European Journal of Cardiovascular Medicine

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that significantly affects quality of life. It is characterized by pruritic, eczematous lesions and is frequently associated with allergic comorbidities such as asthma and allergic rhinitis. The prevalence of AD has increased globally in recent decades, affecting up to 20% of children and 3% of adults, thereby imposing a considerable burden on patients and healthcare systems [1]. The condition often persists into adulthood or recurs intermittently, underscoring the need for effective and sustainable long-term management strategies [2].

Topical corticosteroids (TCS) have been the cornerstone of AD treatment for more than five decades. Their anti-inflammatory and immunosuppressive effects make them highly effective for controlling acute flares and maintaining remission [3]. However, concerns regarding adverse effects such as cutaneous atrophy, striae, telangiectasia, and hypothalamic–pituitary–adrenal axis suppression have led to cautious prescribing, especially in sensitive areas like the face and intertriginous regions [4]. Moreover, widespread concerns about “steroid phobia” among patients and caregivers frequently result in poor adherence, which compromises treatment outcomes [5].

Topical calcineurin inhibitors (TCIs), such as tacrolimus and pimecrolimus, emerged as non-steroidal alternatives designed to address the limitations of corticosteroids. These agents inhibit calcineurin-dependent T-cell activation, thereby reducing the release of pro-inflammatory cytokines. Unlike TCS, they do not cause skin atrophy, making them particularly useful for long-term use and application to delicate anatomical sites [6]. Clinical trials have demonstrated that TCIs are effective in both children and adults, with good tolerability even during prolonged use [7]. Proactive regimens with tacrolimus have been shown to reduce relapse frequency, improve disease control, and enhance patient-reported quality of life [8].

Despite their benefits, TCIs are not without limitations. Application-site burning or stinging is commonly reported, and questions regarding long-term safety, particularly the potential risk of malignancies, have generated debate, although definitive evidence remains lacking [9]. Additionally, TCIs are more costly compared to TCS, which can restrict their accessibility in resource-limited healthcare settings [10].

The comparative effectiveness and safety of TCS versus TCIs have been investigated in various trials, but results remain inconsistent. While some studies suggest superiority of TCIs in preventing relapses and managing sensitive skin areas, others support the established efficacy, affordability, and accessibility of TCS in routine practice. Moreover, patient adherence, satisfaction, and preference may vary between the two therapeutic classes, influenced by perceptions of safety, tolerability, and convenience.

Given the persistent uncertainties and the scarcity of data from South Asian populations, further comparative research is essential. This study was therefore conducted to evaluate the long-term efficacy, safety, treatment adherence, and satisfaction between TCS and TCIs in patients with moderate AD.

This comparative observational study was conducted in the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from July 2010 to June 2011. A total of 60 patients diagnosed with atopic dermatitis (AD) were enrolled and equally allocated into two groups: the topical corticosteroid (TCS) group (n = 30) and the topical calcineurin inhibitor (TCI) group (n = 30).

Sample Selection

Inclusion Criteria:

• Patients aged 18 years and above.
• Diagnosed with moderate atopic dermatitis (EASI >10).
• History of at least one episode of AD in the past year.
• Provided informed written consent.

Exclusion Criteria:

• Patients with severe systemic illness or immunodeficiency.
• Presence of active skin infection at baseline.
• Prior systemic corticosteroid or immunosuppressive therapy within 4 weeks.
• Pregnant or lactating women.

Data Collection and Study Procedure: Data were collected using structured case record forms. Baseline demographic and clinical characteristics were recorded, including disease duration, previous treatments, and severity scores. Clinical efficacy was evaluated using the Eczema Area and Severity Index (EASI) and Investigator Global Assessment (IGA). Safety assessments included monitoring for local and systemic adverse events. Adherence was measured through patient self-reporting and follow-up visits. Data analysis was conducted using SPSS version 17.0. Descriptive statistics, including mean and standard deviation for continuous variables and frequencies with percentages for categorical variables, were used. Between-group comparisons were performed using the independent t-test for continuous variables and the chi-square test for categorical variables. A p-value ≤0.05 was considered statistically significant. All participants provided informed consent. Confidentiality and anonymity were strictly maintained throughout the study.a

