Algas en la piel...

Adding protothecosis to the protocol

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By Warren R. Heymann, MD, FAAD
April 23, 2025
Vol. 7, No. 16

As a dermatology resident at the outset of the AIDS epidemic, I quickly learned that all bets are off when diagnosing infectious diseases in immunocompromised hosts. That experience taught me to culture broadly for bacterial, atypical mycobacterial, fungal, and viral diseases when suspecting an infectious etiology in an immunosuppressed patient. Rarely (if ever) have I thought about algae — recent publications alerted me to this oversight.

Davies et al. reported the first human infection with a Prototheca alga 60 years ago in a Sierra Leone barefoot rice farmer's foot. Almost 300 cases of human Prototheca infections have been reported since. (1,2) Described in 1894 as a fungus and subsequently reclassified, Prototheca are achlorophyllous saprophytic algae found ubiquitously in soil and water, especially when contaminated by organic waste, as in sewage and ponds. (3) Prototheca infection characteristically presents in three primary forms: cutaneous, olecranon bursitis, and systemic (disseminated) disease. Cutaneous infections commonly arise in immunocompetent patients, while disseminated infections predominantly impact immunocompromised individuals. According to Chen et al., "the prevailing belief is that Prototheca species infect humans either through direct contact with exposed areas or via traumatic inoculation of materials contaminated with the algae." (2) Although there are multiple species of Prototheca, the two main pathogens are Prototheca wickerhamii and Prototheca ciferrii (previously known as P. zopfii genotype 1). (2,3)

Even though patients with cutaneous disease may not be immunosuppressed in the classical sense, mild immune dysregulation may predispose to Prototheca infection. Examples include a 40-year-old man taking methotrexate for reactive arthritis who developed cutaneous protothecosis appearing as a nodule on his finger after washing algae from a freshwater aquarium; a 68-year-old fisherman who practiced canoeing on a dam presented with vesicles at the base of the penis which had evolved over 6 months into an infiltrated and painful erythema throughout the inguinal region. His history of significant obstruction of a prosthesis used to treat an abdominal aortic aneurysm may have caused vascular insufficiency with localized immune dysregulation. (4)

Image from reference 5.

Cutaneous protothecosis is the most common clinical presentation and occurs at sites of penetrating trauma, often localized to the extremities. (5) Chen et al. state, "Protothecosis presents with a heterogeneous, nonspecific array of skin lesions, documented as papules, pustules, plaques, nodules, ulcers, crusts, erosions, and various eczematous, herpetiform, granulomatous, and verrucous lesions." (2) A sporotrichoid pattern may be observed. (3) Histopathologic features of protothecosis demonstrate a mixed inflammatory infiltrate accompanied by necrotizing granulomatous inflammation. The diagnostic endosporulating sporangia (likened to a morula or soccer ball) stains positively with PAS or GMS (Gomori methenamine silver).

Shakoei et al. state, "Disseminated protothecosis is a rare disease in immunocompromised patients but is generally rarer in immunocompetent hosts. Several underlying disorders include immunocompromised patients, prolonged application of steroids, diabetes mellitus, malignancies, organ transplantation, AIDS, and surgeries." In their review of 54 cases of disseminated protothecosis (including their patient) 39 were due to P. wickerhamii, 12 were due to P. zopfii (22.2%), and three were due to Prototheca spp. More men were affected (37 cases, 68.5%) than women (16 cases, 29.6%). The mean age of patients was 39.53 ± 22.48 years, although the age range was from 1-80 years. (6)

The differential diagnosis of prothecosis includes: a) Subcutaneous fungal infections after primary inoculation (e.g., sporotrichosis, cryptococcosis, chromoblastomycosis); b) Nontuberculous Mycobacteria infections (e.g., Mycobacterium marinum, "the fish tank granuloma"); c) Cutaneous candidiasis; d) Unusual cutaneous infectious bacterial agents — (e.g., Erysipelothrix rhusiopathiae [erysipeloid], Serratia marcescens); e) Cutaneous botryomycosis; f) Donovanosis (granuloma inguinale); and g) Neutrophilic dermatoses — (e.g., Behçet's disease, pyoderma gangrenosum). (4)

Image from reference 5.

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The diagnosis may be confirmed by culture (Sabouraud, Mycosel, or blood agar media), although it may be difficult to isolate if overgrown by contaminants. (2,5) PCR and MALDI-TOF mass spectroscopy may identify the organism. (2)

Misdiagnosing protothecosis can delay therapy. In their series of 7 patients, Cullen et al. reported a delay in treatment time that averaged 4 months. (7) There is no standard protocol for treating protothecosis, which may require months of therapy with multiple agents. At-risk patients should be treated aggressively. Surgical excision or debridement is often beneficial for local cutaneous disease. Surgical management is combined with azole antifungals or intravenous amphotericin with a tetracycline for deeper or persistent infections. (5) A novel lipid nanocrystal (LNC) amphotericin B (MAT2203; Matinas Biopharma) is an investigational oral suspension that aims to provide the broad antifungal coverage of conventional amphotericin B with fewer toxicities. It successfully treated a recalcitrant case of protothecosis in a 71-year-old man. (3)

In conclusion, although rare, protothecosis is an underrecognized disorder. Especially in immunocompromised hosts, it should be considered in the differential diagnosis of infectious diseases to avoid misdiagnosis. 

