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Niemann-Pick disease is an inherited lipid storage disorder caused by the deficiency of acid sphingomyelinase, which results in accumulation of sphingomyelin within cells of several organs and consequent tissue damage. The broad clinical spectrum of this disorder may overlap with that of systemic lupus erythematosus, hindering differential diagnosis. Herein, we report the case of a patient affected by Niemann-Pick type B disease intertwined with clinical and serological features of systemic lupus erythematosus. Two novel mutations in the SMPD1 gene were found in compound heterozygosity: p.A36V and IVS2 + 8 T > G., (© The Author(s) 2015.)

To assess whether the immune derangement previously observed in SAPHO syndrome could be linked to variations in blood TH1, TH2 or TH17 lymphocytes frequency. Seven SAPHO patients with a protracted course of the disease were studied ex-vivo for intracellular cytokines production by means of flow-cytometry and compared with matched groups of Psoriatic Arthritis patients and healthy controls. The Kruskal-Wallis test on the median of the three categories showed that there is a significant association between the TH17 levels and the category (p value = 0.02474). The mean and variance for the proportion of IL-17 producing CD4+ cells were compared between groups showing significant differences between SAPHO versus PsA subgroup (p = 0.05) and SAPHO versus healthy controls (p = 0.008). Interestingly, activation of TH17 axis, but not of TH1 and TH2, has been found, and can be observed both in patients with different activity of the disease or treated with different drugs. The TH17 increase in peripheral blood of our SAPHO subjects resembles the one recently found in patients with different AIDs. Novel therapeutic options in these patients may therefore include IL-17 blockade.

Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is a rare and often unrecognized disease with prominent inflammatory cutaneous and articular manifestations. Since the identification of the syndrome many immunosuppressive drugs have been used for the management of SAPHO, with variable results. The use of anti- TNF-α agents as a therapeutic option for SAPHO cases unresponsive or refractory to conventional drugs, demonstrated their efficacy for bone, skin and joints manifestations. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 β , IL-6 and IL-8, involved in inflammation, acute-phase response induction and chemotaxis. IL-1 inhibition strategies with Anakinra have proven their efficacy as first and second line treatment. We herein review the literature concerning the use of biological drugs in patients with SAPHO syndrome. In addition, we describe for the first time the use of Ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and Anakinra. This anti-IL12/IL23 agent could be a promising therapeutic option, also considering the opportunity to interfere with the IL23/TH17 pathway, which we recently found disturbed. Furthermore, a rationale emerges for the use of the new anti-IL-1 antagonists or the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.

Refractory or recurrent infections of skin, nails, and the mucous membranes are clinical signs of chronic mucocutaneous candidiasis, frequently associated with immunological defects. Here we describe a 39-years-old female patient, with familial CMC, that presented with an extensive infection caused by an azole-resistant Candida albicans isolate, successfully treated with posaconazole.