T<sub>H</sub>17 cells are increased in the peripheral blood of patients with SAPHO syndrome

Firinu, Davide; Barca, Maria Pina; Lorrai, Maria Maddalena; Perra, Silvia; Cabras, Stefano; Muggianu, Emma; Martino, Maria Luisa; Manconi, Paolo Emilio; Giacco, S.R. Del

doi:10.3109/08916934.2014.906582

Cited by 58 publications

(50 citation statements)

References 31 publications

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“…In addition, an upregulation of IL‐8, IL‐17, IL‐18, TNF‐α and IL‐1 have been shown . We did not find evidence of elevated serum cytokines (IL‐1β, IL‐6, IL‐8, IL‐12, interferon‐γ, TNF‐α and soluble IL‐2 receptor α) in our patient, but these investigations were done during treatment and no baseline levels were performed.…”

Section: Discussionmentioning

confidence: 51%

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Successful treatment of SAPHO syndrome with apremilast

Adamo¹,

Nilsson²,

Krebs³

et al. 2018

Br J Dermatol

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SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare disease with inflammatory osteoarticular and skin involvement. The pathogenesis of SAPHO syndrome remains unclear, but evidence suggests it may be an autoinflammatory disease triggered upon exposure to infectious agents in genetically predisposed individuals. Induction of the interleukin (IL)-23/T helper 17 axis in addition to neutrophil activation seem to play a key role, and therapies targeting these immunological pathways, including tumour necrosis factor (TNF) inhibitors, ustekinumab, secukinumab and the IL-1 inhibitor anakinra, are potential treatment options that need further investigation. Here we report a case of a 24-year-old woman with SAPHO syndrome who presented at our clinic with palmoplantar pustulosis and sternoclavicular joint involvement. Previous treatments with topical steroids and keratolytics combined with nonsteroidal anti-inflammatory drugs, intravenous methylprednisolone, methotrexate and sulfasalazine had all failed to improve symptoms. Therapy with etanercept was not tolerated, and because of a previous demyelinating peripheral neuropathy, further treatment with TNF inhibitors was avoided. We initiated ustekinumab 45 mg, which improved skin manifestations but not joint pain. Dose escalation to 90 mg initially improved joint pain, but the dose had to be reduced to 45 mg again because of increased infections. During subsequent 45-mg ustekinumab treatment, joint pain exacerbated so we switched to adalimumab which caused an exacerbation of the disease, so we switched to secukinumab, which improved skin and joint symptoms significantly but was associated with a pustular hypersensitivity reaction. Finally, we began treatment with apremilast, a pan-cytokine approach, resulting in stabilization of the skin and joint symptoms without side-effects. To our knowledge, this is the first case report of apremilast as a treatment for SAPHO syndrome.

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Section: Discussionmentioning

confidence: 51%

“…IL‐17 is a cytokine produced by Th17 cells, which have been shown to be increased in patients with SAPHO syndrome . As secukinumab had to be discontinued in our patient because of a hypersensitivity reaction with a positive lymphocyte transformation test, we introduced a treatment with apremilast.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of SAPHO syndrome with apremilast

Adamo¹,

Nilsson²,

Krebs³

et al. 2018

Br J Dermatol

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“…Increasing evidence points to P2X7R as a main player in Th17 differentiation and IL‐17 secretion . In line with these findings, Th17 cells were recently found to be increased in the peripheral blood of patients with SAPHO …”

Section: Synovitis Acne Pustulosis Hyperostosis and Osteitismentioning

confidence: 55%

“…62 In line with these findings, Th17 cells were recently found to be increased in the peripheral blood of patients with SAPHO. 63 The hereditary basis of SAPHO has been supported by the finding of familial clustering cases, 64 but no specific mutations have been found in patients with SAPHO. PSTPIP2, which is involved in macrophage activation, neutrophil motility and osteoclast differentiation, has recently been supposed to play a role in innate immunity and development of autoinflammatory bone disorders, including SAPHO syndrome.…”

Section: Synovitis Acne Pustulosis Hyperostosis and Osteitismentioning

confidence: 99%

Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation

et al. 2016

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Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1β to its active isoform IL-1β. The overproduction of IL-1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.

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“…Another study demonstrated that by altering the composition of the intestinal microbiome with dietary manipulations, it was possible to modify the expression of sterile osteomyelitis phenotype [15]. Furthermore, recent human immunologic studies have identified increased Th17 cells in the peripheral blood of SAPHO patients [16], reduced IL-10 production by stimulated monocytes from CRMO patients [17], and increased expression of the inflammasome-related genes, IL1B , CAS1 , and ASC , in PBMC from CRMO patients [18]. …”

Section: Chronic Recurrent Multifocal Osteomyelitis and Autoinflammatmentioning

confidence: 99%

Advances in the genetically complex autoinflammatory diseases

Ombrello

2015

Semin Immunopathol

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Monogenic diseases usually demonstrate Mendelian inheritance and are caused by highly penetrant genetic variants of a single gene. In contrast, genetically-complex diseases arise from a combination of multiple genetic and environmental factors. The concept of autoinflammation originally emerged from the identification of individual, activating lesions of the innate immune system as the molecular basis of the hereditary periodic fever syndromes. In addition to these rare, monogenic forms of autoinflammation, genetically-complex autoinflammatory diseases like the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), Behçet’s disease, and systemic arthritis also fulfill the definition of autoinflammatory diseases - namely the development of apparently unprovoked episodes of inflammation without identifiable exogenous triggers and in the absence of autoimmunity. Interestingly, investigations of these genetically-complex autoinflammatory diseases have implicated both innate and adaptive immune abnormalities, blurring the line between autoinflammation and autoimmunity. This reinforces the paradigm of concerted innate and adaptive immune dysfunction leading to genetically-complex autoinflammatory phenotypes.

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T_H17 cells are increased in the peripheral blood of patients with SAPHO syndrome

Cited by 58 publications

References 31 publications

Successful treatment of SAPHO syndrome with apremilast

Successful treatment of SAPHO syndrome with apremilast

Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation

Advances in the genetically complex autoinflammatory diseases

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TH17 cells are increased in the peripheral blood of patients with SAPHO syndrome

Cited by 58 publications

References 31 publications

Successful treatment of SAPHO syndrome with apremilast

Successful treatment of SAPHO syndrome with apremilast

Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation

Advances in the genetically complex autoinflammatory diseases

Contact Info

Product

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T_H17 cells are increased in the peripheral blood of patients with SAPHO syndrome