INDIVIDUAL ARTICLE: NECOM 3: A Practical Algorithm for the Management of Radiation Therapy-Related Acute Radiation Dermatitis.

BACKGROUND: In the Nordic European countries in 2020, cancer diagnoses accounted for 175,925 patients. About 50% of cancer patients receive radiation therapy (RT), which may lead to radiation dermatitis (RD). Notably, patients with breast, head, neck, and anal cancers may be prone to developing RD. However, few algorithms exist for the prevention and treatment of RD. METHODS: The Nordic European Cutaneous Oncodermatology Management (NECOM) project aims to improve cancer patient outcomes by offering tools to prevent and treat cancer therapy-related cutaneous adverse events (cAEs). The first 2 NECOM papers presented various cAEs and skincare regimens involving hygiene, moisturization, sun protection, and camouflage products for preventing and managing cAEs. The NECOM 3 practical algorithm for preventing and managing acute RD (ARD) is intended to promote healthy skin and reduce RT-related ARD, improving cancer patient outcomes.  Results: The NECOM advisors discussed the results of a systematic literature review and obtained consensus on the evidence and opinion-based practical algorithm for ARD to support all stakeholders in the Nordic European healthcare setting. The algorithm starts with skin-preserving therapy, followed by skin condition assessment and patient-specific interventions based on the grade of RD present.  Conclusion: ARD may lead to symptoms of pruritus and pain, decreased QoL and morbidity, and treatment interruptions. Patient education on the prevention of RD and treatment recommendations given in the NECOM 3 algorithm may help prevent and manage RD and improve the overall care of patients receiving RT. J Drugs Dermatol. 2023;22:11(Suppl 2):s3-s10.

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT).

BACKGROUND: Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb). METHODS: We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal-Wallis test. MFI 500 was used as threshold to define autoAb reactivity. RESULTS: A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009). CONCLUSIONS: Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).

Detection of novel therapies using a multi-national, multi-institutional registry of cutaneous immune-related adverse events and management.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias. METHODS: Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv. RESULTS: Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated. CONCLUSION: This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made.

US Cutaneous Oncodermatology Management (USCOM): A Practical Algorithm.

BACKGROUND: An increasing number of patients survive or are living with cancer. Anticancer treatments frequently have cutaneous adverse events (cAEs) that may severely impact patients' quality of life and interrupt anticancer treatment. The US Cutaneous Oncodermatology Management (USCOM) project aims to improve cancer patients' and survivors' quality of life by offering tools for preventing and managing cAEs. METHODS: An algorithm was designed to reduce the incidence of cAEs, treat cAEs, and maintain healthy skin using general measures and over-the-counter agents to support all healthcare providers treating oncology patients, including physicians, nurses, pharmacists, and advanced providers. The panel used a modified Delphi approach, developed, discussed, and reached a consensus on statements and an evidence-based algorithm. RESULTS: The USCOM algorithm includes education on cAEs for patients and clinicians supporting prevention, treatment, and maintenance using skincare measures before, during, and after cancer treatment. A skincare regimen including hygiene, moisturization, and sun protection products should be safe and effective in helping to minimize cAEs and improving skin conditions such as erythema, xerosis, pruritus, and photosensitivity. The number and quality of studies evaluating skincare formulations and regimens for cAEs are increasing, but the evidence on the benefits of specific formulations is still scarce. CONCLUSIONS: The algorithm focuses on general measures and skincare to prevent or reduce the severity of cAEs. Increased awareness of cAEs by the multidisciplinary team treating and guiding the cancer patient throughout their care may improve patient outcomes. J Drugs Dermatol. 2021;20:9(Suppl):s3-19.

Skin Surface pH

The role of skin surface pH, also referred to as "acid mantle," was described more than 90 years ago and due to developing insights has now returned into focus.1

Clinical Insights About the Role of pH in Acne

Acne vulgaris is the most common dermatological disorder globally.1,2 Psychological and emotional distress due to acne, including poor self-esteem, social anxiety, depression, and suicidal ideation have been reported in various studies.3,4, Acne is a complex multifactorial disease with its pathophysiology incompletely elucidated.

