Successful Treatment of Confluent and Reticulated Papillomatosis With Calcipotriene and Tretinoin: A Novel Topical Regimen

J Clin Aesthet Dermatol. 2025;18(9):55–57.

by Rajiv Nathoo, MD, and Fahad Siddiqui, DO

Dr. Nathoo is with Sun State Dermatology in Maitland, Florida. Dr. Siddiqui is with the Kansas City University GME Consortium/Advanced Dermatology and Cosmetic Surgery in Maitland, Florida.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors declare no conflicts of interest relevant to the content of this article.

Abstract: Confluent and reticulated papillomatosis (CARP) is a rare dermatosis of uncertain etiology characterized by scaly, hyperpigmented papules that coalesce into reticulated plaques, typically affecting the upper trunk of adolescents and young adults. While oral minocycline remains the most established treatment, relapse and adverse effects often are limiting factors. We present the case of a 25-year-old male patient with an 18-month history of CARP who experienced initial improvement with oral antibiotics but discontinued systemic therapy due to side effects. The patient was successfully treated with a novel topical regimen of calcipotriene 0.005% cream daily and tretinoin 0.05% cream nightly, achieving complete clearance after 3 months of consistent use without adverse effects. This case supports the role of disordered keratinization in CARP and demonstrates that topical calcipotriene and tretinoin may offer a safe and effective treatment alternative for patients who cannot tolerate or prefer to avoid systemic antibiotics. Keywords: Calcipotriene, confluent and reticulated papillomatosis, keratinization, topical therapy, tretinoin

Introduction

Confluent and reticulated papillomatosis (CARP) is a rare dermatosis that typically affects adolescents and young adults. It is characterized by asymptomatic, scaly, hyperpigmented papules that coalesce centrally and form a reticulated pattern at the periphery, most commonly on the trunk, neck, and upper chest.^1,2 While its etiology remains unclear, the most widely supported theories include disordered keratinization, colonization by Dietzia papillomatosis, and associations with endocrine or metabolic abnormalities such as insulin resistance and obesity.^1-3

CARP has often been misdiagnosed as tinea versicolor, due to similar morphology. However, poor response to antifungal therapy and absence of fungal organisms on microscopy or biopsy typically prompt reconsideration of the diagnosis.^2,4 The most established treatment has been oral minocycline, which demonstrates both antimicrobial and anti-inflammatory properties. Nonetheless, adverse effects and relapse after discontinuation are common.^5,6 Recent literature has highlighted the successful use of topical therapies such as tretinoin and calcipotriene used independently, which may provide effective alternatives for patients unable to tolerate systemic agents.^2,4,7-9 We present a case of CARP successfully treated with a novel topical combination of both calcipotriene and tretinoin.

Case Report

A 25-year-old male patient with no significant past medical history presented with an 18-month history of an asymptomatic rash that had been gradually spreading. He denied itching, pain, or tenderness. The patient had no known allergies, was not taking any medications, and had no history of prior dermatologic conditions. The patient provided informed consent and photoconsent.

On physical examination, grayish blue-brown, scaly macules were observed on the upper and mid-chest. Many of these macules coalesced into reticulated patches, forming a net-like pattern (Figure 1A). Based on the clinical presentation, a diagnosis of CARP was made.

The patient was initially started on oral minocycline 100mg twice daily for six weeks. At a four-week follow-up visit, he reported moderate clinical improvement and noted that the rash began to fade shortly after initiating treatment (Figure 1B). However, he also developed new symptoms of pruritus and Type III minocycline hyperpigmentation. Due to these adverse effects, minocycline was discontinued and substituted with doxycycline 100mg twice daily for two weeks.

The patient experienced severe gastrointestinal discomfort with doxycycline without significant clearance of the rash. Approximately one month after finishing the course of doxycycline, he presented with a recurrence of CARP (Figure 1C) and expressed a preference for topical therapy. He was started on a topical regimen of tretinoin 0.05% cream applied nightly (QHS) and calcipotriene 0.005% cream applied each morning (QAM). At a follow-up visit three months later, the patient reported consistent use of both topical agents and demonstrated clearance of lesions with no adverse effects (Figure 1D).

Discussion

The pathogenesis of CARP remains incompletely understood, but two leading theories predominate: infection with Dietzia papillomatosis, a gram-positive actinomycete, and intrinsic disorders of keratinization.^1,3 While earlier hypotheses implicated Malassezia furfur, subsequent studies found inconsistent fungal isolation from lesions, shifting attention toward bacterial and keratinization-related causes. Histopathologically, CARP lesions typically exhibit hyperkeratosis, papillomatosis, and basal hyperpigmentation, features characteristic of epidermal maturation abnormalities.^1,3,8

Oral minocycline is considered first-line therapy for CARP, with complete or partial resolution achieved in approximately 82 percent of cases, usually within 6 to 8 weeks.⁵ The presumed efficacy of minocycline derives from both its antimicrobial and intrinsic anti-inflammatory properties (Table 1).¹⁰ However, its use is limited by potential adverse effects, including drug-induced lupus, vestibular disturbances, and pigmentary changes.⁶ Doxycycline is an alternative with a safer side effect profile and demonstrated success in individual cases, although it is still considered second-line in most treatment algorithms.⁶ Other therapies, such as antifungals and keratolytics, have produced inconsistent results, likely reflecting misdiagnosis or suboptimal targeting of the underlying disease mechanism.⁵

Topical therapies that modulate keratinocyte proliferation and differentiation are alternative therapies targeting the proposed pathophysiology of CARP. Calcipotriene, a synthetic vitamin D3 analog, binds to the vitamin D receptor in keratinocytes, regulating gene transcription to normalize differentiation, suppressing aberrant keratin 16 expression, and reducing epidermal hyperplasia.^4,8 These effects counteract the epidermal dysregulation seen in CARP, offering a rational, mechanism-based approach to therapy. Successful use of calcipotriene for CARP has been reported in isolated cases, with minimal side effects.^4,8

Tretinoin, a topical retinoid, complements this approach by binding to nuclear retinoic  acid receptors and promoting keratinocyte turnover. It facilitates orderly desquamation, reduces intercellular cohesion within the stratum corneum, and improves abnormal epidermal maturation.^2,9,11 Additionally, tretinoin may downregulate proinflammatory cytokine expression, potentially addressing any secondary inflammatory components of CARP.¹¹

In our patient, the combination of calcipotriene applied in the morning and tretinoin applied nightly led to rapid and sustained clearance after oral antibiotics were trialed. The tetracycline class of antibiotics led to intolerable side effects and did not provide as robust a response compared with the topical regimen. The complementary mechanisms of these two agents—calcipotriene normalizing keratinocyte differentiation and tretinoin accelerating epidermal turnover—likely acted synergistically to restore epidermal homeostasis.

Our case adds to the growing body of evidence that CARP, at least in a subset of patients, can be effectively managed with topical therapies targeting keratinization. Given the chronic nature of CARP, the potential adverse effects of long-term systemic antibiotic use, and the generally benign clinical course of the disease, topical regimens such as calcipotriene and tretinoin may represent a safer and highly effective alternative.

Conclusion

This case highlights the successful use of topical calcipotriene and tretinoin in the management of CARP. In patients who cannot tolerate systemic antibiotics or prefer topical options, this dual-agent regimen offers an effective, well-tolerated alternative. The therapeutic response observed in our case adds to the growing body of evidence that supports the role of disordered keratinization in CARP and the value of targeted topical therapy. Further studies are warranted to assess long-term outcomes, optimal duration of treatment, and recurrence rates associated with this approach.

References

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