CANDLE syndrome (
hronic
typical
eutrophilic
ermatosis with
ipodystrophy and
levated temperature) is a rare, genetic autoinflammatory disease due to abnormal functioning of the multicatalytic system ...proteasome-immunoproteasome. Several recessive mutations in different protein subunits of this system, located in one single subunit (monogenic, homozygous, or compound heterozygous) or in two different ones (digenic and compound heterozygous), cause variable defects in catalytic activity of the proteasome-immunoproteasome. The final result is a sustained production of type 1 interferons (IFNs) that can be very much increased by banal triggers such as cold, stress, or viral infections. Patients start very early in infancy with recurrent or even daily fevers, characteristic skin lesions, wasting, and a typical fat loss, all conferring the patients a unique and unmistakable phenotype. So far, no treatment has been effective for the treatment of CANDLE syndrome; the JAK inhibitor baricitinib seems to be partially helpful. In this article, a review in depth all the pathophysiological, clinical, and laboratory features of CANDLE syndrome is provided.
...testing such as imaging (computed tomography scan, magnetic resonance imaging, ultrasound), lab tests, genetic testing, or immunopathology are often deemed necessary to define the extent, ...activity, outcome and heredity of skin diseases, but are seldom indispensable for a diagnosis in our day-to-day clinical practice. ...these tools can be used to establish the malignant potential and select molecular targets for skin tumours (e.g., diagnosis and therapy of melanoma), or characterize the genomic and proteomic expression of rare and common genetic dermatoses, among many other potential applications. Sharing our clinical experience, our observations as well as clinical photographs of our most challenging cases (always with the patients' consent and respect for their privacy), are crucial aspects of our medical duties and commitments to improve the quality of care.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
3.
Welcome to the JEADV Clinical Practice Torrelo, Antonio
JEADV clinical practice,
March 2022, 2022-03-00, 20220301, 2022-03-01, Volume:
1, Issue:
1
Journal Article
Peer reviewed
Open access
Clinicians practising Dermatology and Venereology are eager for high-quality and intuitive visual material that is helpful for their daily practice, but this is nowadays hard to find in classic ...printed journals. ...new channels are necessary for publishing the unceasingly increasing amount of information coming from the scientific community of Dermatology and Venereology. Mostly educational and practical content provides practical, easy-to-access, relevant and up-to-date information for the daily practice of dermatology with an aim to help promote the best patient care. Furthermore, our innovative Patient Page will feature reliable and understandable health information for patients and topics focusing on doctor–patient relations and the difficulties of living with skin diseases.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible proteasome subunit β5i, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis ...with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production.
An infant with SAM-like syndrome (severe dermatitis, allergies, and metabolic wasting) was found to have a substantial increase in the number of T-helper 17 cells. Administration of the monoclonal ...antibody secukinumab produced remarkable improvement, with symptom relief and restoration of normal growth.
Background
European roundtable meeting recommendations on bathing and cleansing of infants were published in 2009; a second meeting was held to update and expand these recommendations in light of new ...evidence and the continued need to address uncertainty surrounding this aspect of routine care.
Methods
The previous roundtable recommendations concerning infant cleansing, bathing, and use of liquid cleansers were critically reviewed and updated and the quality of evidence was evaluated using the Grading of Recommendation Assessment, Development and Evaluation system. New recommendations were developed to provide guidance on diaper care and the use of emollients. A series of recommendations was formulated to characterize the attributes of ideal liquid cleansers, wipes, and emollients.
Results
Newborn bathing can be performed without harming the infant, provided basic safety procedures are followed. Water alone or appropriately designed liquid cleansers can be used during bathing without impairing the skin maturation process. The diaper area should be kept clean and dry; from birth, the diaper area may be gently cleansed with cotton balls/squares and water or by using appropriately designed wipes. Appropriately formulated emollients can be used to maintain and enhance skin barrier function. Appropriately formulated baby oils can be applied for physiologic (transitory) skin dryness and in small quantities to the bath. Baby products that are left on should be formulated to buffer and maintain babies’ skin surface at approximately pH 5.5, and the formulations and their constituent ingredients should have undergone an extensive program of safety testing. Formulations should be effectively preserved; products containing harsh surfactants, such as sodium lauryl sulfate, should be avoided.
Conclusion
Health care professionals can use these recommendations as the basis of their advice to parents.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults.
We report integrated baricitinib safety data in patients ...with up to 3.9-years exposure.
Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg-4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated.
2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported.
In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD.
NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7)
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction: Impetigo is the most common bacterial skin infection in children. Treatment is becoming complicated due to the development of antimicrobial resistance, especially in the main pathogen, ...Staphylococcus aureus. Ozenoxacin, a novel non-fluorinated topical quinolone antimicrobial, has demonstrated efficacy in impetigo.
Areas covered: This article reviews the microbiology, pharmacodynamic and pharmacokinetic properties of ozenoxacin, and its clinical and microbiological efficacy in impetigo.
Expert opinion: In an environment of increasing antimicrobial resistance and concurrent slowdown in antimicrobial development, the introduction of a new agent is a major event. Ozenoxacin is characterized by simultaneous affinity for DNA gyrase and topoisomerase IV, appears to be impervious to certain efflux pumps that confer bacterial resistance to other quinolones, shows low selection of resistant mutants, and has a mutant prevention concentration below its concentration in skin. These mechanisms protect ozenoxacin against development of resistance, while the absence of a fluorine atom in its structure confers a better safety profile versus fluoroquinolones. In vitro studies have demonstrated high potency of ozenoxacin against staphylococci and streptococci including resistant strains of S. aureus. Clinical trials of ozenoxacin in patients with impetigo reported high clinical and microbiological success rates. Preserving the activity and availability of ozenoxacin through antimicrobial stewardship is paramount.
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