Point to Remember: Protothecosis presents as a localized cutaneous infection, olecranon bursitis, or disseminated disease, especially in immunocompromised patients. Although rare, there have been increasing reports of the disease. Dermatologists should consider this diagnosis in patients presumed to have recalcitrant infectious disorders. 

Our expert's viewpoint

Vitoria Azulay, MD
Institute of Dermatology Professor Rubem David Azulay
Santa Casa de Misericórdia do Rio de Janeiro
Rio de Janeiro, Brazil

Protothecosis: diagnostic challenge of an emerging disease

Protothecosis is a rare algae infection caused by Prototheca spp that may affect both immunocompetent and immunocompromised individuals, although it is more common in the last group. It affects both sexes equally with a predilection for older individuals. Risk factors include immunosuppression, diabetes, organ transplantation, corticosteroid use, and malignancies.

The most commonly involved species is P. wickerhamii, found in in diverse habitats, such as plants, soil, fresh water, and saltwater. Usually its inoculation is caused by trauma.

Clinically, this disease has a range of clinical presentations which may mimic bacterial infections, fungal infections, and eczema, making the diagnosis challenging. Primarily it presents as cutaneous disease, but it can have a rheumatic involvement (bursitis, fasciitis, and most commonly olecranon bursitis).

Treatment of protothecosis lacks established protocols which may difficult disease management. Disseminated infections require treatment with amphotericin B, whereas localized infections are managed with azole antifungals or surgical excision.

1. Davies RR, Spencer H, Wakelin PO., Trans R Soc Trop Med Hyg. 1964 Sep;58:448-51. doi: 10.1016/0035-9203(64)90094-x. PMID: 14206703.

2. Chen Y, Gao A, Ke Y, Zhou X, Lin L, Lu S, Liu Y. Successful Treatment of Cutaneous Protothecosis Due to Prototheca wickerhamii with Terbinafine. Clin Cosmet Investig Dermatol. 2024 Apr 24;17:913-919. doi: 10.2147/CCID.S453620. PMID: 38689756; PMCID: PMC11059624.

3. Pechacek J, Schmitt MM, Ferrè EMN, Webb T, Goldberg J, Pathan S, Banerjee C, Barber P, DiMaggio T, Quinn A, Matkovits T, Castelo-Soccio L, Nussenblatt V, Lionakis MS. Successful Treatment of Refractory Cutaneous Protothecosis With MAT2203, an Oral Lipid Nanocrystal Formulation of Amphotericin B. Open Forum Infect Dis. 2024 Jul 18;11(8):ofae428. doi: 10.1093/ofid/ofae428. PMID: 39091644; PMCID: PMC11292040.

4. Rodrigues FT, Santos PFAM, Soares JVDS, Alves MFGS, Azulay-Abulafia L. Two cases of protothecosis in Brazil: When it is not a bacterial, fungal or viral dermatosis. J Dtsch Dermatol Ges. 2023 Sep;21(9):1022-1024. doi: 10.1111/ddg.15143. Epub 2023 Jul 4. PMID: 37402137.

5. Stephens MR, Aderibigbe O, Steele KT, Elder DE, Glaser L, Jacob J, Rosenbach M. Draining dorsal hand pustules, nodules, and ulcers in a patient with immunosuppression. JAAD Case Rep. 2019 Sep 24;5(10):846-848. doi: 10.1016/j.jdcr.2019.06.016. PMID: 31649969; PMCID: PMC6804474.

6. Shakoei S, Mohamadi F, Ghiasvand F, Khosravi AR, Kamyab K, Salahshour F. Disseminated protothecosis: Case report and review of the literature. J Cutan Pathol. 2024 Sep;51(9):705-713. doi: 10.1111/cup.14668. Epub 2024 Jun 11. PMID: 38863080.

7. Cullen GD, Yetmar ZA, Fida M, Abu Saleh OM. Prototheca Infection: A Descriptive Study. Open Forum Infect Dis. 2023 Jun 6;10(6):ofad294. doi: 10.1093/ofid/ofad294. PMID: 37389225; PMCID: PMC10300632.

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All content found on Dermatology World Insights and Inquiries, including: text, images, video, audio, or other formats, were created for informational purposes only. The content represents the opinions of the authors and should not be interpreted as the official AAD position on any topic addressed. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

Avances en urticaria cronica.

