Dupilumab for pediatric prurigo nodularis: A case report Fachler, Tahel; Maria Faitataziadou, Sofia; Molho‐Pessach, Vered
Pediatric dermatology,
January/February 2021, 2021-Jan, 2021-01-00, 20210101, Letnik:
38, Številka:
1
Journal Article
Recenzirano
Herein we report on a 9‐year‐old girl with recalcitrant prurigo nodularis unresponsive to multiple standard treatments. She was started on dupilumab therapy with rapid improvement in pruritus within ...2 weeks and near complete regression of lesions at 3 months. Dupilumab should be considered as an off‐label treatment for refractory prurigo nodularis in children.
Tumor necrosis factor‐α inhibitor‐associated adverse cutaneous reactions are common in patients with inflammatory bowel disease. Infection‐related dermatoses and psoriasiform eruptions are seen most ...frequently. We describe a follicular psoriasiform eruption that appeared during treatment with infliximab in two adolescents with Crohn's disease.
Heterozygous STAT1 gain‐of‐function (GOF) mutations result in a combined form of immunodeficiency which is the most common genetic cause of chronic mucocutaneous candidiasis (CMC). We present a ...pedigree with a GOF mutation in STAT1, manifesting with chronic demodicosis in the form of a facial papulopustular eruption, blepharitis, and chalazion. So far, demodicosis has been described in only one family with STAT1‐GOF mutation. We suggest that chronic demodicosis is an under‐recognized feature of the immune dysregulation disorder caused by STAT1 gain‐of‐function mutations.
Acral peeling skin syndrome is a rare genodermatosis characterized by asymptomatic peeling of the acral skin. It is usually caused by biallelic mutations in the gene TGM5. However, biallelic ...mutations in the CSTA gene have also been described to cause APSS with exfoliative ichthyosis, so far in only five pedigrees. Here, we report two new pedigrees, each with one patient having APSS, due to a novel CSTA mutation.
Signal transducer and activator of transcription (STAT)1 heterozygous gain‐of‐function (GOF) mutations are known to induce immune dysregulation and chronic mucocutaneous candidiasis (CMCC). Previous ...reports suggest an association between demodicosis and STAT1 GOF. However, immune characterization of these patients is lacking. Here, we present a retrospective analysis of patients with immune dysregulation and STAT1 GOF who presented with facial and ocular demodicosis. In‐depth immune phenotyping and functional studies were used to characterize the patients. We identified five patients (three males) from two non‐consanguineous Jewish families. The mean age at presentation was 11.11 (range = 0.58–24) years. Clinical presentation included CMCC, chronic demodicosis and immune dysregulation in all patients. Whole‐exome and Sanger sequencing revealed a novel heterozygous c.1386C>A; p.S462R STAT1 GOF mutation in four of the five patients. Immunophenotyping demonstrated increased phosphorylated signal transducer and activator of transcription in response to interferon‐α stimuli in all patients. The patients also exhibited decreased T cell proliferation capacity and low counts of interleukin‐17‐producing T cells, as well as low forkhead box protein 3+ regulatory T cells. Specific antibody deficiency was noted in one patient. Treatment for demodicosis included topical ivermectin and metronidazole. Demodicosis may indicate an underlying primary immune deficiency and can be found in patients with STAT1 GOF. Thus, the management of patients with chronic demodicosis should include an immunogenetic evaluation.
Signal transducer and activator of transcription (STAT)1 gain‐of‐function (GOF) mutations are known to induce immune dysregulation. Immune phenotyping of these patients presenting with Demodex infection is lacking. Here, we summarize an in‐depth immune analysis of 5 patients with STAT1 GOF from 2 non‐consanguineous families presenting with chronic demodicosis. Thus, management of chronic demodicosis should include the evaluation of an underlying primary immune deficiency disorder.
H syndrome: The first 79 patients Molho-Pessach, Vered, MD; Ramot, Yuval, MD, MSc; Camille, Frances, MD ...
Journal of the American Academy of Dermatology,
01/2014, Letnik:
70, Številka:
1
Journal Article
Recenzirano
Background H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. Objective We sought to investigate the clinical and molecular findings in ...79 patients with this disorder. Methods A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. Results The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3 , with no genotype-phenotype correlation. Limitations In the 31 patients described by others, data were collected from the medical literature. Conclusions H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3 -related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients.
Autosomal dominant hyper-IgE syndrome (AD-HIES) caused by dominant negative (DN) variants in the signal transducer and activator of transcription 3 gene (
) is characterized by recurrent ...Staphylococcal abscesses, severe eczema, chronic mucocutaneous candidiasis (CMC), and non-immunological facial and skeletal features.
