Immune profiling of lupus miliaris disseminatus faciei and successful management with anti-tumour necrosis factor therapy.

Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiology, most often seen in young adults. Although many treatments for LMDF exist, treatment guidelines have not been developed, and response to therapy is generally unpredictable. We present the results of transcriptomic analysis of LMDF lesional skin, which revealed a variety of differentially expressed genes linking LMDF to alterations in innate and adaptive T helper 1 immunity. Immunohistochemical analysis was also performed, identifying similar changes in T-cell immune responses. Given evidence for increased tumour necrosis factor (TNF) pathway activity, our patient, who had previously been refractory to multiple treatments, was initiated on TNF inhibitor therapy with excellent response. This characterization of the LMDF immune response may lead to improved treatment of this condition.

Histopathological and immunohistochemical features of facial papules in frontal fibrosing alopecia.

BACKGROUND: Facial papules (FPs) are considered to be created by the inflammatory process, which involves facial vellus hairs, in frontal fibrosing alopecia. AIM: To demonstrate the histopathological features of FPs and the composition of the inflammatory infiltrate. METHODS: In total, 18 patients with FPs were enrolled in the study after histopathological confirmation of lichen planopilaris. Histopathological evaluation of the specimens was performed by two dermatopathologists. The samples were immunostained with CD4, CD8 and CD123 monoclonal antibodies, and the percentage and proportion of cells stained with these markers were investigated. RESULTS: A follicular lichenoid reaction and perifollicular fibrosis were present in all cases. Vellus hairs were detected in 83.3% of biopsy specimens (15 cases), all of which were involved by the inflammation. The majority of the follicles (72%) revealed follicular plugs. Reduction and destruction of elastic fibres were visible in the perifollicular (adventitial) and the papillary dermis (100% and 78% of specimens, respectively). Prominent sebaceous glands and dilated ducts were detected in 78% and 72% of samples, respectively. CD4-positive T cells formed 67.72% and CD8-positive T cells 32.28% of the infiltrate, and the mean CD4/CD8 ratio was 2.48. In 13 (72.2%) biopsy specimens < 10% of the infiltrate was positive for CD123 marker. CONCLUSIONS: Perifollicular inflammation, fibrosis and elastic-fibre destruction were constant histopathological features of FPs; furthermore, prominent sebaceous glands were present in the majority of samples. We also observed a CD4-positive predominance in the infiltrate.

Rosacea: New Concepts in Classification and Treatment.

Rosacea is a chronic inflammatory dermatosis mainly affecting the cheeks, nose, chin, and forehead. Rosacea is characterized by recurrent episodes of flushing or transient erythema, persistent erythema, phymatous changes, papules, pustules, and telangiectasia. The eyes may also be involved. Due to rosacea affecting the face, it has a profound negative impact on quality of life, self-esteem, and well-being. In addition to general skin care, there are several approved treatment options available for addressing these features, both topical and systemic. For some features, intense pulse light, laser, and surgery are of value. Recent advances in fundamental scientific research have underscored the roles of the innate and adaptive immune systems as well as neurovascular dysregulation underlying the spectrum of clinical features of rosacea. Endogenous and exogenous stimuli may initiate and aggravate several pathways in patients with rosacea. This review covers the new phenotype-based diagnosis and classification system reflecting pathophysiology, and new and emerging treatment options and approaches. We address new topical and systemic formulations, as well as recent evidence on treatment combinations. In addition, ongoing studies investigating novel therapeutic interventions will be summarized.

Facial and neck erythema associated with dupilumab treatment: A systematic review.

BACKGROUND: Neither dupilumab-associated facial erythema nor neck erythema was reported in phase 3 clinical trials for the treatment of atopic dermatitis, but there have been a number of reports of patients developing this adverse event in clinical practice. OBJECTIVE: To outline all cases of reported dupilumab-associated facial or neck erythema to better characterize this adverse event, and identify potential etiologies and management strategies. METHODS: A search was conducted on EMBASE and PubMed databases. Two independent reviewers identified relevant studies for inclusion and performed data extraction. RESULTS: A total of 101 patients from 16 studies were reported to have dupilumab-associated facial or neck erythema. A total of 52 of 101 patients (52%) had baseline atopic dermatitis facial or neck involvement and 45 of 101 (45%) reported different cutaneous symptoms from preexisting atopic dermatitis, possibly suggesting a different etiology. Suggested etiologies included rosacea, allergic contact dermatitis, and head and neck dermatitis. Most commonly used treatments included topical corticosteroids, topical calcineurin inhibitors, and antifungal agents. In the 57 patients with data on the course of the adverse events, improvement was observed in 29, clearance in 4, no response in 16, and worsening in 8. A total of 11 of 101 patients (11%) discontinued dupilumab owing to this adverse event. LIMITATIONS: Limited diagnostic testing, nonstandardized data collection and reporting across studies, and reliance on retrospective case reports and case series. CONCLUSION: Some patients receiving dupilumab develop facial or neck erythema that differs from their usual atopic dermatitis symptoms. Prompt identification and empiric treatment may minimize distress and potential discontinuation of dupilumab owing to this adverse event.