Answered on March 7, 2025

The latest developments in the treatment of chronic spontaneous urticaria (CSU) include several promising therapeutic options beyond the current standard of care. The first-line treatment remains second-generation H1-antihistamines, which can be increased up to fourfold if necessary. For patients who do not respond adequately, omalizumab, an anti-IgE monoclonal antibody, is the next step.[1-2]

Recent advances have focused on targeting specific immune pathways involved in CSU. Bruton's tyrosine kinase (BTK) inhibitors, such as remibrutinib, have shown efficacy by reducing mast cell activation. Dupilumab, which targets the interleukin-4 (IL-4) and IL-13 pathways, is also under investigation and has shown promise in clinical trials. Additionally, ligelizumab, another anti-IgE monoclonal antibody, has demonstrated significant efficacy, although a recent phase III study was discontinued due to nonsuperior clinical impact compared to omalizumab.[1-3]

Other emerging treatments include barzolvolimab, which targets the tyrosine kinase receptor Kit, and therapies targeting the Mas-related G protein-coupled receptor X2 (MRGPRX2). These novel agents offer potential for patients with refractory CSU and may modify the disease course by targeting key immune mechanisms.[1]

Overall, these developments highlight a shift towards more personalized and targeted therapies, aiming to improve outcomes for patients with difficult-to-treat CSU.[1-3] Further research and clinical trials are essential to validate these treatments and integrate them into clinical practice.

Therapies for Chronic Spontaneous Urticaria: Present and Future Developments.

Asero R, Calzari P, Vaienti S, Cugno M.

Pharmaceuticals (Basel, Switzerland). 2024;17(11):1499. doi:10.3390/ph17111499.

New Research

2.

Chronic Urticaria: Unmet Needs, Emerging Drugs, and New Perspectives on Personalised Treatment.

Zuberbier T, Ensina LF, Giménez-Arnau A, et al.

Lancet (London, England). 2024;404(10450):393-404. doi:10.1016/S0140-6736(24)00852-3.

Leading Journal

New Research

3.

Current and Future Management of Chronic Spontaneous Urticaria and Chronic Inducible Urticaria.

Do TT, Canty EA, Joshi SR.

Allergy and Asthma Proceedings. 2023;44(1):3-14. doi:10.2500/aap.2023.44.220093.

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I appreciate many people are working non standard hours. I've sent this email at a time that is convenient to my current working hours, please reply at a time that is convenient to yours.

Finasteride side effects...

Finasteride is associated with several side effects, some of which can be serious. The most common adverse reactions, reported in clinical trials, include decreased libido (1.8%), erectile dysfunction (1.3%), and ejaculation disorder (1.2%). These sexual side effects were more frequent in the first year of treatment and tended to decrease with continued use.[1]

Postmarketing experience has identified additional adverse reactions, including hypersensitivity reactions (such as rash, pruritus, urticaria, and angioedema), persistent sexual dysfunction (including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders), male infertility, testicular pain, hematospermia, male breast cancer, breast tenderness and enlargement, and psychiatric effects (such as depression and suicidal ideation).[1][3]

While some of these side effects, like hypersensitivity reactions and psychiatric effects, can be serious, the incidence of these events is not well-defined due to the voluntary nature of postmarketing reports. It is important to monitor patients for these adverse effects and consider discontinuation of the drug if serious side effects occur.

Recent studies have further elucidated the potential side effects of finasteride, particularly focusing on its psychological and sexual adverse effects. A significant body of evidence has emerged regarding post-finasteride syndrome (PFS), which includes persistent sexual, neurological, and physical side effects that may continue even after discontinuation of the drug. These side effects can be severe and debilitating, affecting a subset of men who are potentially predisposed to these adverse outcomes.[4]

A pharmacovigilance study published in JAMA Dermatology investigated the association between finasteride use and psychological adverse events, including suicidality. The study found a significant disproportionality signal for suicidality (reporting odds ratio [ROR], 1.63; 95% CI, 1.47-1.81) and psychological adverse events (ROR, 4.33; 95% CI, 4.17-4.49) in finasteride users. Younger patients (≤45 years) and those using finasteride for alopecia were particularly at risk. This suggests that younger patients may be more vulnerable to the psychological side effects of finasteride, and these risks should be carefully considered when prescribing the medication.[5]

In summary, while finasteride is effective for treating androgenetic alopecia and benign prostatic hyperplasia, it is associated with serious side effects, including persistent sexual dysfunction and significant psychological adverse events. Clinicians should weigh these risks against the benefits and monitor patients closely for any adverse effects, particularly in younger individuals and those using the drug for hair loss.

1.

PROPECIA. Label via DailyMed.

Food and Drug Administration

Updated date: 2024-10-14

2.

PROPECIA. Label via DailyMed.

Food and Drug Administration

Updated date: 2013-06-11

3.

PROSCAR. Label via DailyMed.

Food and Drug Administration

Updated date: 2024-12-23

4.

Post-Finasteride Syndrome: A Surmountable Challenge for Clinicians.

Traish AM.

Fertility and Sterility. 2020;113(1):21-50. doi:10.1016/j.fertnstert.2019.11.030.

5.

Investigation of Suicidality and Psychological Adverse Events in Patients Treated With Finasteride.

Nguyen DD, Marchese M, Cone EB, et al.

JAMA Dermatology. 2021;157(1):35-42. doi:10.1001/jamadermatol.2020.3385.

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I appreciate many people are working non standard hours. I've sent this email at a time that is convenient to my current working hours, please reply at a time that is convenient to yours.

Antihipertensivos y eczema… diureticos y bloqueadores de canales de calcio hmmm.

