Anders Vahlquist – Excerpta from Volume 96 of ActaDV
Fig. 4. Endoplasmic reticulum( ER) stress-centred working model of rosacea pathogenesis. Upregulated ER stress via transcription factor 4( ATF4) and S1P activates p38 mitogen-activated protein kinase( p38 MAPK) that phosphorylates and activates CCAAT / enhancer-binding protein-α( C / EBPα). C / EBPα increases the expression of cutaneous antimicrobial peptides( CAMP) and osteopontin( OSN) stimulating inflammation, angiogenesis, fibrosis and granuloma formation. S1P induces skin hypersensitivity and causes vasodilation and flushing. Toll-like receptor 2( TLR2) increases the activity of kallikrein 5( KLK5) enhancing the proteolytic cleavage of CAMP. Upregulation of TLR2 on peripheral neurones increases the susceptibility for pain. Bioactive peptide of CAMP( LL-37) activates caspase-1, the key enzyme of the NLRP3 inflammasome producing interleukin-1β( IL-1β), which activates Th17 cells.( Text modified from ref 15; with permission from Acta Derm Venereol). therapies which inhibit the stress mediators and down-regulate TLR in the skin. Another example of the current focus on skin inflammation is the paper by Steinhoff et al( 16), reviewing the pathoaetiology and treatment options in facial erythema of rosacea.
Sexually transmitted infections
Syphilis, once the biggest simulator in Medicine, is becoming increasingly common again but is still occasionally difficult to diagnose and treat, especially in immunosuppressed patients. In a study from Copenhagen, Salado-Rasmussen et al.( 17) investigate the serological response to treatment with doxycycline compared with penicillin in 202 HIV-infected individuals. They conclude that doxycycline is a favourable option in this group of patients.
Another rare occurrence which should not be forgotten is disseminated goncococcal infection, typically presenting with fever, pustular skin lesions and joint involvement, and usually responding quickly to antibiotics. However, in a report from Gothenburg, Rehnström et al.( 18) describe two cases of gonococcal osteomyelitis resulting in permanent sequelae because of a delayed diagnosis and treatment( Fig. 5).
Lastly some comforting news about STI and concurrent treatment with biologicals. There has been suspicion that anogenital HPV infections might be enhanced by treatment with immunosuppressive drugs, including TNF-a inhibitors. If so this would be of special concern in psoriasis patients who have a higher incidence of anogenital HPV infections than, for example, patients with inflammatory bowel disease( IBD), who are also candidates for biologics. However, a study of Handisurya et al. from Austria( 19) now shows in 222 patients with psoriasis or IBD that there is no increased prevalence of anogenital HPV during treatment with TNF-inhibitors.
Fig. 5.( A) X-ray of the left knee joint showing reduction in height of the cartilage laterally and medially( arrows), fissures on the tibial articulate surface and general osteopaenia.( B) X-ray of the left hand showing that adjacent edges of the articulate surfaces in the 3 rd metacarpophalangeal joint( arrows) are irregular and sclerotic, corresponding to status post-septic arthritis.( From ref 18 with permission from Acta Derm Venereol).
References
1. Harwood C, Proby CM, Inman GJ, Leigh IM. The promise of genomics and the development of targeted therapies for cutaneous squamous cell carcinoma. Acta Derm Venereol 2016; 96: 3 – 16. 2. Ratour-Bigot C, Chemidling M, Montlahuc C, Abirached G,
Madjlessi N, Bullier C, et al. squamous cell carcinoma following
92 Info from the Editor of ActaDV
Forum for Nord Derm Ven 2016, Vol. 21, No. 4