Dermatology

Review: Chronic Hand Eczema

29 Nov, 2024 | 12:28h | UTC

Introduction: Hand eczema is a highly prevalent inflammatory skin condition and one of the most common work-related disorders, with a lifetime prevalence of approximately 15%. In up to two-thirds of affected individuals, the disease becomes chronic—persisting for more than three months or recurring multiple times within a year—leading to substantial personal and occupational disability. This review by Weidinger and Novak synthesizes current knowledge on the epidemiology, risk factors, clinical features, diagnosis, mechanisms, and management of chronic hand eczema, highlighting the need for further research to enhance prevention and treatment strategies.

Key Recommendations:

Risk Factor Identification: Recognize major risk factors, including current or past atopic dermatitis, dry skin, and occupational exposure to irritants and allergens. Occupational history is crucial, as hand eczema is prevalent in high-risk professions such as health care, hairdressing, and cleaning.
Diagnosis and Assessment: Diagnose chronic hand eczema based on history and clinical features, considering differential diagnoses like psoriasis and tinea manus. Patch testing is recommended to identify contact allergens, especially in cases unresponsive to initial therapy.
Patient Education and Prevention: Implement structured education on skin care, avoidance of trigger factors, and use of protective measures. Emphasize primary to tertiary prevention strategies, including workplace interventions and rehabilitation programs.
Topical Therapies: Initiate treatment with topical glucocorticosteroids for anti-inflammatory effect. Use calcineurin inhibitors as second-line therapy, particularly for patients refractory to steroids or requiring long-term treatment. The topical pan-Janus kinase inhibitor delgocitinib is approved for moderate to severe chronic hand eczema unresponsive to corticosteroids.
Phototherapy: Consider short-term phototherapy (4–8 weeks) with options like PUVA or narrow-band UVB for patients inadequately controlled with topical treatments.
Systemic Therapies: For severe cases unresponsive to topical treatments, systemic retinoids such as alitretinoin are first-line therapy. Off-label use of immunosuppressants like ciclosporine, methotrexate, and azathioprine may be considered. Systemic immunomodulatory therapies approved for atopic dermatitis, including dupilumab and Janus kinase inhibitors, show promise, especially in atopic hand eczema.
Adjunctive Measures: Encourage the use of emollients for skin barrier repair and recommend avoidance of harmful exposures. Patient self-management is crucial, including appropriate hand hygiene and use of protective gloves.

Conclusion: By adopting these evidence-based management strategies, clinicians can improve patient care by reducing symptoms, preventing disease progression, and enhancing quality of life for individuals with chronic hand eczema. Early identification of risk factors, comprehensive patient education, and individualized treatment plans are essential to mitigate the substantial personal and socioeconomic burden of this condition.

Reference: Weidinger S, Novak N. Hand eczema. The Lancet. 2024. DOI: http://doi.org/10.1016/S0140-6736(24)01810-5

Consensus Guideline: Low-Dose Oral Minoxidil for Hair Loss Management

24 Nov, 2024 | 20:27h | UTC

Introduction: Hair loss significantly affects patients’ quality of life, encompassing conditions like androgenetic alopecia, alopecia areata, and telogen effluvium. While topical minoxidil is FDA-approved for certain hair loss types, limitations have led to increased off-label use of low-dose oral minoxidil (LDOM). Recognizing the need for standardized guidance, an international panel of 43 dermatologists from 12 countries developed a consensus statement using a modified Delphi process to inform best practices for prescribing LDOM until more robust evidence emerges.