Antihypertensive agents and eczema: New data for older patients

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By Warren R. Heymann, MD, FAAD
March 12, 2025
Vol. 7, No. 10

"Anyone who recalls the 1971 Loving Care commercial exclaiming, 'You're not getting older. You're getting better!' is getting older. America is graying — in 2019, people older than 65 years accounted for 16% of the population; in 2040, it is anticipated to be 21.6%. As patients mature, dermatologically, they are at a greater risk of skin cancers, bullous pemphigoid, pruritus, among a myriad of dermatoses. The challenges of comorbidities, polypharmacy, and socioeconomic stresses complicate management." (1) As skin ages, its barrier function deteriorates by becoming dryer due to diminished lipid and water content, predisposing the skin to eczema. (2) Additionally, senescent cutaneous changes presenting as extreme atrophy (aka dermatoporosis, chronic cutaneous fragility syndrome) have a prevalence of 30% in those older than 60 years. (3)

Most older patients with eczematous dermatoses (atopic dermatitis, nummular eczema, stasis dermatitis, seborrheic dermatitis, etc.) will respond to standard therapies such as emollients and topical steroids. Other maneuvers specific to the variant of eczema, such as compression for stasis dermatitis or antifungal shampoos for seborrheic dermatitis, are adjunctive therapies. When routine approaches are inadequate, astute clinicians look carefully at the patient's medication list to determine if any are potential causes. Antihypertensive agents are often considered as culprits. What are the data supporting this hypothesis?

There are scattered individual case reports — a 71-year-old man with a generalized eczematous eruption attributed to the calcium channel blocker (CCB) amlodipine (4) and the report of a 17-year-old man with an eczematous and psoriasiform eruption that developed during long-term therapy with propranolol. (5)

Vena et al. evaluated rashes in 23 hypertensive patients aged 66-87 years; 19 of them were taking another drug in addition to the suspected antihypertensive medication, and 15 were on polytherapy with 3 or more drugs to treat multiple comorbidities. The antihypertensive culprit agents were angiotensin-converting enzyme (ACE) inhibitors in 9 patients, ACE-inhibitors combined with hydrochlorothiazide (HCTZ) in 7 subjects, angiotensin II receptor blockers alone in 2 patients and associated with HCTZ in 5 cases. A generalized eczematous rash was observed in 16 patients and localized eruption in 7 cases, with predominant involvement of lower limbs. Lesions developed after a latency of 4-30 months and were associated with moderate-to-severe itch, that were usually unresponsive to oral antihistamines. Histopathological diagnosis was available for 9 cases, confirming the presence of a spongiotic dermatitis with possible associated psoriasiform skin changes. Complete disappearance of skin lesions after drug discontinuation was considered highly suggestive of the etiological involvement of the suspected drug. Rechallenge resulted in a gradual relapse of eczematous lesions with an average period of 12–16 weeks in 7 cases (3 with ACE-inhibitors, 2 with ACE-inhibitors-HCTZ and 2 with sartans-HCTZ). Of note, 4 other patients, 3 of whom were treated with a dose lower than the original one, did not have any recurrence of their dermatosis. (6)

In a retrospective chart review study of patients with stasis dermatitis (n=43), Gosnell and Nederost demonstrated that patients are more likely to take amlodipine than are basal cell carcinoma patients (n=117) of similar age (19% vs. 5%, P<.02), even when controlled for the use of any antihypertensive medications (25% vs. 10%, P=.05). The authors concluded that amlodipine therapy is associated with stasis dermatitis and discontinuing amlodipine should be considered when stasis dermatitis is diagnosed. (7)

Joly et al. evaluated drugs associated with eczematous eruptions in patients older than 60 years by conducting a case–control study on 102 cases and 204 controls. There was an association between CCB and eczema, with a matched odds ratio (OR) of 2.5. To ascertain the course of patients after CCB withdrawal, two ancillary studies were performed on 74 patients with eczematous eruptions from their department before the case–control study period and on 101 patients registered in the French ''Pharmacovigilance'' database. Healing of these eruptions after CCB withdrawal occurred in 83 and 68% of these cases, respectively. The authors concluded that long-term use of CCB is a risk factor for chronic eczematous eruptions of the elderly. (8)

Summers et al performed a retrospective case-control study of 94 patients 50 years and older presenting with otherwise unexplainable symmetrical eczematous eruptions of at least 2 months duration. Inclusion criteria also included histopathologic changes of spongiotic and/or interface dermatitis and clinical suspicion of a drug-induced cutaneous eruption. The controls comprised 132 age-, sex-, and race-matched patients presenting with benign dermatologic conditions. A statistically significant difference in drug class use between cases and controls for CCB and thiazides was noted. For CCB and thiazides, the matched OR were 4.21 and 2.07, respectively. The histopathological pattern subgroup analysis failed to show any statistically significant association. (9)