Table 1: Baseline Characteristics of Participants (n = 60)

Table 1 shows baseline characteristics of participants in both treatment groups. Mean age was similar between TCS (28.4 ± 7.5 years) and TCI (29.1 ± 8.2 years) groups. Gender distribution was balanced, with 53.3% males in the TCS and 50% in the TCI groups. The proportion of patients with moderate AD was comparable (73.3% vs. 76.7%), as were disease duration (4.2 vs. 4.5 years) and prior topical therapy use. No significant differences were observed in baseline parameters.

Table 2: Clinical Efficacy Outcomes at 6 Months

Table 2 presents clinical efficacy outcomes at 6 months. Mean EASI reduction was slightly greater in the TCI group (72.5% ± 11.0) compared to TCS (68.0% ± 12.5), though not statistically significant. More patients achieved ≥75% improvement in the TCI group (76.7% vs. 66.7%). Similarly, more participants achieved an Investigator Global Assessment score ≤1 (70.0% vs. 63.3%) and treatment success (73.3% vs. 66.7%). These differences were not statistically significant.

Table 3: Safety and Adverse Events during 6 Months

Table 3 describes safety and adverse events during treatment. Application-site burning was more frequent in the TCI group (26.7%) compared to TCS (10.0%), though not statistically significant. Skin atrophy occurred in 6.7% of TCS patients but was absent in the TCI group. Pruritus or irritation was reported in both groups, with slightly higher rates in TCI (23.3% vs. 16.7%). One patient from each group discontinued therapy due to adverse events.

Table 4: Treatment Adherence & Satisfaction (6 Months)

Table 4 shows the treatment adherence and satisfaction outcomes. Adherence rates were high in both groups, slightly higher in TCI (84.5% vs. 82.0%). Patient satisfaction was also higher in TCI (76.7% vs. 70.0%). Preference for continuing therapy was reported by 80.0% in TCI compared to 66.7% in TCS. No significant differences were observed between groups in adherence or satisfaction.

This study evaluated the comparative outcomes of topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) in the long-term management of moderate atopic dermatitis (AD). The results demonstrated that both therapeutic groups achieved significant clinical improvement, with no statistically significant differences in efficacy, adherence, or patient satisfaction, although minor variations in adverse events were observed.

Both groups showed substantial reductions in disease severity, as indicated by EASI scores and Investigator Global Assessment (IGA) outcomes. The TCI group had slightly higher rates of treatment success, but these differences did not reach statistical significance. This finding supports previous evidence suggesting comparable efficacy between the two treatment modalities. Reitamo et al. reported that long-term tacrolimus use provided sustained efficacy similar to corticosteroids [11], while Neumann et al. also found no clear superiority of one treatment over the other in terms of long-term disease control [12]. Likewise, Hanifin et al. demonstrated that tacrolimus ointment maintained efficacy for up to four years, supporting its role as a reliable long-term option [13].

The safety profiles of the two therapies reflected their known pharmacological properties. Application-site burning was more frequently reported in the TCI group, consistent with earlier findings by Remitz et al., who identified local irritation as the most common TCI-related adverse event [14]. Conversely, skin atrophy was observed only in the TCS group, which aligns with the well-established steroid-associated risk profile [15]. These observations highlight the trade-off between the two therapies: corticosteroids may cause structural skin changes with prolonged use, while TCIs are associated with transient local intolerance. Nonetheless, both treatments were generally well tolerated, with only one discontinuation in each group, underscoring their overall safety.

Adherence and satisfaction rates were high in both groups, with marginally higher adherence and willingness to continue therapy in the TCI group. This may reflect patient perceptions regarding steroid safety, particularly in light of the phenomenon of “steroid phobia.” Charman and Williams emphasized that negative perceptions of corticosteroids frequently undermine adherence in AD management [16]. Staab et al. similarly reported improved caregiver satisfaction with TCI therapy in children, highlighting the impact of safety perceptions on treatment preference [17].