Key Recommendations:

Patient Selection:
- Indications: LDOM may benefit adults and adolescents with androgenetic alopecia, age-related thinning, alopecia areata, telogen effluvium, traction alopecia, persistent chemotherapy-induced alopecia, and endocrine therapy–induced alopecia.
- Contraindications: LDOM is contraindicated in patients with hypersensitivity to minoxidil, significant drug interactions, history of pericardial effusion or tamponade, pericarditis, congestive heart failure, pulmonary hypertension with mitral stenosis, pheochromocytoma, and during pregnancy or breastfeeding.
- Precautions: Use cautiously in patients with tachycardia, arrhythmias, hypotension (blood pressure <90/60 mm Hg), impaired kidney function, or those undergoing dialysis.
Dosing Guidelines:
- Adults:
  - Females: Starting dose of 1.25 mg daily; dosing range 0.625 mg to 5 mg daily.
  - Males: Starting dose of 2.5 mg daily; dosing range 1.25 mg to 5 mg daily.
- Adolescents (12–17 years):
  - Females: Starting dose of 0.625 mg daily; dosing range 0.625 mg to 2.5 mg daily.
  - Males: Starting dose of 1.25 mg daily; dosing range 1.25 mg to 5 mg daily.
- Considerations: Dosing influenced by sex, age, risk of systemic adverse effects, and desire to minimize hypertrichosis.
Monitoring and Evaluation:
- Baseline Assessments: Routine labs and ECGs are not required unless precautions are present; consult specialists if needed.
- Adverse Effects Monitoring: Counsel patients on potential side effects like hypertrichosis, dizziness, tachycardia, and fluid retention; monitor for signs such as swelling or weight gain.
- Efficacy Expectations: Initial effects may be observed at three months; efficacy may take up to six months if transient shedding occurs.
Adjunctive Therapies:
- Spironolactone: May be co-administered in female patients with hirsutism, acne, or polycystic ovary syndrome to enhance treatment efficacy and manage fluid retention.
- Beta-Blockers: Consider in consultation with specialists, especially for managing tachycardia.
Preference Over Topical Minoxidil:
- LDOM may be preferred when topical minoxidil causes scalp irritation, is cosmetically unacceptable, ineffective, or when enhanced hypertrichosis is desired.

Conclusion: This consensus provides a structured approach for clinicians considering LDOM as an off-label treatment for hair loss. By outlining patient selection, dosing, monitoring, and when to seek specialist input, these recommendations aim to optimize patient outcomes and safety.

Reference: Akiska YM, et al. Low-Dose Oral Minoxidil Initiation for Patients With Hair Loss: An International Modified Delphi Consensus Statement. JAMA Dermatology. 2024. DOI: http://doi.org/10.1001/jamadermatol.2024.4593

RCT: Nivolumab Plus Ipilimumab Shows Sustained 10-Year Survival Benefit in Advanced Melanoma

18 Sep, 2024 | 15:06h | UTC

Background: Advanced melanoma historically had a poor prognosis, with median survival under 12 months before 2011. The advent of immune checkpoint inhibitors like nivolumab (anti–PD-1) and ipilimumab (anti–CTLA-4) has significantly improved outcomes. Previous results from the CheckMate 067 trial showed longer overall survival with nivolumab plus ipilimumab or nivolumab alone compared to ipilimumab alone. As patients now live beyond 7.5 years, longer-term data are needed to address new clinical questions about survival and disease progression.

Objective: To assess the final 10-year outcomes of overall survival, melanoma-specific survival, and response durability in patients with advanced melanoma treated with nivolumab plus ipilimumab, nivolumab monotherapy, or ipilimumab monotherapy.

Methods: In the phase 3 CheckMate 067 trial, 945 patients with untreated, unresectable stage III or IV melanoma were randomized 1:1:1 to receive:

Nivolumab plus ipilimumab: Nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for four doses, then nivolumab (3 mg/kg) every 2 weeks.
Nivolumab monotherapy: Nivolumab (3 mg/kg) every 2 weeks plus placebo.
Ipilimumab monotherapy: Ipilimumab (3 mg/kg) every 3 weeks for four doses plus placebo.

Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Randomization was stratified by BRAF mutation status, metastasis stage, and PD-L1 expression. Primary endpoints were overall survival and progression-free survival; secondary endpoints included objective response rates and subgroup analyses.

Results: After 10 years, median overall survival was:

71.9 months with nivolumab plus ipilimumab,
36.9 months with nivolumab,
19.9 months with ipilimumab.