Ye et al. completed a longitudinal cohort study of a population-based sample of individuals 60 years and older without a baseline diagnosis of eczematous dermatitis. Subsequently, new active eczematous dermatitis was based on the first date of 1 of the 5 most common eczema codes. Among the total study sample of 1,561,358 older adults (mean age, 67 years; 54% female), the overall prevalence of eczematous dermatitis was 6.7% during a median follow-up duration of 6 years. Eczematous dermatitis incidence was higher among participants receiving antihypertensive drugs than those who did not (12 vs 9 of 1000 person-years of follow-up). Adjusted Cox proportional hazard models found that participants who received any antihypertensive drugs had a hazard ratio [HR] of 1.29. When assessing each antihypertensive drug class individually, the largest effect size was observed for diuretic drugs (HR, 1.21) and CCB (HR, 1.16); the smallest effect sizes were for ACE inhibitors (HR, 1.02) and β-blockers (HR, 1.04). The authors concluded that antihypertensive drugs are associated with a small increased rate of eczematous dermatitis, with effect sizes largest for CCB and diuretic drugs and smallest for ACE inhibitors and β-blockers. (10)

These findings raise many interesting questions about how antihypertensive agents contribute to eczematous dermatoses in the elderly. Draelos et al. state "Many senescent cells develop a senescent-associated secretory phenotype, leading to the secretion of a very large number of pro-inflammatory factors, such as cytokines and chemokines, as well as factors that promote tissue dysfunction, including proteases, extracellular vesicles, metabolites and lipids." (3) Each category of antihypertensive drugs could affect this background milieu by different pathomechanisms yet to be defined. Practically, I agree with the "meaning" of Ye et al. that clinicians "should consider antihypertensive treatment as part of the differential diagnoses for older patients presenting with eczematous dermatitis." (10)

Point to Remember: Antihypertensive agents, especially diuretics and calcium channel blockers, may cause eczematous dermatoses in older patients. 

Our expert's viewpoint

Katrina Abuabara, MD, MA, MSCE, FAAD
Associate Professor of Dermatology, UCSF
Associate Adjunct Professor of Epidemiology, UC Berkeley School of Public Health 

In many cases, the diagnosis of eczematous dermatitis is straightforward. For example, most children presenting with flexural lesions and a family history of atopic disease could easily be classified as having atopic dermatitis. However, we lack specific diagnostic tests for eczematous dermatoses and even atopic dermatitis among children is clinically heterogeneous. According to Hanifin and Rajka, the diagnosis requires the presence of at least three of four major criteria and three of 23 minor criteria. Molecular studies show that the underlying phenotype is likely to vary between individuals and within individuals over time. The picture becomes even more complicated among older adults with eczematous dermatitis who can present with a variety of clinical features. It is important to rule out exclusionary conditions like scabies, contact dermatitis, cutaneous lymphoma, and to consider a drug-induced dermatitis. This task can be challenging for even the most astute clinician because most older adults take multiple medications, skin symptoms may appear months after initiation of the offending drug and take months to clear after drug discontinuation. Therefore, data about the drugs most likely to be implicated are important for clinicians. 

In our population-based study (10) we were surprised to find an association between multiple antihypertensive classes and eczematous dermatitis. Some associations, while statistically significant because we were using a very large database, are unlikely to be clinically meaningful. Moreover, it is possible that in instances where the effect sizes were small, the association is explained by an underlying association between eczematous dermatitis and hypertension or other shared risk factors that we were not able to fully adjust for. In either case, additional research is needed into the potential mechanisms underlying an association. 

Given the weight of available evidence, it is reasonable to consider switching antihypertensive classes for patients with eczematous dermatitis on CCBs and diuretic drugs. However, this should be done in the context of response to treatment given that eczematous dermatitis may also be effectively managed with topical therapies or phototherapy. 

1. Heymann WR. Geriatric dermatology: Grow old along with me! J Am Acad Dermatol. 2022 May;86(5):1000-1001. doi: 10.1016/j.jaad.2022.02.046. Epub 2022 Mar 1. PMID: 35245564.

2. Nazarko L. Eczema and the older person. Br J Community Nurs. 2020 Sep 2;25(9):451-459. doi: 10.12968/bjcn.2020.25.9.451. PMID: 32881612.

3. Draelos Z, Bogdanowicz P, Saurat JH. Top weapons in skin aging and actives to target the consequences of skin cell senescence. J Eur Acad Dermatol Venereol. 2024 Jul;38 Suppl 4:15-22. doi: 10.1111/jdv.19648. PMID: 38881445.

4. Yoo J, Jue MS. Intractable pruritus with chronic eczema in an elderly patient caused by long-term intake of calcium channel blocker. Contact Dermatitis. 2017 Nov;77(5):339-340. doi: 10.1111/cod.12832. PMID: 29063690.

5. Faure M, Hermier C, Perrot H. Accidents cutanés provoqués par le propranolol [Cutaneous reactions to propranolol (author's transl)]. Ann Dermatol Venereol. 1979 Feb;106(2):161-5. French. PMID: 38730.

6. Vena GA, Cassano N, Coco V, De Simone C. Eczematous reactions due to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Immunopharmacol Immunotoxicol. 2013 Jun;35(3):447-50. doi: 10.3109/08923973.2013.797992. PMID: 23672527.

7. Gosnell AL, Nedorost ST. Stasis dermatitis as a complication of amlodipine therapy. J Drugs Dermatol. 2009 Feb;8(2):135-7. PMID: 19213228.