To describe our experience with the diagnosis and treatment of adult patients with AD-HIES induced by DN-
variants.
The medical records of adult patients (>18 years) treated at the Allergy and Clinical Immunology Clinic of Hadassah Medical Center, Jerusalem, Israel, were retrospectively analyzed. Immune and genetic workups were used to confirm diagnosis.
Three adult patients (2 males; age 29-41 years) were diagnosed with DN-
variants. All patients had non-immunological features, including coarse faces and osteopenia. Serious bacterial infections were noted in all patients, including recurrent abscesses, recurrent pneumonia, and bronchiectasis. CMC and diffuse dermatophytosis were noted in two patients. Two patients had severe atopic dermatitis refractory to topical steroids and phototherapy. Immune workup revealed elevated IgE in three patients and eosinophilia in two patients. Whole exome sequencing revealed DN-
variants (c.1166C>T; p.Thr389Ile in two patients and c.1268G>A; p. Arg423Gln in one patient). Variants were located in DNA-binding domain (DBD) and did not hamper STAT3 phosphorylation Treatment included antimicrobial prophylaxis with trimethoprim/sulfamethoxazole (n=2) and amoxycillin-clavulanic acid (n=1), and anti-fungal treatment with fluconazole (n=2) and voriconazole (n=1). Two patients who had severe atopic dermatitis, were treated with dupilumab with complete resolution of their rash. No adverse responses were noted in the dupilumab-treated patients.
Dupilumab can be used safely as a biotherapy for atopic dermatitis in these patients as it can effectively alleviate eczema-related symptoms. Immunologists and dermatologists treating AD-HIES adult patients should be aware of demodicosis as a possible manifestation. DN-
variants in DBD do not hamper STAT3 phosphorylation.
Background
Molluscum contagiosum (MC) is a common skin infection in the pediatric age group. The infection is self‐limited and manifests as discrete, umbilicated skin‐colored papules on any skin ...surface of the body. At times, complications such as local dermatitis and swelling, erythema, and pus formation may appear. These signs of inflammation are commonly presumed to represent bacterial infection.
Methods
This multicenter study was a retrospective analysis of data collected on all patients diagnosed with inflamed lesions secondary to MC and treated at the Hadassah Medical Centers and Shaare Zedek Medical Center in Jerusalem, Israel, from 1/1/2008 to 1/07/2018. Characteristics of children with positive cultures were compared to those with negative cultures and those with contaminants.
Results
A total of 56 cases were reviewed; the mean age at presentation was 4.6 years. Fever was reported in 12.5%, and 62.5% received systemic antibiotics because of their inflamed MC prior to admission. Fifty‐five percent had sterile cultures or cultures growing only contaminants. Only seven had positive cultures with the common cutaneous pathogens. No statistical difference was observed between the patients with pathogenic isolates and patients with sterile or non‐pathogenic cultures in terms of demographics, lesion characteristics, inflammatory markers, or length of hospitalization.
Conclusion
The findings suggest that most cases of suspected MC‐related secondary infection can be attributed to inflammation rather than to bacterial infection. However, in some cases, true bacterial infection should be suspected and treated accordingly.
TBC regimens are considered as “reduced toxicity” and are increasingly employed in pediatric HSCT. In our center, we commonly use the combination of treosulfan‐thiotepa‐fludarabine and ATG for ...pediatric non‐malignant diseases. As we often observe acute skin toxicities following this conditioning regimen, we conducted a prospective observational study to describe and characterize these toxicities. Fifteen pediatric patients undergoing HSCT for non‐malignant diseases who were treated at Hadassah‐Hebrew University Medical Center during 2015 were enrolled. A thorough dermatological assessment was done on days 0, 1, 7, and 14 from treatment initiation and included description of cutaneous reactions, measurement of BSA of affected skin, and response to local treatment. All the fifteen enrolled patients developed some degree of acute skin reaction. Cutaneous manifestations were variable and included erythematous patches in inguinal area and genitalia (80%), in neck and axillae (40%), diffuse hyperpigmentation (73%), erosions in inguinal area and buttock (47%), and xerosis and desquamation (40%). Average affected BSA reached 71.8%. Erosions were more prevalent in children younger than 2 years of age. The eruptions resolved without sequela in all patients and did not necessitate treatment other than topical agents. Observed extracutaneous toxicities included oral mucositis (40%), diarrhea (47%), and elevated liver enzymes (47%). TBC combined with thiotepa is highly toxic to the skin with various cutaneous manifestations. The toxicity resolves with no long‐term sequela.