Derivation, Evaluation, and Validation of Illustrations of Key Counselling Points for a Pediatric Eczema Action Plan.

BACKGROUND: Current eczema action plans (EAP) are based on written instructions without illustrations. Incorporating validated illustrations into EAPs can significantly improve comprehension and usability. OBJECTIVE: To produce and validate a set of illustrations for key counselling points of a pediatric EAP. METHODS: Illustrations were developed using key graphic elements and refined by subject experts. Illustrations were evaluated during one-on-one structured interviews with parents/caregivers of children ages 9 and younger, as well as with children ages 10 to 17 years between September 2015 and June 2016. The concepts of transparency, translucency, and short-term recall were assessed for validation. RESULTS: Of 245 participants, 81.3% were parents and/or caregivers of children 0 to 9 years old, and 18.7% were children between 10 and 17 years old. A total of 15 illustrations and 2 storyboards were evaluated; 9 illustrations and 2 storyboards were redesigned to reach the preset validation targets. Overall, 13 illustrations and 2 storyboards were validated. CONCLUSION: A set of illustrations for use in an EAP was prospectively designed and validated, achieving acceptable transparency, translucency, and recall, with input from patients and a multidisciplinary medical team. The incorporation of validated illustrations into eczema action plans benefits patients with limited health literacy. Future studies should evaluate if illustrations improve understanding of eczema management and translate into improved clinical outcomes.

CD30+ Lymphoproliferative Disorders of the Skin.

Primary cutaneous CD30+ lymphoproliferative disorders encompass lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL), and indeterminate cases. LyP is a benign disorder characterized by recurrent crops of red or violaceous papulonodules. Patients with LyP are at an increased risk of a secondary malignancy. pcALCL is characterized by a solitary red to violaceous nodule or tumor larger than 20 mm. LyP is benign, is limited to the skin, and self-resolves, with a 5-year survival rate of 100%; pcALCL is limited to the skin and responsive to directed therapies, with a 5-year survival rate of over 95%. Aggressive chemotherapeutic regimens should be avoided.

The Effectiveness of Written Action Plans in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic dermatosis requiring a stepwise and dynamic approach to management. The use of written action plans has been shown to improve outcomes in other chronic diseases that require a similar incremental approach. A systematic review was performed to evaluate the effect of a written eczema action plan (EAP) in AD management and to identify characteristics of effective action plans in children with eczema. Only two trials were identified as eligible, which highlights the need for more research on EAPs.

Acrylate Systemic Contact Dermatitis.

Acrylates, the 2012 American Contact Dermatitis Society allergen of the year, are found in a range of products including the absorbent materials within feminine hygiene pads. When fully polymerized, acrylates are nonimmunogenic; however, if not completely cured, the monomers can be potent allergens.A 28-year-old woman is presented, who had her teeth varnished with Isodan (Septodont, Saint-Maur-des-Fossés, France) containing HEMA (2-hydroxyethyl methacrylate) with no initial reaction. Approximately 1 month later, the patient developed a genital dermatitis secondary to her feminine hygiene pads. The initial reaction resolved, but 5 months later, the patient developed a systemic contact dermatitis after receiving a second varnishing.The patient was dramatically patch test positive to many acrylates. This case demonstrates a reaction to likely unpolymerized acrylates within a feminine hygiene pad, as well as broad cross-reactivity or cosensitivity to acrylates, and possibly a systemic contact dermatitis with systemic re-exposure to unpolymerized acrylates.

Acitretin-induced hepatitis: when to monitor cholestatic enzymes.

IMPORTANCE: Acitretin is a systemic retinoid that is used in dermatology for a variety of conditions. A well-recognized potential adverse event from acitretin is elevated transaminases, indicating acute hepatocyte damage. Less well known is the possible cholestatic injury that can occur, signaled by elevated γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP). OBSERVATIONS: Our patient presented with an acute acitretin-induced hepatitis with a mixed pattern of elevated transaminases as well as GGT and ALP. A literature review demonstrated that most cases of acitretin-induced hepatitis, outside clinical trials, describe patients with a similar mixed hepatitis pattern. CONCLUSIONS: This is the first literature review on acitretin-induced hepatitis. Although acitretin-induced hepatoxicity is rare, the seemingly unusual presentation of a mixed pattern of hepatocyte injury and cholestasis may be more common than previously thought. The findings should encourage clinicians not only to monitor transaminases but also to consider measuring cholestatic enzymes (ALP/GGT) in patients with transaminase abnormalities.