8. Joly P, Benoit-Corven C, Baricault S, Lambert A, Hellot MF, Josset V, Barbaud A, Courville P, Delaporte E, Collet E, Carvalho P, Modeste-Duval AB, Lacour JP, L'Anthoën-Arditi MH, Thuillez C, Benichou J. Chronic eczematous eruptions of the elderly are associated with chronic exposure to calcium channel blockers: results from a case-control study. J Invest Dermatol. 2007 Dec;127(12):2766-71. doi: 10.1038/sj.jid.5701018. Epub 2007 Aug 23. PMID: 17713574.

9. Summers EM, Bingham CS, Dahle KW, Sweeney C, Ying J, Sontheimer RD. Chronic eczematous eruptions in the aging: further support for an association with exposure to calcium channel blockers. JAMA Dermatol. 2013 Jul;149(7):814-8. doi: 10.1001/jamadermatol.2013.511. PMID: 23636109.

10. Ye M, Chan LN, Douglas I, Margolis DJ, Langan SM, Abuabara K. Antihypertensive Medications and Eczematous Dermatitis in Older Adults. JAMA Dermatol. 2024 Jul 1;160(7):710-716. doi: 10.1001/jamadermatol.2024.1230. PMID: 38776099; PMCID: PMC11112493.

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All content found on Dermatology World Insights and Inquiries, including: text, images, video, audio, or other formats, were created for informational purposes only. The content represents the opinions of the authors and should not be interpreted as the official AAD position on any topic addressed. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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a mobile device.

What is the best treatment for androgenetic alopecia?

The best treatment for androgenetic alopecia (AGA) involves a combination of pharmacological and non-pharmacological approaches, tailored to the patient's gender and specific needs. For male patients, the most effective treatments with the highest level of evidence are oral finasteride and topical minoxidil. Finasteride, a 5-alpha reductase inhibitor, is FDA-approved for male AGA and has been shown to be effective in improving hair density and slowing hair loss.[1][2][3] Minoxidil, available in 2% and 5% topical formulations, is also FDA-approved and effective for both men and women, promoting hair growth and increasing hair density.[2][3][4]

For female patients, topical minoxidil remains the primary treatment option with strong evidence supporting its efficacy and safety.[3] While finasteride is not typically used in women due to potential teratogenic effects, some studies suggest its use in postmenopausal women under careful supervision.[5]

Low-level laser therapy (LLLT) is another FDA-cleared option for both men and women, with evidence supporting its efficacy in promoting hair growth.[2][4][6] Platelet-rich plasma (PRP) therapy has also shown promise in some studies, although the evidence is less robust and more variable.[4]

Emerging treatments, such as dutasteride, have shown potential, particularly in men, but are not yet FDA-approved for AGA. Dutasteride may offer superior efficacy compared to finasteride, especially in the frontal scalp area, but concerns about side effects remain.[1][4]

Overall, the choice of treatment should be individualized, considering the patient's gender, the severity of hair loss, and potential side effects. Regular follow-up is essential to assess treatment efficacy and adjust the therapeutic approach as needed.

References
[1] Saceda-Corralo D, Domínguez-Santas M, Vañó-Galván S, Grimalt R. What's New in Therapy for Male Androgenetic Alopecia?. American Journal of Clinical Dermatology. 2023;24(1):15-24. doi:10.1007/s40257-022-00730-y.
[2] Adil A, Godwin M. The Effectiveness of Treatments for Androgenetic Alopecia: A Systematic Review and Meta-Analysis. Journal of the American Academy of Dermatology. 2017;77(1):136-141.e5. doi:10.1016/j.jaad.2017.02.054.
[3] Varothai S, Bergfeld WF. Androgenetic Alopecia: An Evidence-Based Treatment Update. American Journal of Clinical Dermatology. 2014;15(3):217-30. doi:10.1007/s40257-014-0077-5.
[4] Gupta AK, Mays RR, Dotzert MS, et al. Efficacy of Non-Surgical Treatments for Androgenetic Alopecia: A Systematic Review and Network Meta-Analysis. Journal of the European Academy of Dermatology and Venereology : JEADV. 2018;32(12):2112-2125. doi:10.1111/jdv.15081.
[5] Kelly Y, Blanco A, Tosti A. Androgenetic Alopecia: An Update of Treatment Options. Drugs. 2016;76(14):1349-64. doi:10.1007/s40265-016-0629-5.
[6] Lama SBC, Pérez-González LA, Kosoglu MA, Dennis R, Ortega-Quijano D. Physical Treatments and Therapies for Androgenetic Alopecia. Journal of Clinical Medicine. 2024;13(15):4534. doi:10.3390/jcm13154534.