Hazard ratios for death were 0.53 (95% CI, 0.44–0.65; P<0.001) for nivolumab plus ipilimumab vs. ipilimumab, and 0.63 (95% CI, 0.52–0.76; P<0.001) for nivolumab vs. ipilimumab. Ten-year overall survival rates were 43% with combination therapy, 37% with nivolumab, and 19% with ipilimumab. Median melanoma-specific survival was not reached (>120 months) with combination therapy (37% alive at study end), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with combination therapy, 97% with nivolumab, and 88% with ipilimumab. No new safety signals were observed over the extended follow-up.

Conclusions: Nivolumab plus ipilimumab demonstrated a sustained 10-year survival benefit over ipilimumab monotherapy in advanced melanoma. Nivolumab monotherapy also improved survival compared to ipilimumab, though the combination provided the greatest benefit.

Implications for Practice: These 10-year results support nivolumab plus ipilimumab as a preferred first-line treatment for advanced melanoma, offering potential for long-term survival and possible cure. Clinicians should balance improved efficacy against higher adverse event rates with combination therapy and monitor patients accordingly.

Study Strengths and Limitations: Strengths include the large, randomized, multicenter design and extended follow-up, providing robust survival data. Limitations include the trial not being powered for formal comparison between combination and monotherapy, and potential confounding from subsequent therapies on long-term outcomes.

Future Research: Further studies should aim to identify biomarkers predicting long-term response, optimize patient selection for combination therapy, and develop treatments for patients unresponsive to current immune checkpoint inhibitors.

Reference: Wolchok JD, et al. (2024). Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. New England Journal of Medicine. 2024. DOI: http://doi.org/10.1056/NEJMoa2407417

RCT: Zasocitinib Achieves Significant Psoriasis Improvement in Moderate to Severe Plaque Psoriasis

6 Sep, 2024 | 22:48h | UTC

Study Design and Population: This phase 2b, double-blind, placebo-controlled trial evaluated the efficacy, safety, and tolerability of zasocitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, in patients with moderate to severe plaque psoriasis. Conducted across 55 centers in the US and Canada, the study enrolled 287 patients aged 18 to 70 years with a Psoriasis Area and Severity Index (PASI) score ≥12, and ≥10% of body surface area affected. Patients were randomized to receive zasocitinib at doses of 2 mg, 5 mg, 15 mg, or 30 mg, or a placebo, over 12 weeks.

Main Findings: At week 12, significant improvements in PASI were observed across all doses of zasocitinib. The primary endpoint of PASI 75 was achieved in 18%, 44%, 68%, and 67% of patients in the 2 mg, 5 mg, 15 mg, and 30 mg zasocitinib groups, respectively, compared to 6% in the placebo group. Higher PASI 90 and PASI 100 responses were also observed, particularly in the 15 mg and 30 mg groups. Adverse events were mild to moderate and occurred in 53% to 62% of patients receiving zasocitinib, compared to 44% for placebo.

Implications for Practice: Zasocitinib shows promise as an effective and well-tolerated oral treatment for moderate to severe plaque psoriasis. Its efficacy in achieving skin clearance (PASI 75 and above) at higher doses suggests potential for broader clinical use, with phase 3 trials warranted for further validation.

Reference: Armstrong, A.W. et al. (2024). Tyrosine Kinase 2 Inhibition with Zasocitinib in Psoriasis: A Randomized Clinical Trial. JAMA Dermatology. http://doi.org/10.1001/jamadermatol.2024.2701

Network Meta-Analysis: Potent Corticosteroids, JAK Inhibitors, and Tacrolimus 0.1% Among the Most Effective Topical Treatments for Eczema – Cochrane Library

25 Aug, 2024 | 12:03h | UTC

Study Design and Population: This network meta-analysis included 291 randomized controlled trials involving 45,846 participants with varying eczema severity. The trials primarily focused on adults in high-income countries and assessed various topical anti-inflammatory treatments over a median duration of 21 to 28 days. The study aimed to compare the efficacy and safety of these treatments.

