A retrospective study of bone scintigraphy in the follow-up of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: is it useful to repeat bone scintigraphy for disease assessment?

OBJECTIVES: To investigate the value of repeated bone scintigraphy in the follow-up of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to characterize the changing pattern of osteoarticular lesions revealed by bone scintigraphy. METHOD: Twenty-four patients with SAPHO syndrome who had repetitively undergone bone scintigraphy and tests of inflammatory markers (erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)) were included in this retrospective study. The change in accumulation number was recorded as the difference in the number of accumulation sites between consecutive bone scintigraphy. The visual analog scale (VAS) for pain and medications prescribed were also reviewed. The relationships of the change in accumulation number with medication prescribed and change in ESR or CRP were analyzed. RESULTS: Twenty-four and 23 patients had follow-up tests of ESR and CRP, from which 30 and 28 follow-up data were obtained, containing the corresponding changes in ESR and CRP, respectively. A decrease in total accumulation number observed by bone scintigraphy was rarely observed, while decreases in ESR, CRP, and VAS were predominant. The accumulation number had significantly increased over time (follow-up with ESR: r = 0.389, p = 0.034; follow-up with CRP: r = 0.438, p = 0.020), in accordance with an "imprinting" pattern, while the inflammatory markers and VAS for pain predominantly decreased. There was no significant association between the change in accumulation number (local/total) and the change in ESR or CRP values (p > 0.05) or medications used for SAPHO (p > 0.05). CONCLUSIONS: This retrospective cohort study of 24 SAPHO patients demonstrated an "imprinting" pattern on bone scintigraphy, without a correlation to the decrease in inflammatory markers, patient disease assessment, or treatment type. Thus, repeated bone scintigraphy did not contribute an additional clinical value for the follow-up of patients with SAPHO.Key Points• In a cohort of 24 SAPHO patients, repeated bone scintigraphy revealed a continuous increase in tracer accumulation number, indicating an "imprinting" pattern.• The change in tracer accumulation number, defined as the difference in the number of accumulation sites between consecutive bone scintigraphy measurements, was inconsistent with the change in ESR, CRP, or VAS for pain.• The medications prescribed for SAPHO did not seem to contribute to a decrease in accumulation number.• Repeated bone scintigraphy did not seem to be useful for the assessment of disease activity in patients with SAPHO.

Enhanced migration and adhesion of peripheral blood neutrophils from SAPHO patients revealed by RNA-Seq.

BACKGROUND: SAPHO syndrome is a rare disease characterized by inflammatory lesions on skin and bones. Diversified manifestation and inadequate understanding of etiology has limited its diagnosis and treatment. The co-occurrence of other immune-mediated diseases strongly suggests an involvement of autoimmunity in SAPHO syndrome. However, the role of the largest population of circulating immune cells, neutrophils, is still not well explored. In this study, we performed RNA sequencing to profile the mRNA expression of neutrophils purified from peripheral blood of SAPHO patients to identify key genes associated with SAPHO syndrome, trying to find new functional molecules or biomarkers for this rare disease. RESULTS: A total of 442 differentially expressed genes were identified (p < 0.05, fold change > 2), in which 294 genes were upregulated and 148 genes were downregulated. Five differentially expressed genes of interest were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), among which S100A12 was upregulated and positively related to high-sensitivity C-reactive protein (hsCRP), while the downregulated gene MYADM was positively related to osteocalcin. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes were enriched in "systemic lupus erythematosus" and "ECM-receptor interaction". Gene ontology (GO) enrichment showed that differentially expressed genes may participate in biological processes such as "cell migration" and "cell adhesion". CONCLUSIONS: In conclusion, this study provides a first insight into transcriptome characteristics of SAPHO syndrome, indicating an over-active neutrophil recruitment in patients and possibly suggesting molecular candidates for further study on diagnosis and pathology of this disease.

Depression in patients with SAPHO syndrome and its relationship with brain activity and connectivity.

BACKGROUND: Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disease and there is no related literature concerning psychiatric symptoms in SAPHO patients. Thus, we believe that this will be the first paper to explore the episode and the neurobiological basis of depression symptoms in SAPHO patients using resting state functional magnetic resonance imaging (rs-fMRI). Twenty-eight SAPHO patients and fifteen age- and gender- matched normal controls (NC) were consecutively submitted to psychiatric evaluation and rs-fMRI scanning. RESULTS: 46.2% (13/28) of SAPHO patients were diagnosed as depression. The local spontaneous activity study showed that depressed SAPHO (D-SAPHO) patients had decreased amplitude of low-frequency fluctuation (ALFF) in the bilateral ventrolateral prefrontal cortex (VLPFC, attributed to the anatomical structures of Brodmann's area 47, 45 and 44) and right dorsolateral prefrontal cortex (DLPFC, attributed to the anatomical structures of Brodmann's area 8, 9 and 46), increased ALFF in the bilateral middle temporal gyrus, when compared to non-depressed SAPHO (ND-SAPHO) patients. The functional connectivity (FC) study disclosed that D-SAPHO patients had an increased FC in the anterior portions of default mode network (DMN) (the bilateral inferior frontal cortex, anterior cingulate cortex and insula cortex), and a decreased FC in the posterior areas of DMN (left middle occipital cortex), when compared to ND-SAPHO patients. Furthermore, correlation analysis revealed that both ALFF and FC values were significantly correlated with depression scores of SAPHO patients. CONCLUSION: These results prompt us to understand the underlying pathophysiological mechanism of depression in SAPHO syndrome, and demonstrate that abnormal brain functional areas may serve as effective biological indicators to monitor depression in the future.