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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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FFA componente genetico

Brief Report 

February 12, 2025

Epistasis of ERAP1 With 4 Major Histocompatibility Complex Class I Alleles in Frontal Fibrosing AlopeciaA Genome-Wide Association Study Meta-Analysis

Tuntas Rayinda, MD, MSc, PhD^1,2; Nick Dand, PhD³; Sheila M. McSweeney, MB, MSc¹; et alEvangelos Christou, MD¹; Chuin Ying Ung, MBBS, PhD¹; Catherine M. Stefanato, MD¹; David A. Fenton, MBChB¹; Matthew Harries, MBChB, PhD^4,5; Ioulios Palamaras, MD, PhD⁶; Alice Tidman, BSc, MBChB⁷; Susan Holmes, BSc(Hons), MBChB, MD⁷; Anastasia Koutalopoulou, MD⁸; Michael Ardern-Jones, BSc, MBBS, DPhil⁸; Manjit Kaur, BMedSci(Hons), BMBS⁹; Sofia Papanikou, MD, MSc¹⁰; Vasiliki Chasapi, MD, PhD¹⁰; Sergio Vañó-Galvan, MD, PhD¹¹; David Saceda-Corralo, MD, PhD¹¹; Ana Melián-Olivera, MD¹¹; Carlos Azcarraga-Llobet, MD¹¹; Alejandro Lobato-Berezo, MD¹²; Mariona Bustamante, PhD¹³; Jordi Sunyer, MD, PhD¹³; Michela Valeria Rita Starace, MD, PhD^14,15; Bianca Maria Piraccini, MD, PhD^14,15; Isabel Pupo Wiss, BA¹⁶; Maryanne Makredes Senna, MD¹⁶; Rashmi Singh, MD¹⁷; Kathrin Hillmann, MD¹⁷; Varvara Kanti-Schmidt, MD^17,18; Ulrike Blume-Peytavi, MD, PhD¹⁷; John A. McGrath, MBBS, MD¹; Michael A. Simpson, PhD³; Christos Tziotzios, MA, MB, BChir(Cantab), PhD¹¹

Author Affiliations

JAMA Dermatol. Published online February 12, 2025. doi:10.1001/jamadermatol.2024.6434

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Key Points

Question  Is there any novel genetic variation contributing to the risk of frontal fibrosing alopecia (FFA)?

Findings  In this meta-analysis of 4 FFA cohorts including 1585 female individuals with FFA and 5083 controls, there was genome-wide significant evidence of an association at a new locus at 5q15. Within the major histocompatibility complex (MHC) class I region, stepwise conditional association analyses revealed independent associations for 4 classical MHC class I alleles (HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01), and there was a statistical interaction between the MHC class I allele and the lead variant at 5q15.

Meaning  These findings highlight synergistic genetic associations with FFA susceptibility via peptide processing and antigen presentation pathways and highlight potential relevance of endoplasmic reticulum aminopeptidase–mediated therapeutic targets.

Abstract

Importance  Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets.

Objective  To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci.

Design, Setting, and Participants  Four genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 (ERAP1) loci.

Main Outcomes and Measures  Genome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci.

Results  Of 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5′ untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10⁻⁸). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles.

Conclusions and Relevance  In this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.

• Editorial
  Clinical Implications of Genetic Discoveries on Frontal Fibrosing Alopecia
  JAMA Dermatology

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

Please excuse the shortness of this message, as it has been sent from
a mobile device.

Que hacer si sus labios están secos...

While it may seem that dry, cracked lips are something you must live with until spring comes, you can have soft, supple lips year-round. Here's what dermatologists recommend.

1. Use non-irritating lip balm, lipstick, and other products that you apply to your lips. Many people mistake discomfort, such as burning, stinging, or tingling, as a sign that the active ingredients in a product are working. That's not what's happening. You're actually irritating your lips, so you want to stop using any product that irritates your lips.

Ingredients to avoid while your lips are chapped: To help chapped lips heal, stop applying lip products that contain any of the following:

   • Camphor
   • Eucalyptus
   • Flavoring: Cinnamon, citrus, mint, and peppermint flavors can be especially irritating to dry, chapped lips
   • Fragrance
   • Lanolin
   • Menthol
   • Octinoxate or oxybenzone
   • Phenol (or phenyl)
   • Propyl gallate
   • Salicylic acid
   Ingredients that can help heal chapped lips: While some ingredients can irritate dry, cracked lips, others can help them heal. When looking for products to use on your chapped lips, dermatologists recommend ones that contain one or more of the following:


   • Castor seed oil
   • Ceramides
   • Dimethicone
   • Hemp seed oil
   • Mineral oil
   • Petrolatum
   • Shea butter
   • Sun-protective ingredients, such as titanium oxide or zinc oxide
   • White petroleum jelly
   It also helps to use products that are fragrance free and hypoallergenic.

   If your lips burn, sting, or feel uncomfortable when you apply a product to your lips, it means you're irritating your lips, so you want to stop using that product.

   

2. Apply a non-irritating lip balm (or lip moisturizer) several times a day and before bed. If your lips are very dry and cracked, try a thick ointment, such as white petroleum jelly. Ointment seals in water longer than waxes or oils.

3. Slather on a non-irritating lip balm with SPF 30 or higher before going outdoors. Even in the winter, it's important to protect your lips from the sun. The sun can burn dry, chapped lips more easily, which could trigger cold sores.

To protect dry, chapped lips from the sun, use lip balm that contains offers SPF 30 or higher and one (or both) of these sun-protective ingredients:


   • Titanium oxide
   • Zinc oxide
   While outdoors, apply the lip balm every 2 hours.

