Matteo Colina

Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: A single center study of a cohort of 71 subjects

OBJECTIVE To assess the basic features and outcomes of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS We identified all patients seen in our unit between 1990 and 2008 diagnosed according to the proposed inclusion criteria with SAPHO syndrome, who had a followup of at least 2 years. RESULTS Seventy-one patients (48 women, 23 men) with SAPHO syndrome were identified. The median disease duration at the end of followup was 10 years (interquartile range [IQR] 7-15 years), and the median followup duration was 11 years (IQR 6-11.5 years). Six patients were diagnosed with Crohns disease. Fourteen patients had never had cutaneous involvement, but 8 patients presented >1 skin manifestation. Nine patients (13%) presented a limited (<6 months) monophasic disease course, 25 cases (35%) had a relapsing-remitting course, and 37 patients (52%) had an acute painful phase with a prolonged course lasting >6 months. A total of 4% of the patients were HLA-B27 positive. Female sex (odds ratio [OR] 7.2, 95% confidence interval [95% CI] 2.2-22.9) and the presence at onset of anterior chest wall (ACW) involvement (OR 5.7, 95% CI 1.8-18.1), peripheral synovitis (P = 0.0036), skin involvement (OR 10.3, 95% CI 3.4-31.1), and high values of acute-phase reactants (OR 7.7, 95% CI 2.7-22) were correlated with a chronic disease course and involvement of new osteoarticular sites. CONCLUSION A chronic course is the more common evolution of SAPHO syndrome. Female sex, elevated erythrocyte sedimentation rate and C-reactive protein values, ACW involvement, peripheral synovitis, and skin involvement at the onset seem to be associated with a chronic course.

SAPHO syndrome and infections

The syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) encompasses a broad spectrum of cutaneous manifestations associated with osteitic and hyperostotic lesions, which typically may involve the anterior chest wall (ACW). The aetiopathogenetic mechanisms as well as the nosographic framing of the disease are still not fully defined although an important role has been suggested for Propionibacterium acnes (P. acnes). This germ might be able to stimulate both the innate and the T-cell-mediated immune system. The elicited immunological response could be an attempt to eliminate the germ thus inducing the perpetuation of the inflammation. Whether the osteo-articular changes seen in SAPHO could be attributable directly to the infection or to an inflammatory reaction induced by pathogenic material remains a debated issue. The current concept of SAPHO syndrome as a reactive infectious osteitis in genetic predisposed subjects seems appealing, but it has not been yet demonstrated.

Dysregulation of P2X7 receptor-inflammasome axis in SAPHO syndrome: successful treatment with anakinra

Francesca Barbieri, Massimiliano Parodi, Giuseppe Zampogna, Francesco Paparo and Marco A. Cimmino Dipartimento di Medicina Interna, Clinica Reumatologica and Dipartimento di Medicina Interna, Sezione di Diagnostica per Immagini, Università di Genova, Genova, Italy Accepted 12 February 2010 Correspondence to: Marco A. Cimmino, Dipartimento di Medicina Interna, Clinica Reumatologica, Università di Genova, Viale Benedetto XV, 6, 16132 Genova, Italy. E-mail: cimmino@unige.it

The Evolution of Adult-Onset Still Disease: An Observational and Comparative Study in a Cohort of 76 Italian Patients

OBJECTIVES Adult-onset Stills disease (AOSD) is a potentially crippling or life-threatening rare disease that may be self-limited, intermittent, and chronic. Clinical predictors of outcome are still lacking, as is information on the rate of progress of its chronic course. The main objective is to identify factors that improve our ability to predict the course of AOSD, and factors associated with the rate of progress of its chronic course. A comparison with the literature is included. METHODS A retrospective cohort observational study conducted at the tertiary-referral Rheumatology Unit in Ferrara, Italy. RESULTS Seventy-six patients (44 females and 32 males) referred to the Unit and who satisfied the criteria for AOSD were identified. Our findings on white AOSD patients are largely compatible with those previously published. Ferritin level, as well disease activity score (DAS(28)), is associated with the rate of progression of the articular manifestations of the disease. A polyarthritis persisting over 6 months is associated with the development of a chronic articular course, irrespective of the size of the involved joints. CONCLUSIONS Ferritin, being associated with the course of AOSD, could play a role in the diagnosis of the disease. Together with DAS(28), it might also serve as a useful predictor for the rate of progress of the chronic course of the disease, as measured with simple erosion narrowing score.

