**6.6 SAPHO syndrome and CMRO**

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome and CMRO (chronic recurrent multifocal osteomyelitis) represent pathologic entities related to Psoriasis and PPP in regard to the relationship between infection and autoimmunity. In genetically susceptible individuals, environmental factors (mainly infections) play a critical role in the pathogenesis of autoimmune diseases. Molecular similarity of microbial and host antigens has recently been proposed as a promoting factor for pathogen expansion when microbial agents are not recognized as alien and not completely eliminated (Rozin, 2009).

SAPHO syndrome is now recognized as a distinct medical entity: a reactive infectious osteitis. Infectious agents isolated from SAPHO patients have gained special attention for many years. Their possible etiological role is supported by the pathogen isolation from different sites: anterior chest wall, spine, synovial fluid, bone tissue and skin pustules. A range of pathogens have been found, including Staphylococcus aureus, Hemophilus parainfluenzae, Actinomyces, and even Treponema pallidum (Arnson, 2008). Propionibacterium acnes is a much more frequent pathogen and plays a particular role. Multiple affected members who segregated a SAPHO syndrome-like phenotype had neutrophil dysfunction and reduced internal oxydant production (Ferguson & al., 2008). That may explain the inability of the innate system to eliminate the pathogen from

Head and Neck Psoriasis 101

Standardized incidence ratios (SIR) was found to be 2.80 (95% CI 1.96, 3.87) for oral cavity and pharynx cancer in a nationwide series of psoriasis patients from Sweden with a hospital discharge diagnosis of psoriasis made during 1965–83, who were alive and free from malignancy 1 year after first discharge, compared with the national population (Boffetta & al., 2001). Psoriasis was associated with a significantly increased prevalence ratio of lip, oral cavity and pharynx cancer (1.49; [1.22, 1.80]), in a national database in

Psoriasis is a disease treated near exclusively from dermatologists. Nevertheless some factors indicate the need for a new attention by the head and neck area specialists, especially

Recent literature focuses on relationship between autoimmunity and infection, the latter representing the prince environmental factor that could play a critical role in the pathogenesis of autoimmune diseases in susceptible individuals with the production of cross-reacting antibodies and the induction of the inflammatory second hit. When infectious agents are not recognized as alien and not completely eliminated, pathogen expansion

As above mentioned important relationship has been demonstrated between tonsillar T cells

Further investigations with translation from bench research to clinical knowledge and vice versa and with interrelation between dermatologists and head and neck specialists could result in considerable progress in understanding immunopathogenesis of Psoriasis and

Akagi, A. ; Tajima, S. ; Ishibashi, A. ; Yamaguchi, N. & Nagai, Y. (1999). Expression of type

Al Robaee, A.A. (2010). Molecular genetics of Psoriasis (Principles, technology, gene

Ammar, M. ;Zaraa, I. ; Bouchleka Souissi, C. ; Dhaoui, A. ; Doss, N. ; Ben Osman, A. ; El

Arnson, Y. ; Rubibow, A. ; Amital, H. (2008). Secondary syphilis presenting as SAPHO

Bhatia, A. ; Singh, B. ; Amarji, B. ; Negi, P. ; Shukla, A. & Katare, O.P.(2011). Novel stain-free

Behnam, S.M. ; Behnam, S.E. & Koo, J.Y. (2005). Smoking and Psoriasis, *Skinmed.,*4(3):174-6. Bloor, B.K. ; Tidman, N ; Leigh, I.M. ; Odell, E. ; Dogan, B. ; Wollina, U. ; Ghali, L. &

XVI collagen in human skin fibroblasts: enhanced expression in fibrotic skin

location, genetic polymorphism and gene expression), *Int J Health Sci (Qassim)*

Gaied, A. & Mokni, M. (2009). Familial Psoriasis : descriptive report of 9 families, *La* 

lecithinized coal tar formulation for Psoriasis, *Int J Dermatol*, 15. doi: 10.1111/j.1365-

Waseem, A. (2003). Expression of keratin K2e in cutaneous and oral lesions:

could be promoted by molecular similarity of microbial and host antigens.

and skin lesion in PPP patients with immune response to α-streptococci.

by the otorhinolaringologists and maxillofacial surgeons.

diseases, *J Invest Dermatol*, 113:246–250.

*tunisie Medicale*, 87 (011 ): 750-754.

4632.2011.04913.x. [Epub ahead of print]

syndrome features. *Clin Exp Rheumatol*, 26:1119-1121.

Taiwan (Tsai & al. 2011).

other immuno-mediated diseases.

4(2):103-27.

**9. References** 

**8. Conclusion** 

affected sites and justifies long-term or permanent antibiotic therapy (Rozin, 2009; Magrey, 2009). Treatment of SAPHO syndrome remains empirical as the underlying aetiopathogenesis is unclear.

A growing body of literature has identified the association between neutrophilic dermatoses and multifocal, aseptic bone lesions in children, termed chronic recurrent multifocal osteomyelitis (CRMO). Classically, patients present with swelling, pain, and impaired mobility of the affected area, with skin lesions developing concurrently or in the future. Bone biopsy reveals inflammatory changes consistent with infectious osteomyelitis, but cultures and histologic staining invariably fail to identify an infectious source. Patients are refractory to antibiotic therapy, but dramatically respond to systemic steroids and may need to be maintained on low-dose steroids to prevent relapse. Numerous authors have suggested that CRMO and SAPHO syndrome lie along the same clinical spectrum (Tlougan, 2009; Shilling, 2000).