4. Drink plenty of water. Chapped lips are dry lips, so you want to stay hydrated.

5. Stop licking, biting, and picking at your lips. When lips feel dry, it may feel natural to wet them by licking them, but this can worsen the problem. As saliva evaporates, your lips become drier.

Picking or biting your lips also irritates them, which can prevent healing.

   Lip licking can be a hard habit to break. When you catch yourself licking your lips, try applying a non-irritating lip balm instead.

   

6. Avoid holding items made of metal with your lips. Paperclips, jewelry, and other everyday products made of metal can irritate your already sensitive lips.

7. Plug in a humidifier at home. A humidifier in your bedroom can be especially helpful, especially if you breathe through your mouth at night.

By following these dermatologists' tips for chapped lips, you should have noticeable improvement in 2 to 3 weeks. To prevent your lips from chapping again, continue applying lip balm whenever it's dry indoors or outside.

When to see a dermatologist?

Most of the time, the above self-care can heal dry, chapped lips in 2 to 3 weeks. If it doesn't, see a board-certified dermatologist.

Your chapped lips could be caused by something aside from dry weather. An allergic reaction, yeast infection, or something more serious can make your lips feel dry and uncomfortable. Actinic cheilitis is a precancerous condition that turns one or both lips dry and scaly. A board-certified dermatologist can diagnose the cause.

https://nature.proxyucr.elogim.com/articles/d41586-024-04068-9

The skin's 'surprise' power: it has its very own immune system

The finding could lead to the development of needle-free vaccines.

13 December 2024

Skin can generate antibodies, independent of the rest of the immune system.Credit: kazuma seki/Getty

The skin — once thought to be a mainly passive barrier — can produce its own antibodies that fight off infections, a pair of studies reports in Nature this week^1,2. The findings could pave the way for the development of needle-free vaccines that can be applied to the skin.

Although scientists have previously seen immune responses in the skin during infections, finding similar reactions in healthy skin is "a surprise", says Daniel Kaplan, a dermatologist and immunologist at the University of Pittsburgh in Pennsylvania. "The idea of a semi-autonomous immune system in a peripheral tissue is very exciting," he says.

Dual role

The immune system has to fight off harmful pathogens without attacking the helpful microorganisms that inhabit the body. Previous research showed³ that the skin of adult mice that had been raised without microbes could be colonized by Staphylococcus epidermidis, a common and harmless bacterium found on human skin. This long-term colonization triggered the production of specific immune cells, called T cells, which helped to strengthen local immunity.

"The next and maybe main chapter in this saga is that the response to this ubiquitous skin colonist is much more potent than we had realized," says Michael Fischbach, a microbiologist at Stanford University in California, who was a co-author on both of the latest studies.

"When the immune system sees a friendly bacterium, you would think that it would just give a friendly wave and walk in the other direction, but that's not at all what happens," he says.

In experiments with mice, mucosal immunologist Inta Gribonika at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and her colleagues discovered that S. epidermidis triggers the activation of B cells, the immune cells necessary to produce antibodies¹. The skin then made antibodies against S. epidermidis; these persisted for at least 200 days and could form without previous exposure to other microbes.

The skin was able to generate this immune response even when lymph nodes — the immune hubs that help to activate immune cells — were disabled. The presence of S. epidermidis also induced the formation of specialized immune structures in the skin that attract T and B cells, boosting the production of antibodies.

Immune memory

Vaccines work by teaching the immune system — which includes T and B cells, along with antibodies — to recognize and remember a pathogen, so the body can respond quickly if exposed again.

Building on this idea, the team explored whether they could redirect the immune response triggered by the harmless S. epidermidis to target pathogens, to develop a new type of vaccine.

In a second study², Fischbach and his team showed that S. epidermidis triggers an antibody response resembling that seen in conventional vaccines.

By modifying S. epidermidis to display foreign proteins — such as part of the tetanus toxin — on its surface, the researchers were able to induce immune responses in the mice's bloodstream and in mucous membranes such as the lining of the nose. These responses protected the animals when they were given a lethal dose of the toxin.

Mucosal vaccines

Fischbach's work is part of a growing interest in developing vaccines that induce antibodies in mucosal areas. This type of protection could help to stop respiratory or other infections before they start and reduce the spread of disease.

Another advantage over conventional vaccines is that engineered S. epidermidis could be added to a cream and simply applied to the skin. Such a vaccine, Fischbach says, would be cheap to produce and easy to distribute. Furthermore, it would not have to be administered by health-care worker, making it especially useful in under-served regions of the world.

The idea of using the immune response from S. epidermidis in the skin to develop therapies "is really out there", says Thomas Kupper, a skin immunologist at Harvard Medical School in Boston, Massachusetts. "It is a super-creative application of these findings."

But Kupper adds that it's still unclear whether the skin's response to S. epidermidis is as strong in people as it is in mice. Fischbach notes that early data suggest healthy people have high levels of antibodies against S. epidermidis. But before this approach can be used in people, it must first be proved safe and effective in non-human primates and in humans, following the usual process for developing medicines, he says. "If this is going to be deployed in the real world, we have to show that it works."

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

Please excuse the shortness of this message, as it has been sent from
a mobile device.