, such as hyperostosis of bones of the anterior chest wall associated with acne fulminans and hidradenitis suppurativa. There are no validated diagnostic criteria in children. Nonsteroidal anti-inflammatory drugs are not always sufficient, and the use of corticosteroids, disease-modifying agents, tumor necrosis factor-α inhibitors or bisphosphonates may be necessary.We present the case of a child with polyarticular involvement, osteoarthritis of the sternoclavicular joint with severe inflammatory disorders and acne conglobata, with an excellent response to intravenous pamidronate.     

An infrequent presentation of SAPHO syndrome

We describe a case of SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) with an unusual presentation in a 14 year-old girl with low grade fever which lasts 8 months, left low back pain and elevated erythrocyte sedimentation rates and protein C-reactive with chronic anaemia. A radiograhy of the lower limbs showed a lytic image with osteitis and hyperostose in the right fibula, as a casual finding. This information, in addition to the acne, pustulosis, sternoclavicular arthritis and the studies got from the magnetic resonance image (MR) of spine, pointed out the diagnosis of SAPHO.     

Intravenous pamidronate in the treatment of sternoclavicular hyperostosis

The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare clinical entity in which osteosclerosis and osteolysis are consistent radiological findings. We present a patient with SAPHO syndrome manifesting as painful sternoclavicular hyperostosis treated successfully with pamidronate. For the first time, a reduction in isotope bone scan activity was documented in parallel to a favourable clinical response. Bisphosphonates have potent antiosteoclastic and anti-inflammatory effects. By virtue of their dual effects on bone remodelling and inflammation, they seem an appropriate therapy in the management of SAPHO syndrome. This case demonstrates the efficacy of pamidronate, both clinically and radiologically, as first line therapy for patients with isolated hyperostosis.     

Tuberculosis of the sternoclavicular joint

Tuberculosis is seen in every part of the body, but sternoclavicular joint tuberculosis is rare. We report a case of tuberculosis of the sternoclavicular joint in 70-year-old woman having complained of the right sternoclavicular joint swelling. She had a previous history of pulmonary tuberculosis, and visited her doctor for right sternoclavicular joint swelling on February 2006. A chest CT scan showed a low density area with destructive osseous changes in the right sternoclavicular joint. Definite diagnosis could not be done by twice needle biopsy, but we diagnosed her as tuberculosis of the sternoclavicular joint based on the clinical course and the findings of the examination. As her condition did not improve after 3 months treatment with anti-tuberculous drugs, we conducted therapeutic surgical procedure. Definite diagnosis of sternoclavicular joint tuberculosis was made on the basis of the presence of mycobacteria in the histological specimen and PCR-TB positive result. We kept the wound opened and continued administration of anti-tuberculous drugs, and her condition does not deteriorate. Tuberculosis should be considered in case of a patient with arthritis and previous history of tuberculosis, even if it is seen in rare location. Diagnostic and therapeutic surgical procedure should be taken into consideration, if there is no improvement of the condition after a diagnosis of bone and joint tuberculosis, and the administration of chemotherapy for tuberculosis.     

Psoriatic arthritis, nail disease and pustules following Hodgkin's lymphoma

SIR, We refer to the association of pustules with arthritisboth in the well-defined SAPHO (synovitis, acne, pustulosis,hyperostosis and osteitis) syndrome [1] and in relation to theevidence of an increased prevalence of arthritis in acne [2].In the SAPHO syndrome, acne may evolve to guttate psoriasis[1]. The close association and overlap of psoriatic arthritiswith the SAPHO syndrome is well recognized [3, 4]. A 37-yr-old Caucasian woman presented in August 1998 with a3-yr history of pain and swelling of her right hand and feet.She     

Chronic sternal osteomyelitis complicating primary manubriosternal septic arthritis

We present a 40-year-old woman complaining of worsening chest pain. She was previously treated with a prolonged course of antibiotics for suspected sternal osteomyelitis. Radiological investigations were suggestive of ongoing inflammation within the manubriosternal joint. Formal surgical debridement yielded evidence corroborating the diagnosis although microbiological samples were negative. Prolonged empirical treatment with intravenous antibiotics leads to a complete resolution of symptoms. Primary culture-negative manubriosternal septic arthritis is rare, and suboptimal treatment, particularly if confused with other conditions such as synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome, compounds its considerable morbidity.     