Main Findings: Potent topical corticosteroids (TCS), JAK inhibitors, and tacrolimus 0.1% were consistently ranked as the most effective treatments for reducing eczema symptoms and signs. In contrast, phosphodiesterase-4 (PDE-4) inhibitors like crisaborole 2% and mild TCS were among the least effective. Notably, tacrolimus, pimecrolimus, and crisaborole were more likely to cause local adverse effects such as burning and stinging, while short-term TCS use did not show an increased risk of skin thinning, although long-term use did.

Implications for Practice: The findings suggest that potent TCS, JAK inhibitors, and tacrolimus 0.1% are effective for short-term eczema control. However, given the risk of skin thinning with long-term TCS use and potential adverse effects with certain treatments, clinicians should consider patient preferences, treatment availability, and cost when selecting therapies.

Reference: Cochrane Skin Group, et al. (2024). Topical anti-inflammatory treatments for eczema: network meta-analysis. Cochrane Database of Systematic Reviews. http://doi.org/10.1002/14651858.CD015064.pub2

RCT: Nemolizumab Plus Topical Therapy Improves Skin Clearance, Itch, and Sleep in Moderate-to-Severe Atopic Dermatitis – The Lancet

11 Aug, 2024 | 12:58h | UTC

Study Design and Population: This study reports on two identical 48-week, double-blind, randomized, placebo-controlled phase 3 trials (ARCADIA 1 and ARCADIA 2) involving 1,728 adolescents and adults with moderate-to-severe atopic dermatitis and pruritus unresponsive to topical corticosteroids. Participants were randomized 2:1 to receive nemolizumab (an IL-31 receptor antagonist) or placebo, alongside background topical corticosteroids (TCS) and/or calcineurin inhibitors (TCI).

Main Findings: At week 16, nemolizumab significantly improved primary outcomes compared to placebo, with a higher proportion achieving clear or almost clear skin (IGA success) and a 75% improvement in Eczema Area and Severity Index (EASI-75). Nemolizumab also showed significant early and sustained improvements in itch and sleep. The safety profile was comparable between groups, with treatment-emergent adverse events occurring in about half of the participants.

Implications for Practice: Nemolizumab, in combination with TCS-TCI, demonstrated robust efficacy in reducing inflammation, itch, and sleep disturbances in moderate-to-severe atopic dermatitis. If approved, it could provide an important addition to current treatment options, particularly for patients inadequately managed by existing therapies.

Reference: Silverberg JI, Wollenberg A, Reich A, et al. (2024). Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials. Lancet, 404(10451), 445-460. DOI: 10.1016/S0140-6736(24)01203-0.

RCT: Oral and topical minoxidil equally effective for male hair loss treatment – JAMA Dermatol

7 May, 2024 | 15:26h | UTC

This study examines the effectiveness, safety, and tolerability of oral minoxidil compared to topical minoxidil in treating male androgenetic alopecia. Conducted as a double-blind, placebo-controlled randomized clinical trial, 90 men aged 18 to 55 with varying degrees of hair loss were recruited and followed for 24 weeks. Participants were divided into two groups: one receiving oral minoxidil 5 mg daily and the other using topical minoxidil 5% twice daily. The primary endpoint was the change in terminal hair density in both the frontal and vertex regions. Results showed that oral minoxidil did not outperform topical minoxidil in terms of increasing hair density on the frontal scalp, though it did show a slight superiority on the vertex area. Common side effects for the oral minoxidil group included hypertrichosis and headaches. Overall, oral minoxidil demonstrated similar efficacy to its topical counterpart and offers an alternative for patients preferring oral treatment or those intolerant to topical formulations.

Reference (link to abstract – $ for full-text):

Mariana Alvares Penha et al. (2024). Oral Minoxidil vs Topical Minoxidil for Male Androgenetic Alopecia A Randomized Clinical Trial. JAMA Dermatology, Published online April 10, 2024. doi:10.1001/jamadermatol.2024.0284

Position Paper | Perioperative antibiotic prophylaxis in skin surgery

3 Aug, 2023 | 13:39h | UTC

Perioperative antibiotic prophylaxis in skin surgery – Position paper of the Antibiotic Stewardship working group of the German Society for Dermatologic Surgery (DGDC) – Journal of the German Society of Dermatology