The lack of significant efficacy differences brings cost considerations into focus. TCS are inexpensive, widely available, and highly effective, making them a practical choice in most healthcare systems. TCIs, while effective, are significantly more expensive and less accessible in resource-limited settings. Green et al. noted that once-daily corticosteroid regimens are not only effective but also economically advantageous [3]. For many patients, particularly in low- and middle-income countries, this cost disparity may limit the routine use of TCIs despite their favorable safety profile.

Long-term safety concerns regarding TCIs have been a matter of debate. The FDA’s black-box warning raised questions about potential malignancy risk, though evidence to date has not confirmed such associations. Naylor et al. found no increased incidence of non-melanoma skin cancers among patients treated with tacrolimus [18], and Spergel and Leung also concluded that TCIs remain safe when used as indicated [19]. These findings, coupled with the observation of no systemic adverse events during six months of therapy, add reassurance regarding their safety in clinical practice.

The role of TCIs in proactive management is another important consideration. Proactive therapy with tacrolimus has been shown to reduce relapse rates and extend remission periods. Thaçi et al. reported that intermittent use of tacrolimus on previously affected areas significantly improved long-term disease control [20]. While this study did not include a proactive protocol, the favorable patient satisfaction and adherence trends observed in the TCI group suggest that such strategies could be beneficial.

Finally, the results resonate with those of Bieber et al., who demonstrated comparable efficacy between tacrolimus and corticosteroids in children with acute flares, reinforcing the view that both drug classes remain valuable in different clinical contexts [21]. Together, these findings emphasize that treatment choice should not hinge on efficacy alone but rather consider safety, tolerability, patient preference, and cost-effectiveness.

This study contributes region-specific data from Bangladesh, where real-world comparative evidence remains limited. However, it is constrained by a relatively small sample size, a single-center design, and a follow-up period limited to six months. These limitations preclude definitive conclusions regarding long-term safety outcomes, particularly rare adverse events. Larger, multicenter studies with extended follow-up are warranted to confirm these findings and inform evidence-based guidelines tailored to resource-limited settings.

In summary, both TCS and TCIs are effective and safe for the long-term management of moderate AD. TCIs may offer advantages in terms of patient satisfaction and avoidance of steroid-related side effects, but their higher cost limits widespread use. Treatment decisions should be individualized, balancing efficacy, safety, cost, and patient preferences to optimize long-term outcomes in atopic dermatitis.

Limitations of the study

The study was limited by its relatively small sample size and six-month follow-up period, which may not fully capture rare or long-term adverse events. Additionally, the single-center design may reduce the generalizability of findings to other populations.

This study showed that topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) are effective and safe for long-term management of moderate atopic dermatitis. Both groups exhibited significant clinical improvement, with no significant differences in efficacy, adherence, or satisfaction. TCIs had fewer steroid-related adverse effects, like skin atrophy, though application-site burning was more common. While TCS remains cost-effective and accessible, TCIs may be preferable for sensitive skin areas or patients concerned about steroid safety. Individualized treatment considering efficacy, safety, cost, and patient preference is recommended for optimal outcomes.

Acknowledgment

I would like to express my sincere gratitude for the invaluable support and cooperation provided by the staff, participants, and my co-authors/colleagues who contributed to this study.

Conflicts of interest

There are no conflicts of interest.

1. Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR, of Asthma IS. Is eczema really on the increase worldwide?. Journal of Allergy and Clinical Immunology. 2008 Apr 1;121(4):947-54.
2. Leung AK, Barber KA. Managing childhood atopic dermatitis. Advances in therapy. 2003 May;20(3):129-37.
3. Green C, Colquitt JL, Kirby J, Davidson P. Topical corticosteroids for atopic eczema: clinical and cost effectiveness of once‐daily vs. more frequent use. British journal of dermatology. 2005 Jan 1;152(1):130-41.
4. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. Journal of the American Academy of Dermatology. 2006 Jan 1;54(1):1-5.
5. Charman CR, Morris AD, Williams HC. Topical corticosteroid phobia in patients with atopic eczema. British journal of dermatology. 2000 May 1;142(5):931-6.
6. Meurer M, Wozel G. The treatment of atopic dermatitis in adults with topical calcineurin inhibitors. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und Verwandte Gebiete. 2003 Apr 4;54(5):424-31.
7. Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. Bmj. 2005 Mar 3;330(7490):516.
8. Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E, Giannetti A, Bieber T, Vyas J, Deleuran M, European Tacrolimus Ointment Study Group. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy. 2008 Jun;63(6):742-50.
9. Berger TG, Duvic M, Van Voorhees AS, Frieden IJ. The use of topical calcineurin inhibitors in dermatology: safety concerns: report of the American Academy of Dermatology Association Task Force. Journal of the American Academy of Dermatology. 2006 May 1;54(5):818-23.
10. Thomas KS, Armstrong S, Avery A, Po AL, O'Neill C, Young S, Williams HC. Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema. Bmj. 2002 Mar 30;324(7340):768.
11. Reitamo S, Rustin M, Harper J, Kalimo K, Rubins A, Cambazard F, Brenninkmeijer EE, Smith C, Berth‐Jones J, Ruzicka T, Sharpe G. A 4‐year follow‐up study of atopic dermatitis therapy with 0· 1% tacrolimus ointment in children and adult patients. British Journal of Dermatology. 2008 Oct 1;159(4):942-51.
12. Neumann E, Amtage D, Bruckner‐Tuderman L, Mockenhaupt M. A single‐center open‐label long‐term comparison of tacrolimus ointment and topical corticosteroids for treatment of atopic dermatitis. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2008 Jul;6(7):548-53.
13. Hanifin JM, Paller AS, Eichenfield L, Clark RA, Korman N, Weinstein G, Caro I, Jaracz E, Rico MJ, US Tacrolimus Ointment Study Group. Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. Journal of the American Academy of Dermatology. 2005 Aug 1;53(2):S186-94.
14. Remitz A, Harper J, Rustin M, Goldschmidt WF, Palatsi R, van der Valk PG, Sharpe G, Smith CH, Dobozy A, Turjanmaa K, European Tacrolimus Ointment Study Group. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. Acta dermato-venereologica. 2007;87(1):54-61.
15. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. Journal of the American Academy of Dermatology. 2006 Jan 1;54(1):1-5.
16. Charman C, Williams H. The use of corticosteroids and corticosteroid phobia in atopic dermatitis. Clinics in dermatology. 2003 May 1;21(3):193-200.
17. Staab D, Kaufmann R, Bräutigam M, Wahn U, CASM981CDE04‐Study Group. Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents’ quality of life: a multicenter, randomized trial. Pediatric allergy and immunology. 2005 Sep;16(6):527-33.
18. Naylor M, Elmets C, Jaracz E, Rico JM. Non‐melanoma skin cancer in patients with atopic dermatitis treated with topical tacrolimus. Journal of dermatological treatment. 2005 Jan 1;16(3):149-53.
19. Spergel JM, Leung DY. Safety of topical calcineurin inhibitors in atopic dermatitis: evaluation of the evidence. Current Allergy and Asthma Reports. 2006 Jul;6(4):270-4.
20. Thaci D, Reitamo S, Gonzalez Ensenat MA, Moss C, Boccaletti V, Cainelli T, Van Der Valk P, Buckova H, Sebastian M, Schuttelaar ML, Ruzicka T. Proactive disease management with 0· 03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. British journal of dermatology. 2008 Dec 1;159(6):1348-56.
21. Bieber T, Vick K, Fölster‐Holst R, Belloni‐Fortina A, Städtler G, Worm M, Arcangeli F. Efficacy and safety of methylprednisolone aceponate ointment 0.1% compared to tacrolimus 0.03% in children and adolescents with an acute flare of severe atopic dermatitis. Allergy. 2007 Feb;62(2):184-9.