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Journal of the European Academy of... Mar 2022Germline autosomal dominant and autosomal recessive mutations in PERP, encoding p53 effector related to PMP-22 (PERP), a component of epidermal desmosomes, have been... (Review)
Review
BACKGROUND
Germline autosomal dominant and autosomal recessive mutations in PERP, encoding p53 effector related to PMP-22 (PERP), a component of epidermal desmosomes, have been associated with a spectrum of keratodermas. Monoallelic nonsense mutations cause Olmsted syndrome with severe periorificial keratoderma and palmoplantar keratoderma (PPK). Biallelic recessive frameshift and missense mutations are associated with milder forms of the disease, including generalised erythrokeratoderma and PPK.
OBJECTIVES
To add new insights into the genotype-phenotype correlations as a consequence of PERP mutations and to provide a comprehensive review of the literature.
METHODS
Among 26 previously unresolved families within a cohort of 180 extended Iranian families with syndromic or non-syndromic ichthyosis, two families with shared clinical features were examined by whole-exome sequencing and genome-wide homozygosity mapping. Mycological and dermatopathological studies were performed to further characterise their atypical phenotypic presentations.
RESULTS
In two unrelated multiplex consanguineous families affected by ichthyosis, two novel biallelic PERP variants, NM_022121.5, c.89T > C, p.Leu30Pro and c.466G > C, p.Gly156Arg, located inside of genomic homozygosity regions of the probands were detected. Interestingly, some patients had areas of scaly psoriasiform plaques on the background of generalised ichthyosis that appeared during active cutaneous fungal infections. Mycological examinations of these lesions revealed infections caused by Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Histopathology of the psoriasiform lesions shared some features with psoriasis, which when combined with clinical presentation, led to incorrect diagnosis of guttate psoriasis or pustular psoriasis.
CONCLUSIONS
PERP variants in ichthyosis patients can confer susceptibility to recalcitrant cutaneous fungal infections. Additionally, patients with episodic psoriasiform dermatitis in the setting of keratoderma should be considered for PERP genotyping and cutaneous fungal examinations.
Topics: Eczema; Genes, Tumor Suppressor; Humans; Ichthyosis; Iran; Membrane Proteins; Mutation; Mycoses; Pedigree
PubMed: 34863005
DOI: 10.1111/jdv.17856 -
Dermatology (Basel, Switzerland) 2023Dupilumab is the first approved IL-4Rα inhibitor for the treatment of atopic dermatitis at present with good efficacy and safety. However, there have been several... (Review)
Review
BACKGROUND
Dupilumab is the first approved IL-4Rα inhibitor for the treatment of atopic dermatitis at present with good efficacy and safety. However, there have been several reports of psoriasis and psoriasiform manifestations occurring after dupilumab therapy in recent years, showing a new paradoxical cutaneous reaction associated with biologics.
SUMMARY
This is a scoping review in order to summarize the demographics and epidemiology, clinical manifestations, diagnosis, potential pathogenesis, and promising management of dupilumab-associated psoriasis and psoriasiform manifestations.
Topics: Humans; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Psoriasis; Interleukin-4; Interleukin Inhibitors; Treatment Outcome
PubMed: 37100035
DOI: 10.1159/000530608 -
BMJ Case Reports Mar 2019
Topics: Acquired Immunodeficiency Syndrome; Administration, Cutaneous; Anti-Retroviral Agents; Arm; Dermatitis; Glucocorticoids; Humans; Immunocompromised Host; Leg Dermatoses; Male; Middle Aged; Psoriasis; Torso
PubMed: 30850572
DOI: 10.1136/bcr-2018-228690 -
The Annals of Pharmacotherapy Apr 2024
PubMed: 38590149
DOI: 10.1177/10600280241244511 -
Dermatologic Therapy Nov 2022
Topics: Humans; Eczema; Antibodies, Monoclonal, Humanized; Heterocyclic Compounds, 3-Ring; Treatment Outcome
PubMed: 36001502
DOI: 10.1111/dth.15788 -
The Journal of Dermatology Jun 2022
Topics: Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Crohn Disease; Eczema; Female; Gastrointestinal Agents; Humans
PubMed: 35199379
DOI: 10.1111/1346-8138.16318 -
Cutis Nov 2022
Topics: Humans; RNA, Messenger; COVID-19; Eczema; mRNA Vaccines
PubMed: 36638370
DOI: 10.12788/cutis.0656 -
Pediatric Dermatology Nov 2021Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform...
