Treatment with subcutaneous canakinumab once every 8 weeks was associated with a rapid remission of symptoms in most patients with CAPS. (ClinicalTrials.gov number, NCT00465985.)

SummaryA broad range of skin diseases occurs in patients with ESRD: from the benign and asymptomatic to the physically disabling and life-threatening. Many of them negatively impact on quality of life. Their early recognition and treatment are essential in reducing morbidity and mortality. The cutaneous manifestations can be divided into two main categories: nonspecific and specific. The nonspecific manifestations are commonly seen and include skin color changes, xerosis, half-and-half nails, and pruritus. The specific disorders include acquired perforating dermatosis, bullous dermatoses, metastatic calcification, and nephrogenic systemic fibrosis. This review article describes these conditions and considers the underlying pathophysiology, clinical presentations, diagnosis, and treatment options.

The investigation of interleukin 1β (IL-1β) in human inflammatory diseases is hampered by the fact that it is virtually undetectable in human plasma. We demonstrate that by administering the anti–human IL-1β antibody canakinumab (ACZ885) to humans, the resulting formation of IL-1β–antibody complexes allowed the detection of in vivo–produced IL-1β. A two-compartment mathematical model was generated that predicted a constitutive production rate of 6 ng/d IL-1β in healthy subjects. In contrast, patients with cryopyrin-associated periodic syndromes (CAPS), a rare monogenetic disease driven by uncontrolled caspase-1 activity and IL-1 production, produced a mean of 31 ng/d. Treatment with canakinumab not only induced long-lasting complete clinical response but also reduced the production rate of IL-1β to normal levels within 8 wk of treatment, suggesting that IL-1β production in these patients was mainly IL-1β driven. The model further indicated that IL-1β is the only cytokine driving disease severity and duration of response to canakinumab. A correction for natural IL-1 antagonists was not required to fit the data. Together, the study allowed new insights into the production and regulation of IL-1β in man. It also indicated that CAPS is entirely mediated by IL-1β and that canakinumab treatment restores physiological IL-1β production.

NCT00685373 (clinicaltrials.gov).

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Cryopyrin-associated periodic syndrome (CAPS) is a rare hereditary inflammatory disorder encompassing a continuum of three phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease. Distinguishing features include cutaneous, neurological, ophthalmologic, and rheumatologic manifestations. CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes. Defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS. Diagnosis is often delayed and requires a thorough review of clinical symptoms. Remarkable advances in our understanding of the genetics and the molecular pathway that is responsible for the clinical phenotype of CAPS has led to the development of effective treatments. It also has become clear that the NLRP3 inflammasome plays a critical role in innate immune defense and therefore has wider implications for other inflammatory disease states.

Background: Hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) are both rare inflammatory skin conditions that are associated with systemic inflammatory diseases. We performed a retrospective medical chart review of patients with an overlap of HS and PG.Observations: We identified 11 cases of PG lesions presenting in patients with HS. Ten of the patients were women, and 9 were obese. All the patients developed HS lesions first, a median of 2.5 years (range, 0-15 years) preceding the appearance of PG lesions. All patients required multiple therapeutic agents because their diseases were often poorly responsive to standard therapies. Two patients received tumor necrosis factor inhibitors;