SAPHO syndrome treated with pamidronate: an open-label study of 10 patients

BACKGROUND: In recent years the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) has been encountered more frequently. However, clinical evidence indicating superiority of a specific therapeutic modality is still absent. Pamidronate, a second-generation bisphosphonate, has a pronounced effect on bone metabolism by suppressing bone resorption. We report our clinical experience with intravenous pamidronate in SAPHO syndrome. METHODS: Between the years 1999 and 2003 we treated 10 patients with the SAPHO syndrome who did not respond to NSAIDs, oral corticosteroids, colchicine, methotrexate, sulphasalazine or infliximab. All patients were treated with 60 mg pamidronate, given intravenously within an hour. In cases of no response a subsequent dose was given within a month and if there was a partial response an additional infusion was given after 4 months. The primary endpoint was the disappearance of recurrent bouts of bone pain, osteitis or hyperostosis, or recurrent synovitis. Reduction of the frequency of attacks by 50% was regarded as a partial response. RESULTS: Seven of the patients were females and three were males. The age at diagnosis ranged from 26 to 68 yr. All patients had axial or peripheral arthritis and cutaneous involvement; three had severe acne, eight had pustulosis and two had concomitant psoriasis vulgaris. Hyperostosis of the anterior chest wall involving either sternocostal or sternoclavicular joints, as seen on technetium 99 bone scintigraphy, was detected in all patients. Complete remission was observed following therapy in six patients, three others partially responded and only one patient had no response. Two patients needed four cycles of pamidronate infusion, one patient needed three, six needed two infusions and one patient remitted following a single pamidronate infusion. In all but one patient pamidronate was effective in preventing recurrent bouts of pustulosis. CONCLUSION: Pamidronate seems to be a very effective mode of therapy for patients with the SAPHO syndrome, by promoting remission in all components of the disorder, such as bone, joint and skin involvement, and ceases the bouts that characterize this disorder.     

Diagnosing the SAPHO syndrome: a report of three cases and review of literature

SAPHO, an acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, is a heterogeneous entity with myriad presentations and features overlapping with other entities. It is a differential in patients presenting with skin and bone symptoms, either singly or in combination. Often misdiagnosed radiologically as a malignancy or infection, the diagnosis is seldom thought of. We present three cases referred to us for evaluation of findings unrelated to the presenting symptoms. After evaluation, a ⁹⁹Tc bone scan was ordered, which showed the ‘bull’s head sign’ in all the three cases, confirming the diagnosis. We review the literature for SAPHO. It has a few features which point to its diagnosis and can help us to distinguish it from other seronegative arthritis. The clinician should be aware of this entity and should not hesitate to order a ⁹⁹Tc bone scan. We conclude that SAPHO is not rare, but rather, it is underdiagnosed. High index of suspicion is necessary for diagnosis. A ⁹⁹Tc bone scan is diagnostic and should be ordered in patients having any of the presenting features of the syndrome. We put forward the suggestion of using ⁹⁹Tc bone scintigraphy to define a ‘pre-MRI’ stage of ankylosing spondylitis.     

SAPHO: rare or just not recognized?

OBJECTIVE: The SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome describes an association between musculoskeletal disorders, in particular hyperostosis involving the bones and joints of the anterior chest wall, and various dermatologic conditions. It has been reported in Europe and Japan, but no Australian series have been published. We describe the clinical, laboratory, and radiographic features of a group of patients with the SAPHO syndrome and compare this with the literature. METHODS: We performed a retrospective review of patients seen in our department between 1990 and 1998 who met the proposed diagnostic criteria for SAPHO. Information regarding age, sex, disease duration, skeletal site(s) of disease, presence of skin disease, previous treatment, and response to treatment was collected. Laboratory tests were reviewed, as was all available radiology and bone scintigraphy. RESULTS: Six women with a mean age of 40 years fulfilled the criteria for SAPHO. The skeletal manifestations were similar to those reported in the literature, with hyperostosis of the anterior chest wall being the central feature. Cervical spine and pubic bone were other sites of involvement, whereas sacroiliitis and peripheral joint synovitis were not seen. Skin disease was less frequent in our population than has been reported in other series. Nonsteroidal anti-inflammatory drugs were frequently prescribed as first-line treatment but had limited efficacy. Intravenous pamidronate was administered to two patients, resulting in complete resolution of pain in one patient and 50% reduction in pain in the other. CONCLUSIONS: The SAPHO syndrome may be underrecognized as the skin manifestations in our patients were mild or absent. Although optimal treatment for these patients remains unclear, it is important to make the diagnosis of SAPHO to avoid unnecessary investigations and treatment.     