Combination treatment with etanercept and an intensive spa rehabilitation program in active ankylosing spondylitis.

The aim of this study is to determine the effects of a combination treatment with etanercept and spa rehabilitation versus etanercept alone on function, disability and quality of life in a group of patients with active ankylosing spondylitis (AS). Sixty patients with AS underwent etanercept as suggested by ASAS/EULAR recommendations. As the clinical and laboratory conditions improved, 30 patients accepted the proposal of coupling the medical therapy with a 7-day rehabilitation program in a thermal baths centre; the remaining 30 subjects continued to take the biologic agent alone. The comparisons between the 2 groups were made after 3 and 6 months. The primary outcome was an improvement in BASFI. The secondary outcome was an improvement in the visual analogic scale of EuroQol (EQ-5Dvas). After 6 months a statistically significant improvement in BASFI (p < 0.05) and EQ-5DVAS (p < 0.05) scores was observed in both groups. The mean change in EQ-5DVAS value showed a statistically significant difference in favour of the combination therapy group versus the monotherapy group (22 vs 32, p < 0.05). A therapeutic regimen combining etanercept with an intensive rehabilitation program contributes to disability reduction and ameliorates quality of life for AS patients.

Fatal myocarditis in adult-onset Still disease with diffuse intravascular coagulation

Adult-onset Still disease (AOSD) is a rare condition disease of unknown etiology, characterized by quotidian or double quotidian spiking fever, with an evanescent pink-salmon rash, arthritis and multi-organ involvement. Diagnosis is usually clinical and made after other diseases in the differential diagnosis are excluded. We herein report the case of a patient with a remarkable familial autoimmune background in whom adult Still disease started off with a diffuse intravascular coagulation, probably triggered by a macrophage activation syndrome, followed by an acute interstitial myocarditis, leading to a fatal complete atrioventricular block. This case highlights that AOSD represents a troubling condition and that it may suddenly get worse with life-threatening events.

Multicentric reticulohistiocytosis and fibroblastic rheumatism

Multicentric reticulohistiocytosis (MRH) and fibroblastic rheumatism (FR) are uncommon disorders with similar joint and skin manifestations. They are usually included among the non-Langerhans histiocytoses, but recent insights drive some criticism. The diagnosis is often challenging and must be confirmed by the histological typical features. If the skin manifestations are missing, the arthritic complaints may be confused with those of other rheumatic disorders. In these cases, only a careful clinical and radiological evaluation leads to the correct diagnosis. The natural course of the diseases may rapidly develop into disabling manifestations, making an aggressive treatment strongly recommendable. There is emerging evidence that anti-tumour necrosis factor-α agents and bisphosphonates are promising drugs for MRH, while a course of methotrexate and steroids seems to be the best option for FR. Finally, the clinician should be aware that in many cases MRH, but not FR, is associated with a large number of systemic manifestations and with malignancy. This eventuality must be accurately ruled out.

Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series

OBJECTIVE We report the use of nicotine-patch therapy on active mucocutaneous lesions of Behçets disease (BD). METHODS Five BD ex-smoker patients with refractory active mucocutaneous manifestations were treated with nicotine patches for 6 months. RESULTS Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of mucocutaneous lesions. Other manifestations of BD did not respond and new manifestations appeared during this treatment. One patient had no benefit from therapy but on restarting smoking it was promptly effective. CONCLUSIONS Mucocutaneous lesions associated with BD may be modulated by smoking. Both smoking and nicotine-replacement therapy may be efficacious not only on oral aphthae, but also on other mucocutaneous manifestations, whereas the efficacy in the treatment and prevention of other systemic manifestations of BD is not proven. At least in ex-smokers, nicotine in its pure form is well tolerated and its use could be justified in selected cases of BD with predominant and recurrent refractory mucocutaneous manifestations.

