The mechanism involved in the development of diabetic neuropathy is complex. Currently, it is thought that chemokines play an important role in this process. The aim of this study was to determine how the level of some chemokines from the CXC subfamily varies in diabetic neuropathy and how the chemokines affect nociceptive transmission. A single intraperitoneal (i.p.) injection of streptozotocin (STZ; 200 mg/kg) resulted in an increased plasma glucose. The development of allodynia and hyperalgesia was measured at day 7 after STZ administration. Using Antibody Array techniques, the increases in CXCL1 (KC), CXCL5 (LIX), CXCL9 (MIG), and CXCL12 (SDF-1) protein levels were detected in STZ-injected mice. No changes in CXCL11 (I-TAC) or CXCL13 (BLC) protein levels were observed. The single intrathecal (i.t.) administration of CXCL1, CXCL5, CXCL9, and CXCL12 (each in doses of 10, 100, and 500 ng/5 μL) shows their pronociceptive properties as measured 1, 4, and 24 hours after injection using the tail-flick, von Frey, and cold plate tests. These findings indicate that the chemokines CXCL1, CXCL5, CXCL9, and CXCL12 are important in nociceptive transmission and may play a role in the development of diabetic neuropathy.
Rosacea is a chronic inflammatory skin disorder of a not fully understood pathophysiology. Microbial factors, although not precisely characterized, are speculated to contribute to the development of the condition. The aim of the current review was to summarize the rosacea-associated alterations in the skin, blood, and gut microbiome, investigated using culture-independent, metagenomic techniques. A systematic review of the PubMed, Web of Science, and Scopus databases was performed, according to PRISMA (preferred reporting items for systematic review and meta-analyses) guidelines. Nine out of 185 papers were eligible for analysis. Skin microbiome was investigated in six studies, and in a total number of 115 rosacea patients. Blood microbiome was the subject of one piece of research, conducted in 10 patients with rosacea, and gut microbiome was studied in two papers, and in a total of 23 rosacea subjects. Although all of the studies showed significant alterations in the composition of the skin, blood, or gut microbiome in rosacea, the results were highly inconsistent, or even, in some cases, contradictory. Major limitations included the low number of participants, and different study populations (mainly Asians). Further studies are needed in order to reliably analyze the composition of microbiota in rosacea, and the potential application of microbiome modifications for the treatment of this dermatosis.
Alopecia areata (AA) is a cell-mediated autoimmune disease in which a cytotoxic T-cell response against hair follicles occurs. AA has been demonstrated to frequently co-exist with atopic dermatitis (AD), and the coincidence of atopy predisposes to a more severe course of the disease. To date, therapeutic options in AA, especially in the pediatric population, are mainly limited to corticosteroids, irritants, sensitizers, and immunosuppressive agents. Recently, innovative therapies have emerged, among which Janus kinase (JAK) inhibitors, effective in both AD and AA, appear to be the most promising. Here, a 14-year-old girl with alopecia universalis (AU) and mild AD is demonstrated, who was successfully treated with a selective JAK1 inhibitor, upadacitinib, which has been approved for the treatment of AD in adults and children aged 12 years and older. Resolution of eczema and complete hair regrowth was achieved after 3 months of therapy. Apart from transient mild leukopenia at weeks 4 and 8, no adverse events were noted. Data in the literature on the efficacy and safety of JAK inhibitors in the treatment of AA in the pediatric population is based on single case reports and case series. So far, topical tofacitinib and ruxolitinib, as well as systemic tofacitinib, ruxolitinib, and baricitinib have been used off-label in this indication in children. Upadacitinib is another effective treatment option with a good benefit–risk ratio for patients with AA, including cases coexisting with AD.
Eosinophilic annular erythema (EAE) is a rare condition with a chronic relapsing and remitting course, characterized by the presence of annular or polycyclic erythematous and plaque lesions and prominent tissue eosinophilia on histopathology. There is an ongoing discussion on whether EAE is a subset of Wells syndrome (eosinophilic cellulitis) or a separate entity. To date, few cases of EAE have been reported in the literature; of these, about 40 cases were in adults and fewer than ten cases were in children. Given the rarity of this condition, there are no clear recommendations for its management. Systemic corticosteroids and antimalarials are the most commonly used medications used to treat EAE, but many cases have been reported in the literature that are resistant to treatment with these medications. Here, we present a 65-year-old female with EAE refractory to numerous systemic therapies (corticosteroids, hydroxychloroquine, dapsone, doxycycline, methotrexate) who showed a good response to mepolizumab, a humanized monoclonal antibody that blocks interleukin-5. To the best of our knowledge, this is the first reported case of mepolizumab therapy in a patient with EAE. We also review other treatment strategies that have been used to manage this condition to date. Targeting cytokines crucial for the functioning of eosinophils may be a novel direction in the management of EAE, but prospective, double-blinded and placebo-controlled studies are needed to provide further evidence.