#### **7. Psoriasis and tumours in head and neck area**

Overexpression of S100A7 (psoriasin), a small calcium-binding protein, has been associated with the development of Psoriasis and carcinomas in different types of epithelia but its precise functions are still unknown. Using human tissue specimens, cultured cell lines and a mouse model it was found (Zhou & al., 2008) that S100A7 is highly expressed in preinvasive, well-differentiated and early staged human squamous cell carcinoma of the oral cavity (SCCOC), but little or no expression was found in poorly differentiated, laterstaged invasive tumors. Interestingly those researchers showed that S100A7 inhibits both SCCOC cell proliferation in vitro and tumor growth/invasion in vivo. Furthermore, they demonstrated that S100A7 is associated with the beta-catenin complex, and inhibits betacatenin signaling by targeting beta-catenin degradation via a non canonical mechanism that is independent of GSK3beta-mediated phosphorylation. More importantly their studies also indicated that beta-catenin signaling negatively regulates S100A7 expression. Thus, this reciprocal negative regulation between S100A7 and beta-catenin signaling implies their important roles in tumor development and progression. Despite its high levels of expression in early stage of SCCOC tumorigenesis, S100A7 actually inhibits SCCOC tumor growth/invasion as well as tumor progression. Downregulation of S100A7 in later stages of tumorigenesis increases beta-catenin signaling, leading to promotion of tumor growth and tumor progression.

Significantly increased risk of cancer was demonstrated in patients with Psoriasis at an average of 9.3 years after discharge from hospital. This risk, amounting to 1.4 times that in the general population, is mainly relative to skin and lung cancer in both sexes and to pharynx and larynx cancer in men. Still this data are not definitive as no studies have been published with bias correction for smoke and alcohol consumption. Non-melanoma skin cancer is the most common malignancy, occurring in 196 of 795 patients with cancer: standardized incidence ratio 2.4 for men and 2.6 for women. This means an overall lifetime risk (up to the age of 75 years) of 14.1%. Women run the highest risk of basal cell carcinoma in the age range 20-40 years, while men in the age range 30-60 years run a particularly high risk of squamous cell carcinoma (Frentz & Olsen, 1999).

affected sites and justifies long-term or permanent antibiotic therapy (Rozin, 2009; Magrey, 2009). Treatment of SAPHO syndrome remains empirical as the underlying

A growing body of literature has identified the association between neutrophilic dermatoses and multifocal, aseptic bone lesions in children, termed chronic recurrent multifocal osteomyelitis (CRMO). Classically, patients present with swelling, pain, and impaired mobility of the affected area, with skin lesions developing concurrently or in the future. Bone biopsy reveals inflammatory changes consistent with infectious osteomyelitis, but cultures and histologic staining invariably fail to identify an infectious source. Patients are refractory to antibiotic therapy, but dramatically respond to systemic steroids and may need to be maintained on low-dose steroids to prevent relapse. Numerous authors have suggested that CRMO and SAPHO syndrome lie along the same clinical spectrum (Tlougan,

Overexpression of S100A7 (psoriasin), a small calcium-binding protein, has been associated with the development of Psoriasis and carcinomas in different types of epithelia but its precise functions are still unknown. Using human tissue specimens, cultured cell lines and a mouse model it was found (Zhou & al., 2008) that S100A7 is highly expressed in preinvasive, well-differentiated and early staged human squamous cell carcinoma of the oral cavity (SCCOC), but little or no expression was found in poorly differentiated, laterstaged invasive tumors. Interestingly those researchers showed that S100A7 inhibits both SCCOC cell proliferation in vitro and tumor growth/invasion in vivo. Furthermore, they demonstrated that S100A7 is associated with the beta-catenin complex, and inhibits betacatenin signaling by targeting beta-catenin degradation via a non canonical mechanism that is independent of GSK3beta-mediated phosphorylation. More importantly their studies also indicated that beta-catenin signaling negatively regulates S100A7 expression. Thus, this reciprocal negative regulation between S100A7 and beta-catenin signaling implies their important roles in tumor development and progression. Despite its high levels of expression in early stage of SCCOC tumorigenesis, S100A7 actually inhibits SCCOC tumor growth/invasion as well as tumor progression. Downregulation of S100A7 in later stages of tumorigenesis increases beta-catenin signaling, leading to promotion of tumor growth and

Significantly increased risk of cancer was demonstrated in patients with Psoriasis at an average of 9.3 years after discharge from hospital. This risk, amounting to 1.4 times that in the general population, is mainly relative to skin and lung cancer in both sexes and to pharynx and larynx cancer in men. Still this data are not definitive as no studies have been published with bias correction for smoke and alcohol consumption. Non-melanoma skin cancer is the most common malignancy, occurring in 196 of 795 patients with cancer: standardized incidence ratio 2.4 for men and 2.6 for women. This means an overall lifetime risk (up to the age of 75 years) of 14.1%. Women run the highest risk of basal cell carcinoma in the age range 20-40 years, while men in the age range 30-60 years run a particularly high

aetiopathogenesis is unclear.

2009; Shilling, 2000).

tumor progression.

**7. Psoriasis and tumours in head and neck area** 

risk of squamous cell carcinoma (Frentz & Olsen, 1999).

Standardized incidence ratios (SIR) was found to be 2.80 (95% CI 1.96, 3.87) for oral cavity and pharynx cancer in a nationwide series of psoriasis patients from Sweden with a hospital discharge diagnosis of psoriasis made during 1965–83, who were alive and free from malignancy 1 year after first discharge, compared with the national population (Boffetta & al., 2001). Psoriasis was associated with a significantly increased prevalence ratio of lip, oral cavity and pharynx cancer (1.49; [1.22, 1.80]), in a national database in Taiwan (Tsai & al. 2011).