The salivary proteome profile in patients affected by SAPHO syndrome characterized by a top-down RP-HPLC-ESI-MS platform.

SAPHO syndrome is a rare and often unrecognized disease with prominent inflammatory cutaneous and articular symptoms characterized by musculoskeletal manifestations (synovitis, hyperostosis, osteomyelitis) associated with dermatological conditions (severe acne and pustulosis). The acidic soluble fraction of whole saliva from 10 adult women affected by SAPHO syndrome and from a group of 28 healthy women was analysed by RP-HPLC-ESI-MS with the aim of discovering salivary biomarkers of the disorder. The levels of the oral proteins and peptides were correlated with clinical data. The following proteins showed a significant decreased concentration in saliva of SAPHO subjects with respect to controls: cystatin S1 and SN, histatins, the major acidic PRPs, P-C and P-B peptides. The cystatin SN abundance lowered according to the disease duration and histatins showed positive correlations with the C reactive protein. Statistical analysis performed excluding one patient with a different pattern of salivary proteins/peptides highlighted a positive relationship between cystatin S1, histatins 3, histatin 5, and the neutrophil count. Moreover, histatin 3 correlated positively with the total white cell count and negatively with the erythrocyte sedimentation rate. Levels and frequency of S100A12 protein showed a trend to increase in SAPHO patients. The high expression of this pro-inflammatory protein is probably related to the inflammatory response and to the altered neutrophil responses to functional stimuli that characterize SAPHO syndrome suggesting a possible application as a salivary biomarker.

Increased neutrophil infiltration, IL-1 production and a SAPHO syndrome-like phenotype in PSTPIP2-deficient mice.

OBJECTIVE: Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is involved in macrophage activation, neutrophil motility and osteoclast differentiation. However, the role of PSTPIP2 in inflammation and autoinflammatory diseases is still not clear. In this study, we generated PSTPIP2 knockout (Pstpip2(-/-)) mice to investigate its phenotype and role in autoinflammatory diseases. METHODS: We constructed a Pstpip2-targeting vector and generated Pstpip2(-/-) mice. The phenotype and immunopathology of Pstpip2(-/-) mice were analysed. RESULTS: All Pstpip2(-/-) mice developed paw swelling, synovitis, hyperostosis and osteitis, resembling SAPHO syndrome, an inflammatory disorder of the bone, skin and joints. Multifocal osteomyelitis was found in inflamed paws, with increased macrophage and marked neutrophil infiltrations in the bone, joint and skin. Profound osteolytic lesions with markedly decreased bone volume density developed in paws and limbs. Neutrophil-attracting chemokines and IL-1ß were markedly elevated in inflamed tissues. CONCLUSION: Our study suggests that PSTPIP2 could play a role in innate immunity and development of autoinflammatory bone disorders, and may be associated with the pathogenesis of human SAPHO syndrome.

Single-nucleotide polymorphisms p53 G72C and Mdm2 T309G in patients with psoriasis, psoriatic arthritis, and SAPHO syndrome.

Psoriasis (Ps), psoriatic arthritis (PsA), and SAPHO syndrome are diseases of unknown etiology that share common clinical features; however, family studies support the hypothesis of a genetic background for each of these diseases. To study the two common single-nucleotide polymorphisms (SNP) in the murine-double-minute-2-(Mdm2) and p53 genes in patients with Ps, PsA, and SAPHO syndrome. Genomic DNA was obtained from 187 patients with Ps, 50 with PsA, and 36 with SAPHO as well as 478 healthy controls. Mdm2-gene SNP T309G and p53-gene SNP G72C genotypes were determined by the polymerase chain reaction. Genotype and allele frequencies were analyzed with chi(2)-tests. Among the patients with Ps and PsA, no differences in allele or genotype frequencies of the p53-gene SNP G72C and Mdm2-gene SNP T309G were detected. However, in the SAPHO patients group, the frequencies of the Mdm2 SNP309 G allele and the genotype SNP 309 GG were significantly increased compared with the controls (G allele: 51.4 vs. 38.7%, P = 0.034; genotype GG: 36.1 vs. 14.2%, P = 0.002). In addition, the frequencies of the p53 SNP72 C allele and the genotype SNP 72 CC were also increased in the SAPHO patients cohort (C allele: 36.1 vs. 25.6%, P = 0.05; genotype CC: 16.7 vs. 6.3%, P = 0.05). SAPHO syndrome may be linked to an imbalance between MDM2 and p53 regulation with a "weak" p53-response associated with the Mdm2 SNP 309 G allele. In contrast, the p53 network does not seem to play a major role in pathogenesis of Ps or PsA.

Paciente con tumefacción en la articulación esternoclavicular. Síndrome SAPHO / Patient with numbness in the sternoclavicular joint: SAPHO Syndrome

El síndrome SAPHO está constituido por la asociación de alteraciones musculoesqueléticas y alteraciones dermatológicas. Presentamos el caso de un varón de 35 años que cumple criterios de síndrome SAPHO. Aunque el tratamiento de estos pacientes aún no está claro, es importante hacer el diagnóstico del síndrome SAPHO para realizar las investigaciones necesarias e instaurar el tratamiento. El término es un acrónimo de las manifestaciones más frecuentes: sinovitis, acné, pustulosis palmo-plantar, hiperostosis y osteítis (AU)

The SAPHO syndrome describes an association between musculoskeletal disorders and various dermatological conditions. We report the case of a 35-years-old man who fulfilled the criteria for SAPHO. Although the optimal treatment for these patients remains unclear, it is important to make the diagnosis of SAPHO to avoid unnecessary investigations and treatment. SAPHO is an acronym of the combination of synovitis, acne, pustulosis, hyperostosis, and osteitis (AU)