BACKGROUND/OBJECTIVES
Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform eruptions after initiation of dupilumab in children.
METHODS
Records of patients ≤18 years of age with atopic dermatitis who developed psoriasiform dermatitis during treatment with dupilumab were reviewed retrospectively.
RESULTS
Six children, 4-18 years of age, on dupilumab for severe atopic dermatitis developed new-onset psoriasiform dermatitis at a median duration of 8 months (range, 6-12 months) after dupilumab initiation. Typical locations of psoriasis were involved (face, scalp, trunk, and extensor extremities). The majority showed clearance or near clearance with the use of medium-strength to potent topical corticosteroid ointments and 83% continued use of the dupilumab. A 7th patient had psoriasis, in addition to severe atopic dermatitis, and the psoriasis was unmasked by its failure to respond to dupilumab.
CONCLUSION
Although unusual, psoriasiform lesions can appear during effective treatment with dupilumab for atopic dermatitis, potentially reflecting a shift toward cutaneous IL-23/T 17 pathway activation with dupilumab-induced suppression of type 2 immunity.
Topics: Adult; Antibodies, Monoclonal, Humanized; Child; Dermatitis, Atopic; Eczema; Humans; Retrospective Studies
PubMed: 34647354
DOI: 10.1111/pde.14820 -
Biologics-Induced Immunophenotypic Cross-Switching in Patients with Psoriasis and Atopic Dermatitis.Indian Journal of Dermatology 2023Antibody-based therapies that inhibit pro-inflammatory cytokine signalling are commonly used in dermatology. Paradoxically, these biological agents may induce or... (Review)
Review
Antibody-based therapies that inhibit pro-inflammatory cytokine signalling are commonly used in dermatology. Paradoxically, these biological agents may induce or exacerbate paradoxical reactions. Recently, it has been reported that the treatment of eczema with dupilumab can lead to the development of psoriasiform eruptions, which we called psoriasiform paradoxical reactions (P-PRs). Conversely, cases of eczematous paradoxical reactions (E-PRs) have also been described in patients with psoriasis treated with biologics. To summarise the case characteristics and disease features of phenotypic transition between psoriasis and eczematoid dermatitis, and to explore the mechanism or connection related to biological agents or patients' genetic characteristics, a systematic review was conducted for P-PRs in atopic dermatitis and E-PRs in patients with psoriasis treated with corresponding biological agents, respectively. We identified a series of P-PRs in 42 atopic dermatitis cases treated with dupilumab. The time to onset of P-PRs typically ranged from weeks to months, with a mean latency period of 22.65 weeks. Almost all patients presented with new-onset P-PRs. Simultaneously, we reviewed 22 articles reporting 51 patients with psoriasis with biological agent-induced E-PRs, which occurred on average at 24.47 weeks, 72.55% of them induced by IL-17A inhibitors. 48.98% (24/49) of cases reported a positive personal history of atopy, which may suggest an increased risk of biological agent-induced paradoxical eruptions. Overall, the improvement or resolution upon discontinuation of the inciting biologics was relatively common, and further studies are needed to estimate the real prevalence and unveil the pathophysiological mechanisms of these paradoxical events.
PubMed: 37275804
DOI: 10.4103/ijd.ijd_871_22 -
Journal of the American Academy of... Nov 2020Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related... (Review)
Review
Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.
Topics: Drug Eruptions; Humans; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 32454097
DOI: 10.1016/j.jaad.2020.03.132