Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy And Elevated Temperature Syndrome Research Articles

Annular Neutrophilic Dermatoses.

Neutrophilic dermatoses (NDs) are a group of diseases characterized by sterile neutrophilic infiltrations. Many of the NDs usually present with infiltrated erythematous plaques, nodules, urticarial plaques, or pustules. Lesions may show variability, and atypical presentations may develop among the NDs. Annular lesions have been reported in many NDs and may lead to diagnostic problems. Clinical features and histopathologic findings such as localization of the neutrophilic infiltrate, existence of other cell types, and absence of true vasculitis may be helpful to distinguish NDs. Some of these NDs are associated with infections, inflammatory diseases, and malignancies. In most NDs, systemic steroids and dapsone are very effective and usually first choices. Colchicine, antimicrobials, such as doxycycline, tetracycline, and sulphapyridine, and other immunosuppressants, such a cyclosporine, methotrexate, and mycophenolate mofetil have been used successfully in treating many NDs. TNF-α inhibitors have also been used successfully in many NDs. JAK kinase inhibitors are effective in CANDLE syndrome, anakinra in neutrophilic urticarial dermatosis, and intravenous immunoglobulin in resistant pyoderma gangrenosum. We discuss the diagnosis and management of the NDs that may present with annular lesions.

Rare health conditions 39: Krabbe disease; chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (‘CANDLE’); Batten disease; and working with young children

The purpose of this series is to highlight a range of rare health conditions: those that affect no more and usually fewer than 1 person in every 2000. Many healthcare assistants (HCAs) and nurses will encounter some of these conditions, given the high number of these conditions. This 39th article will briefly explore three of these conditions—Krabbe disease, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE), and Batten disease—and also discuss working with young children and their families.

Insights into CANDLE Syndrome

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a recently described chronic autoinflammatory disease, pathophysiologically related to intracellular proteasome/immunoproteasome dysfunction. This review chronicles the recognition of CANDLE syndrome, the developments in the understanding of the pathomechanism, genetic background, and the emerging therapeutic strategies of this condition.

CANDLE syndrome

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is an autoinflammatory disease firstly reported in 2010, which is characterized by periodic fever, early onset, weight-height growth retardation, recurrent violaceous annular plaques on the trunk and extremities, eyelid swelling, lip hypertrophy, lipodystrophy, abdominal bulge, hepatomegaly and increased acute-phase reactants. Histopathological examination of skin lesions shows compact infiltration of atypical myeloid mononuclear cells mixed with mature neutrophils, eosinophils, lymphocytes and histocytes in the dermis, and sometimes in the subcutaneous adipose tissues. Immunohistochemical study reveals positive staining for CD68, LEDER and myeloperoxidase. CANDLE syndrome is a kind of proteasome-associated monogenic inherited disease, and more and more mutation sites have been reported to be related to its occurrence and development. There is no specific treatment for CANDLE syndrome, the quality of life of patients is severely affected, and the prognosis is poor in most patients. Glucocorticoids, immunosuppressive agents and biological agents may be effective for CANDLE syndrome in some patients. Key words: Hereditary autoinflammatory diseases; Skin manifestations; Diagnosis; Treatment outcome; Syndrome, CANDLE

Histologic and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous, and often annular cutaneous eruption. Although the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 patients with CANDLE syndrome by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils, and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathological and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder and further insight into the pathogenesis of this severe life-threatening condition.

PReS-FINAL-2202: A novel PSMB8 mutation associated with CANDLE syndrome

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly described autoinflammatory disease, which had been recently reported in 9 patients. It is characterized by onset during the first year of life of recurrent fevers, purpuric skin lesions, arthralgia, progressive lipodystrophy, hypochromic or normocytic anemia, delayed physical development and increased levels of acute phase reactants.

Comparative cytokine analysis across a spectrum of genetically and/or clinically defined auto-inflammatory syndromes

Background/purposeAuto-inflammatory diseases constitute a group of disorders that manifest systemic inflammation in the absence of infection, auto-antibodies or auto-reactive T cells. A specific genetic mutation is identified in some of...