An impressive number of microorganisms live inside and on healthy humans. The normal gastrointestinal tract alone contains 10 ¹⁴ bacteria, which is 100 times the number of cells in the body. The microorganisms are essential for normal regulation of the immune system and induction of tolerance. At the same time, immune defence against potential pathogens is needed. It is not surprising that the delicate balance between tolerance and immune response can be compromised and can lead to pathology. This volume deals with some examples where proven or suspected microbial interactions lead to disease. The recent discovery that Porphyromonas gingivalis possesses citrullinating enzymes similar to those in human cells makes them suspect as aetiologic agents in rheumatoid arthritis (RA) We may be at the beginning of better understanding of a number of disorders, where infectious agents could contribute to the aetiology. This volume contains examples of such conditions.

In medical school some 50 years ago, students were told that joint cavities are extremely sensitive to infection compared with other parts of the body, which is not the case. In fact, normal joints are provided with strong innate defence mechanisms, explaining why septic arthritis is relatively rare. However, when occurring, it requires prompt recognition and action. As pointed out in the chapter by Martin-Mola et al., the incidence is increasing, and mortality is not trivial. Increasing age and use of immunosuppressive agents are contributing to this. The Spanish authors also stress the age differences and the higher risk among the elderly and children.

The chapter on the Chikungunya virus describes the increasing global occurrence of this arbovirus-induced condition whose name means “That which is bent up.” The prominent arthralgias of the initial acute phase result in a characteristic stooped position. Large outbreaks of the disease described from Africa around 1950 are now also seen in Asia, and imported cases occur in Europe, notably in epidemic form in Italy. Global warming may favour spread of the infection. The chronic phase has intriguing similarities with RA. Macrophages with living virus have been identified in joint fluid, and genetic susceptibility factors seem to be involved. A number of research agenda are addressing these findings, which may have bearing on this and other joint diseases triggered by a microbial agents, perhaps even for RA. The increasing prevalence of Chikungunya disease clearly calls for high awareness of the condition among practicing physicians.

In Finland, many of the seminal discoveries regarding reactive arthritis originated from the classical thesis by Paronen et al. It is interesting to read the comprehensive review on reactive arthritis by Timo Hanno, which points out the substantial prevalence of prolonged or persisting musculoskeletal symptoms in patients after acute episodes of reactive arthritis , although he points out the lack of follow-up studies of Chlamydia -triggered arthritis. The lack of evidence for the efficacy of antibiotic therapy in non- Chlamydia -triggered reactive arthritis is also emphasised. For reasons that are not entirely clear, the prevalence of Yersinia as trigger for arthritis is said to have diminished dramatically in Finland, and similar trends are seen in other countries . One explanation may be better hygiene in slaughterhouses.

The term ‘ Chlamydia -induced reactive arthritis’ can be a misnomer, as viable organisms can be present intra-articularly. A more neutral name would be Chlamydia -triggered arthritis. In their chapter, Drs. Carter and Inman point out that this well-established entity is often overlooked and that it definitely should not be regarded as a rare condition. Indeed, the incidence may be similar to that of RA. Molecular differences between acute infection and persistent disease and reactive arthritis begin to become identified. Thus, heat shock protein-60 (HSP-60) expression is suggested to play an important role in chronicity by preventing apoptosis of infected cells. Another recent finding is linking ocular and not only genital serovars of Chlamydia to arthritis. An interesting observation made in experimental Chlamydia disease was that susceptibility to reactive arthritis correlated with low initial expression of pro-inflammatory cytokines. One is reminded of the old clinical observation in, for example, Yersinia -triggered arthritis that arthritis patients typically had only minor gastroenteric symptoms. Although no RCT has been performed, anecdotal evidence indicates that treatment with tumour necrosis factor-α (TNF-α)-inhibitors ameliorates the condition. The putative role of antibiotics in the treatment is still not answered, but the authors cite evidence of positive results of prolonged therapy in a subset of chronic post-Chlamydia arthritis patients, which probably distinguishes these patients from those with post-enteric reactive arthritis.

As the title of the SAPHO chapter indicates, microbial involvement is still not finally proven although highly likely. Drs Assman and Simon give an initiated presentation of the still partly controversial spectrum of the SAPHO and SAPHO-like conditions. The unusual geographic distribution remains enigmatic, although compatible with an environmental agent. Identification of genetic abnormalities in two conditions, the Majeed and the PAPA syndrome with features reminiscent of SAPHO, raise suspicion of such factors in this condition. Proprionibacterium acnes still emerges as a possible aetiological agent based on repeated independent reports cited in the review. Clearly, further clinical and basic research needs to be performed.

Gulen Hatremi and Hasan Yazici, the superexperts working on Behςet’s syndrome, review the current worldwide epidemiology showing high, intermediate and virtual absence in different populations. The extended search for a microbial aetiology is still ongoing; the main suspects are herpes simplex virus (HSV) and streptococci. The thorough review of the management shows the need for differential therapies according to clinical manifestations. Immunosuppressive agents outweigh antithrombotic and antimicrobial intervention.

Francesca Nacci and Marco Matucci Cerinic contribute a comprehensive review of a decade’s experience with infections in patients treated with TNF-α inhibitors. They highlight the overwhelming evidence for modest increase in the prevalence of serious infection in all populations. The risk of activation of latent tuberculosis is of particular importance, and it is higher with the monoclonal anti-TNF agents. Pre-treatment screening for latent tuberculosis has been hampered by the low specificity and sensitivity of the tuberculine test, especially in patients with RA . Therefore, the recent developments in testing for latent tuberculosis are of particular interest . Nacci and Matucci Cerinic also review risks in patients with viral disease, where limited evidence show no or perhaps even positive influence of anti-TNF-α therapy.