Clinical and Radiological Characteristics of SAPHO Syndrome

The peculiar bone involvement, represented by osteitis, is the common denominator of SAPHO syndrome. Hyperostosis and osteitis are chronic inflammatory reactions involving the cortical and trabecular bone respectively; both are characterised by increased sclerosis. Hyperostosis appears radiologically as chronic endosteal and periosteal thickening with narrowing of the medullary canal, but areas of ostelysis may also be present. Conversely, osteitis appears as increased osteosclerosis involving the trabecular infrastructure of cancellous bone. The occurrence of hyperostosis with little or no osteitis is not uncommon. SAPHO syndrome may have a prolonged course with phases of reacutization and remission; the long-term prognosis is usually fairly good, but sometimes a disabling course may occur. Our experience demonstrated that the majority of patients suffering from SAPHO syndrome experienced a chronic course, requiring continous treatment, whilst in a third of the cases the patients reported multiple remission and exacerbations of the disease with flares lasting till to 8 months. Only in a minority of cases the bone inflammation faded and never recurred. Female sex, peripheral arthritis, ACW involvement, the coexistence of more than one cutaneous symptoms, and high inflammatory indices are correlated with a chronic disease course and involvement of new osteoarticular sites.

Antibiotics may be useful in the treatment of SAPHO syndrome

Dear Editor, We have read with great interest the article by Takizawa et al. [1] recently published in Modern Rheumatology, on the efficacy of minocycline in a patient with SAPHO syndrome. We fully agree with Takizawa et al., both on the possibility that SAPHO syndrome presents with marked inflammation and on the serious differential diagnosis that a severe inflammation localised at the spine with a positive scintiscan may result. In the described case report, the authors had initially chosen for antibiotic therapy on the suspicion of septic discitis, but X-ray and computed tomography scan revealed hyperostotic changes and erosions in the right sterno-clavicular joints, with inflammation in the adjacent soft tissues. In fact, these abnormalities on radiography are the hallmark of SAPHO syndrome [2]. We also agree with the authors that when inflammation of the surrounding soft tissue is detected, a biopsy should be mandatory in order to exclude malignancy. With regards to the use of tetracyclines—and antibiotics in general—in patients suffering from SAPHO syndrome, it is worth recalling that SAPHO syndrome is probably a primitive reactive osteitis in genetically predisposed subjects and that not only Propionibacterium acnes but also Staphylococcus aureus have been isolated from osteoarticular lesions in the anterior chest wall (ACW), spine, pustules and synovial fluid and tissue [2–7]. A wide range of other pathogens has been found, including Hemophilus parainfluenzae, Actinomycetes and Treponema pallidum [8]. However, at the present time, data from the literature favours Propionibacterium acnes, although this microorganisms has only been found occasionally in bacterial cultures. It is possible that the use of other procedures, such as PCR, would provide reliable data on the real frequency of P. acnes in osteitic bone lesions of SAPHO syndrome, leading to a better understanding of the aetio-pathogenesis of this disease. A low-virulence infection by P. acnes is probably an important trigger in the aetio-pathogenesis of SAPHO syndrome, especially when the microorganisms have access to the bone, thereby initiating or stimulating a chronic inflammatory response concomitant with systemic symptoms. Moreover, P. acnes can activate the complement and induces production and secretion of interleukin (IL)-1, IL-8 and tumour necrosis factor-alpha (TNF-a) [9]. In 2007 we described a case of SAPHO patient in which we were able to isolate P. acnes from a bone biopsy. In that case we treated the osteo-articular complaints of the patients with doxycycline because the antibiogram revealed that this tetracycline would be efficient. Noteworthy is that skin lesions have continued to recur regardless of this therapy [10]. Conversely, there has been evidence that TNF-a blocking agents and that IL-1 receptor antagonist anakinra is effective in SAPHO syndrome [2, 11, 12], suggesting M. Colina Rheumatology Service, Section of Internal Medicine, Department of Medicine, Ospedale ‘‘Santa Maria della Scaletta’’, Via Montericco, 4, 40026 Imola, Bologna, Italy