Single nucleotide variations in genes associated with innate immunity are enriched in Japanese adult cases of face and neck type atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood. OBJECTIVE: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features. METHODS: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients. RESULTS: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD. CONCLUSION: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.

Facial Dermatitis in Male Patients Referred for Patch Testing: Retrospective Analysis of North American Contact Dermatitis Group Data, 1994 to 2016.

Importance: Facial dermatitis in women is well characterized. However, recent shifts in the men's grooming industry may have important implications for male facial dermatitis. Objective: To characterize male patients with facial dermatitis. Design, Setting, and Participants: A 22-year retrospective cross-sectional analysis (1994-2016) of North American Contact Dermatitis Group (NACDG) data, including 50 507 patients who underwent patch testing by a group of dermatology board-certified patch test experts at multiple centers was carried out. Facial dermatitis was defined as involvement of the eyes, eyelids, lips, nose, or face (not otherwise specified). Main Outcomes and Measures: The main outcome was to compare characteristics (including demographics and allergens) between male patients with facial dermatitis (MFD) and those without facial dermatitis (MNoFD) using statistical analysis (relative risk, CIs). Secondary outcomes included sources of allergic and irritant contact dermatitis and, for occupationally related cases, specific occupations and industries in MFD. Results: Overall, 1332 male patients (8.0%) were included in the MFD group and 13 732 male patients (82.0%) were included in MNoFD. The mean (SD) age of participants was 47 (17.2) years in the MFD group and 50 (17.6) years in the MNoFD group. The most common facial sites were face (not otherwise specified, 817 [48.9%]), eyelids (392 [23.5%]), and lips (210 [12.6%]). Participants in the MFD group were significantly younger than MNoFD (mean age, 47 vs 50 years; P < .001). Those in the MFD group were less likely to be white (relative risk [RR], 0.92; 95% CI, -0.90 to 0.95) or have occupationally related skin disease (RR, 0.49; 95% CI, -0.42 to 0.58; P < .001) than MNoFD. The most common allergens that were associated with clinically relevant reactions among MFD included methylisothiazolinone (n = 113; 9.9%), fragrance mix I (n = 27; 8.5%), and balsam of Peru (n = 90; 6.8%). Compared with MNoFD, MFD were more likely to react to use of dimethylaminopropylamine (RR, 2.49; 95% CI, -1.42 to 4.37]) and paraphenylenediamine (RR, 1.43; 95% CI, -1.00 to 2.04; P < .001). Overall, 60.5% of NACDG allergen sources were personal care products. Conclusions and Relevance: Although many allergens were similar in both groups, MFD were more likely to react to use of dimethylaminopropylamine and paraphenylenediamine, presumably owing to their higher prevalence in hair products. Most sources of allergic and irritant contact dermatitis in MFD were personal care products. This study provides insight into the risks and exposures of the increasing number of grooming products used by male dermatology patients. This will enable clinicians to better identify male patients who would benefit from patch testing and treat those with facial dermatitis.

Delayed-Onset Nodules to Differentially Crosslinked Hyaluronic Acids: Comparative Incidence and Risk Assessment.

BACKGROUND: Robust and long-term data on true incidence of delayed-onset nodules and immune tolerance of hyaluronic acid (HA) fillers are lacking. OBJECTIVE: To characterize the incidence of delayed nodules in Vycross (VYC) HA fillers compared with previously reported FDA and non-FDA data of all HA fillers. METHODS AND MATERIALS: The incidence of delayed nodules in all patients who had received VYC fillers in a 12-month period was assessed through a retrospective chart review. Nodule incidence for currently approved nonanimal-stabilized hyaluronic acid (NASHA) fillers was assessed using the FDA Summary of Safety and Effectiveness Data. RESULTS: Overall, 1,029 patients received 1,250 VYC filler treatments. Five patients developed delayed nodules to VOB, with an incidence of 1.0% per patient and 0.8% per syringe. No nodules were observed in patients who received VLR or VOL. All nodules were treated successfully using a combination of intralesional triamcinolone and hyaluronidase. Compared with other currently approved NASHA fillers, VOB is associated with a higher incidence of nodule formation. CONCLUSION: The introduction of VYC HAs has introduced a new variable that may be changing the immune tolerance of these substances, resulting in a higher incidence of delayed nodules than previously expected.