Part 1: Procedure- and patient-related risk factors

Part 2: Special indications and situations

RCT | Risankizumab outperforms apremilast in moderate plaque psoriasis treatment

3 Aug, 2023 | 13:21h | UTC

Comparison of risankizumab and apremilast for the treatment of adult patients with moderate plaque psoriasis eligible for systemic therapy: results from a randomised, open-label, assessor-blinded phase IV (IMMpulse) study – British Journal of Dermatology

Commentary: Risankizumab Shown to be Superior to Apremilast in Treating Adults with Moderate Psoriasis – HCP Live

European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma

1 Aug, 2023 | 14:24h | UTC

Part 1: Diagnostics and prevention – European Journal of Cancer

Part 2: Treatment – European Journal of Cancer

M-A | Updated evidence supports incisional negative pressure wound therapy for surgical site infection prevention

1 Aug, 2023 | 14:15h | UTC

Incisional negative pressure wound therapy for the prevention of surgical site infection: an up-to-date meta-analysis and trial sequential analysis – eClinicalMedicine

M-A | Oral isotretinoin and triple topical therapies found most effective in acne vulgaris treatment

26 Jul, 2023 | 13:13h | UTC

Comparative Efficacy of Pharmacological Treatments for Acne Vulgaris: A Network Meta-Analysis of 221 Randomized Controlled Trials – Annals of Family Medicine

News Release: Meta-analysis of research on acne reveals that oral isotretinoin, followed by topical antibiotic, benzoyl peroxide and retinoid, are most effective treatments – American Academy of Family Physicians

M-A | Comparison of systemic treatments for chronic plaque psoriasis – Anti-IL17 stands out

25 Jul, 2023 | 13:27h | UTC

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta‐analysis – Cochrane Library

Consensus Paper | Pre and post hair transplantation care

24 Jul, 2023 | 12:46h | UTC

An international expert consensus statement focusing on pre and post hair transplantation care – Journal of Dermatological Treatment

RCT | Direct oral challenge noninferior to skin testing followed by direct oral challenge in low-risk penicillin allergy patients

18 Jul, 2023 | 13:54h | UTC

Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial – JAMA Internal Medicine (free for a limited period)

See also: Visual Abstract

News Release: World-first clinical trial to help millions with penicillin allergies – Vanderbilt University Medical Center

Commentary: Trial supports use of direct oral challenge for penicillin allergy – CIDRAP

Guidelines | Management of atopic dermatitis in adults with topical therapies

14 Jul, 2023 | 12:48h | UTC

Guidelines of care for the management of atopic dermatitis in adults with topical therapies – Journal of the American Academy of Dermatology

News Release: American Academy of Dermatology issues updated guidelines for the management of atopic dermatitis in adults with topical therapies

Phase 2b RCT | Therapeutic ammonia oxidising bacteria B244 shows promising efficacy in atopic dermatitis

11 Jul, 2023 | 13:40h | UTC

Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial – eClinicalMedicine

Consensus Paper | Methotrexate for inflammatory skin disease in pediatric patients

7 Jul, 2023 | 16:16h | UTC

Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines – Pediatrics Dermatology

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis

27 Jun, 2023 | 13:37h | UTC

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis – Annals of the Rheumatic Diseases

Commentary on Twitter

Have you checked the latest recommendations? @eular_org points to consider for the definition of clinical and imaging features suspicious for progression from PsO to PsA

▶️ 3 stages relevant to PsA prevention
▶️ 5 OP and 10 points to consider

? https://t.co/Kr9akTjNC6 pic.twitter.com/cHsg0ZTlb6

— ARD & RMD Open (@ARD_BMJ) June 21, 2023

Summary: Negative pressure wound therapy for treating pressure ulcers – Cochrane Library

RCT | Microdosed incisional clindamycin reduces infection rate in skin cancer surgery

30 May, 2023 | 12:03h | UTC

Effect of Microdoses of Incisional Antibiotics on the Rate of Surgical Site Infections in Skin Cancer Surgery: A Randomized Clinical Trial – JAMA Surgery (link to abstract – $ for full-text)