In SAPHO syndrome anti-TNF-alpha therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations

OBJECTIVES: SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare disease combining skin, bone and joint manifestations. In recent years new therapeutic strategies have been tried, among them TNF-alpha-blocking agents. We report our experience with infliximab in four cases of SAPHO syndrome refractory to conventional therapies. METHODS: Between 2002 and 2005, four cases of SAPHO syndrome (two females and two males; mean age 49.7 yr) responding poorly to conventional drugs were treated with infliximab. The dose was 5 mg/kg, according to the protocol used in spondyloarthropathies, with infusions at 0, 2 and 6 weeks followed by 6 weeks intervals. No active cutaneous manifestations were present at the time of starting therapy. RESULTS: Complete remission of osteoarticular involvement was achieved after the second or third infusion, and the positive response was maintained for up to 12 months. A patient relapsed after discontinuation of infliximab, because of infectious complication. Palmoplantaris pustulosis relapsed in two patients after three and six infusions, respectively; there was slight improvement after discontinuation of anti-TNF-alpha drugs. CONCLUSIONS: Infliximab seems to be a very effective therapy for osteoarticular complaints of SAPHO syndrome. Cutaneous involvement responded less favourably, palmoplantaris pustulosis relapse being a possible complication.     

Two cases of SAPHO syndrome accompanied by classic features of Behcet’s disease and review of the literature

We describe two patients with SAPHO (synovitis–acne–pustulosis–hyperostosis–ostitis) syndrome who presented some of the classic features of Behcet’s disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet’s disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet’s disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.     

The SAPHO syndrome: a clinical and imaging study

The purpose of this study is to describe the clinical and radiological manifestations of patients with the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Retrospective study (1984–2007) was performed in a single center. All patients with the SAPHO syndrome were included. Fifty-two patients were included: 26 male, mean age at diagnosis is 42±12 years. Ostearticular involvement was present before cutaneous involvement in 59.6% of patients and concomitantly in 23.5%. Anterior chest pain was the commonest clinical manifestation, it was present in 38 patients (73%), followed by peripheral arthritis in 17 patients (32%), and sacroliliac pain in 14 patients (26.9%). Cutaneous involvement was present in 33 patients (63.5%). HLA B27 antigen was present in eight patients (17.7%). Bone scintigraphy showed an increased uptake in 42 patients (93.3%). The location of the uptake was mainly in sternoclavicular and manubriosternal joints. CT scan was performed in all “hot joints” showing sclerosis, erosions, hyperostosis, and soft tissue involvement. Refractory patients were treated mainly with pamidronate. Although SAPHO syndrome is an entity that share features that fit into a variety of established disease categories, the present study has a homogenous clinical and radiological pattern that gives support to believe that the SAPHO syndrome is an isolated clinical entity.     

Successful treatment of SAPHO syndrome with adalimumab: a case report

SAPHO syndrome is a disorder involving the skin, bone and joints. The underlying causes of SAPHO are poorly understood, and treatment is, therefore, directed towards the individual symptoms. However, many patients are refractory to treatment, and new treatment options are needed. Herein, we describe a 28-year-old patient with SAPHO syndrome and palmoplantar pustulosis seen at our hospital. Treatment was initiated with non-steroidal anti-inflammatory drugs, but clinical improvement was poor. The addition of sulfasalazine and oral alendronate also failed to alleviate symptoms. We subsequently commenced treatment with adalimumab 40 mg every 15 days and suspended bisphosphonates. Following 4 weeks’ treatment with adalimumab, there was clear articular improvement and disappearance of palmoplantar pustulous lesions. Nocturnal inflammatory lumbar pain and global disease assessment were also improved. To our knowledge, this is the first report on the use of adalimumab for SAPHO. More studies are required to confirm our findings.     

Skeletal changes during the course of pustulosis palmoplantaris--report of two cases

We report two cases of coincidence palmoplantar pustulosis and joint changes. Two patients fulfilled criteria for arthroosteitis pustulosa: pustular eruptions of the palms and soles and pain of sterno-clavicular joint. They also fulfills criteria for SAPHO syndrome: osteoarticular manifestations of palmoplantar pustulosis. Clinical examination and scintigraphy confirmed the diagnoses. Treatment was started with antibiotics and nonsteroid anti-inflammatory drugs. Oral corticosteroids therapy with methotrexate was given to one patient.     

A case of SAPHO syndrome with destructive spondylodiscitis suspicious of tuberculous spondylitis

We report a rare case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in which the differential diagnosis included tuberculous spondylitis and the patient ultimately required reconstructive spinal surgery. The patient was a 60-year-old woman who presented with severe low-back and leg pain after treatment for tuberculosis. Roentgenography and magnetic resonance imaging of the lumbar spine revealed destructive changes suggestive of tuberculous spondylitis. [¹⁸F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography showed uptake in the cervical spines, lumbar spines, and sacroiliac joints from which she was suspected of having SAPHO syndrome without skin manifestations. However, as her symptoms did not respond to conservative treatment, we performed reconstructive surgery of the lumbar spine. Spinal specimens obtained surgically showed nonspecific inflammation and fibrous hypertrophy of the bone marrow, confirming a diagnosis of the SAPHO syndrome. Her symptoms improved markedly after surgery, although she required occasional prednisolone for moderate polyarthralgia and leg pain.