Erythematotelangiectatic rosacea may be associated with a subclinical stage of demodicosis: a case-control study.

BACKGROUND: Facial densities of Demodex mites have been observed to be greater in patients with demodicosis and papulopustular rosacea than in healthy control patients. In patients with erythematotelangiectatic rosacea (ETR), this density has been observed to be similar to or greater than that of healthy controls. Erythema and telangiectasia, characteristics of ETR, are often observed among patients with pityriasis folliculorum, a discreet demodicosis, suggesting a possible link between these conditions. OBJECTIVES: To compare the facial Demodex densities of patients with clinical ETR and patients with healthy skin, demodicosis, rosacea with papulopustules, and other facial dermatoses. METHODS: In this retrospective study, we recorded Demodex densities measured using two consecutive standardized skin surface biopsies (SSSB1 and SSSB2) in 23 patients with ETR, 20 healthy control patients, 590 patients with demodicosis, 254 with rosacea with papulopustules and 180 with other facial dermatoses. RESULTS: Patients with ETR had higher Demodex densities (D cm-2 ) than did the healthy controls (mean ± SEM; SSSB1: 15·7 ± 6·3 vs. 1·8 ± 1·1 D cm-2 , P = 0·042; SSSB2: 38·0 ± 13·7 vs. 5·1 ± 2·1 D cm-2 , P = 0·026) and patients with other dermatoses (SSSB1: 0·4 ± 0·1 D cm-2 , P = 0·004; SSSB2: 1·3 ± 0·3 D cm-2 , P = 0·004), but lower densities than patients with demodicosis (SSSB1: 82·7 ± 4·2 D cm-2 , P = 0·008; SSSB2: 172·2 ± 7·7 D cm-2 , P = 0·001) or rosacea with papulopustules (SSSB1: 86·6 ± 7·3 D cm-2 , P = 0·027; SSSB2: 197·0 ± 12·1 D cm-2 , P = 0·002). CONCLUSIONS: ETR may be associated with nonvisible Demodex proliferation, possibly corresponding to a subclinical stage of demodicosis. Dermatologists should be aware of this potential association and look for subclinical demodicosis in patients with ETR, so that topical acaricidal treatment can be offered if Demodex density is high.

Comparative Study of the Clinical Pathology, Immunophenotype, Epstein-Barr Virus Infection Status, and Gene Rearrangements in Adult and Child Patients With Hydroa Vacciniforme-Like Lymphoproliferative Disorder.

BACKGROUND: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein-Barr virus (EBV)-associated lymphoma that mainly affects children. OBJECTIVES: To examine the similarities and differences in the clinical pathological features, EBV infection status, and gene rearrangements in adults and children patients with HVLPD. METHODS: We compared the clinical manifestations, histopathology, immunophenotypical features, EBV infection status, and T-cell receptor gene rearrangements in the adult and children HVLPD groups. RESULTS: Clinical manifestations differed between children and adults groups. The children were characterized by blisters and severe facial swelling, whereas the adults were characterized by mild facial swelling and papules. Mosquito bite was significantly related to morbidity in the children group. Histologically, the number of mast cells in the adult group was greater than in the children group (P < 0.05). There were no significant differences in EBV infection status or TCR-γ gene rearrangements between 2 groups. CONCLUSIONS: There were differences in clinical pathology and prognosis between the 2 groups. A higher mast cell count and T-cell phenotype might be associated with a poor prognosis.

Rosacea and Demodicosis: Little-known Diagnostic Signs and Symptoms.

Papulopustular rosacea and demodicosis are characterized by non-specific symptoms, which can make clinical diagnosis difficult. This retrospective study of 844 patients assessed the diagnostic importance of clinical signs and symptoms that are poorly recognized as being associated with these conditions. In addition to well-known signs (vascular signs (present in 80% of patients), papules (39%), pustules (22%) and ocular involvement (21%)), other signs and symptoms (discreet follicular scales (93%), scalp symptoms (pruritus, dandruff or folliculitis; 38%) and pruritus (15%)) may also suggest a diagnosis not only of demodicosis, but also of papulopustular rosacea. Facial Demodex densities (measured by 2 consecutive standardized skin biopsies) were higher when ocular or scalp involvement was present, suggesting more advanced disease, but further investigations are needed to confirm this hypothesis. Recognition of these clinical signs and symptoms should encourage dermatologists to perform a Demodex density test, thus enabling appropriate diagnosis to be made.