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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