Extragenital bullous lichen sclerosus.

Lichen sclerosus is an inflammatory skin condition characterized by inflammation of the papillary dermis that leads to white scarlike plaques. It occurs classically in the genitals but also has extragenital manifestations with a variety of clinical presentations including a bullous variant. The purpose of this review is to characterize extragenital bullous lichen sclerosus, suggest that it may be more common than dermatologists realize, and discuss treatment of both routine and recalcitrant cases.

Novel use of polymethyl methacrylate (PMMA) microspheres in the treatment of infraorbital rhytids.

AIM: To demonstrate safely with the use of polymethyl methacrylate (PMMA) microspheres in the infraorbital eyelid area using a deliberate conservative injection in the treatment of rhytids. METHODS: A retrospective case series of 289 patients in an outpatient cosmetic dermatology clinic evaluated and treated by one senior provider (NM) of infraorbital rhytids with PMMA from December 2010 to March 2011. Statistical analysis was performed for race, skin type, history of hypertrophic scar, autoimmunity, history of "sensitive skin" and history of prior procedures such as prior facelift, rhinoplasty, and blepharoplasty. RESULTS: Two hundred ninety-one patients underwent at least 1-6 injections of PMMA microspheres into bilateral under eye area. Early complications were edema and ecchymosis. Late complications were identified in 4 of 289 patients who developed small granulomas. All patients who developed granulomas had had a previous lower blepharoplasty (P = 0.00). A history of "sensitive skin" was approaching statistical significance (P = 0.15). CONCLUSION: This study has shown that PMMA microsphere injection is a safe subdermal technique in the correction of infraorbital rhytids. Safety was demonstrated in 289 patients with only 4 minor complications of small lateral granuloma which all resolved within 4 weeks after intralesion triamcinolone injection. However, this is an off-label use of a permanent filler not approved for use in the infraorbits and significant caution must be taken with full disclosure to the patient leading to informed consent. Caution in PMMA microsphere injection should be given in the patient with prior blepharoplasty. The advantage of PMMA microsphere is that the result seems to be predictable and natural.

Palmoplantar subcorneal pustular dermatosis following adalimumab therapy for rheumatoid arthritis.

BACKGROUND: Tumour necrosis factor (TNF)-α inhibitors represent potent new therapies for severe forms of psoriasis, psoriatic arthritis, and several other immune-mediated disorders. Paradoxical worsening or de novo development of psoriasis has been documented with their use. Palmoplantar pustulosis has been one of the commoner presentations of this unusual side effect. Subcorneal pustular dermatosis (SPD) has some similarity to pustular psoriasis, particularly the acral form of SPD. Thus far there have been no biopsy-proven cases of SPD associated with TNF-α inhibitor use. METHODS: We describe clinical and histopathological features of a pustular skin condition which occurred in a 48-year-old woman with rheumatoid arthritis who had started adalimumab four months prior. The adalimumab had been added to her usual treatment with methotrexate because of incomplete symptom control. RESULTS: Painful and pruritic skin lesions were noted on her palms and soles primarily, with some extension to the limbs and abdomen. Examination revealed relatively non-inflamed pustules with fluid levels, together with sparse crusted papules. Histopathology showed subcorneal pustules more suggestive of SPD than pustular psoriasis. The eruption resolved completely when adalimumab was withdrawn; methotrexate was continued. CONCLUSION: Subcorneal pustular dermatosis, in addition to psoriasis vulgaris and pustular psoriasis, may occur in patients treated with TNF-α inhibitors like adalimumab.

Basal Cell Carcinoma in Type 2 Segmental Darier's Disease.

Background. Darier's disease (DD), also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002). Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC) arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.