The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), one of the autoinflammatory syndromes, is caused by mutations in the gene coding for mevalonate kinase (MVK). We conducted the current study to assess the genetic, laboratory, and clinical features as well as the complications and course of disease in patients with genetically confirmed HIDS. In addition, we studied the quality of life and course of life in a selection of patients. Follow-up data were obtained by a questionnaire sent to all physicians of patients in the International HIDS Database. In addition, we assessed the course of life and quality of life in Dutch patients aged >16 years using validated quality of life instruments. Data were obtained from 103 patients from 18 different countries. The median age of first attack was 6 months (range, 0-120 mo), with a median period of 9.9 years from onset of disease to diagnosis. The most frequent symptoms that accompanied attacks of fever were lymphadenopathy, abdominal pain, arthralgia, diarrhea, vomiting, skin lesions, and aphthous ulcers. Amyloidosis was a severe but infrequent complication (2.9%). The median serum IgD level was 400 U/mL. IgD levels were normal in 22% of patients. The 4 most prevalent mutations (V377I, I268T, H20P/N, P167L) accounted for 71.5% of mutations found. The frequency of attacks decreased with the patient's increasing age, although 50% of patients over the age of 20 years still had 6 or more attacks per year. Many drugs have been tried in HIDS. Some patients responded to high-dose prednisone (24.4% response). Anakinra and etanercept can also be effective (33.3% response). Quality of life was determined in a subgroup of patients (n = 28). Social functioning, general health perception, and vitality were significantly lower in patients with HIDS than in controls, as were autonomy and social development. In addition, HIDS had an adverse impact on educational achievements and employment status. In conclusion, HIDS is an early-onset disease that is accompanied by an array of inflammatory symptoms. Although the frequency of attacks decreases during the patient's life, many patients continue to have frequent attacks. HIDS impairs several aspects of quality of life.

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Anakinra proved to be effective in three patients with Schnitzler's syndrome. This treatment is preferable to thalidomide, which induced a complete remission in one of our patients, as it has fewer side effects.

On-demand treatment with anakinra in HIDS decreases the duration and severity of fever attacks. Because of the burden of daily injections and relatively long asymptomatic intervals of HIDS, all patients with HIDS preferred on-demand treatment.

MSU crystals act in synergy with LPS for the induction of enhanced release of IL1 beta. Increased cleavage of proIL1 beta by urate-activated caspase 1 is proposed as the underlying mechanism.

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Detecting recurrent laryngeal carcinoma after radiotherapy for a primary tumour can be difficult. Early detection however, is an important prognostic factor. Although a biopsy should be performed in case of clinical suspicion, repeated negative biopsies do not exclude the presence of viable tumour. The trauma caused by biopsies in irradiated tissue may initiate infection, further oedema and failure to heal. We investigated these problems and evaluated the current care and its usefulness. A survey of the current practice concerning diagnostic procedures for detecting recurrent laryngeal carcinoma after radiotherapy in the major institutions treating head and neck cancer in The Netherlands was performed by means of a questionnaire. Furthermore, we performed a comprehensive analysis of the extent and yield of diagnostic work-up in a cohort of patients clinically suspected of a recurrence, who had undergone direct laryngoscopy between 1986 and 1998 in our institution, with a follow-up of at least 6 months. In case of suspected recurrence, 94% of the departments use direct laryngoscopy under general anaesthesia with the taking of biopsies as a diagnostic technique. Imaging does not play an important role. In our department 207 laryngoscopies were evaluated in 131 patients. In 70 patients the first laryngoscopy was negative. Of these initial negative laryngoscopies, 22 (31%) turned out to be false negative within 6 months. Thirty-seven patients remained disease free. They underwent 65 unnecessary laryngoscopies to come to this conclusion. In the decision to perform direct laryngoscopy, the conventional work up leaves room for improvement. Too many unnecessary laryngoscopies are performed. New imaging techniques such as FDG-PET or new applications of CT or MRI may improve the yield of direct laryngoscopy.

Summary The hereditary periodic fever syndromes encompass a rare group of diseases that have lifelong recurrent episodes of inflammatory symptoms and an acute phase response in common. Clinical presentation can mimic that of lymphoproliferative disorders and patients often go undiagnosed for many years. These syndromes follow an autosomal inheritance pattern, and the major syndromes are linked to specific genes, most of which are involved in regulation of the innate immune response through pathways of apoptosis, nuclear factor κΒ activation and cytokine production. In others, the link between the protein involved and inflammation is less clear. The recurrent inflammation can lead to complications, such as renal impairment due to amyloidosis and vasculitis, visual impairment, hearing loss, and joint destruction, depending on the specific syndrome. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients.