Beyond the Herald Patch: Exploring the Complex Landscape of Pityriasis Rosea

Abstract

Pityriasis rosea (PR) is a prevalent dermatological condition characterized by a distinctive herald patch, followed by secondary eruptions, often forming a “Christmas tree” pattern on the trunk. Despite its recognizable clinical presentation, the etiology of PR remains uncertain, with hypotheses pointing to both infectious and noninfectious origins. Human herpesviruses (HHV) 6 and 7 have been implicated, with evidence suggesting viral reactivation as a potential trigger. Epidemiologically, PR affects children, adolescents, and young adults, with a higher incidence in females. The condition is observed globally, with varying incidence rates and seasonal variations, suggesting an infectious component. While PR is generally benign and self-limiting, it can cause significant discomfort owing to pruritus, and atypical presentations and recurrences complicate diagnosis and management. This review evaluates the current understanding of PR’s pathogenesis, highlighting both infectious and noninfectious hypotheses, including viral reactivation and immune response mechanisms. It also examines treatment options, such as antivirals and phototherapy, which have shown varying degrees of effectiveness. Further research is needed to clarify etiological factors and to explore the efficacy and safety of various treatment modalities. Understanding these aspects is crucial for improving patient outcomes and developing targeted therapies, especially for atypical or recurrent cases.

Key Points

This review investigates the potential infectious and noninfectious causes of pityriasis rosea (PR), emphasizing the possible role of human herpesviruses 6 and 7, viral reactivation, and immune response mechanisms in its pathogenesis.

We provide a comprehensive overview of PR’s prevalence, highlighting its higher incidence in females and younger populations, as well as seasonal variations that suggest an infectious component.

Limitations of current treatment options, including steroids, macrolides, antivirals, and phototherapy, underscore the need for further research to assess their efficacy and safety, particularly for atypical or recurrent PR cases.

Introduction

Pityriasis rosea (PR) is a common, self-limiting dermatological condition characterized by distinctive skin lesions, including a herald patch, followed by secondary eruptions that often form a “Christmas tree” pattern on the trunk [1, 2]. Despite its recognizable clinical presentation, the etiology of PR remains largely uncertain, with hypotheses suggesting both infectious and noninfectious origins. Notably, human herpesviruses (HHV) 6 and 7 have been implicated in its pathogenesis, with evidence pointing to viral reactivation as a potential trigger for the condition [3, 4].

Epidemiologically, PR predominantly affects children, adolescents, and young adults, with a higher incidence reported in females compared with males [5–8]. The condition is observed worldwide, with varying incidence rates of around 0.5–2% or greater [1, 5, 6, 9]. In the USA, a study utilizing the All of Us database found that PR affects approximately 0.13% of the population, with a higher prevalence in females and individuals aged 10–29 years [10]. This aligns with global patterns, where PR is more common in younger populations. Seasonal variations have also been noted, with some studies suggesting a higher incidence during the fall and winter months [8, 11, 12]. In Eastern Anatolia, Turkey, a study analyzing 391 patients with PR from 1992 to 1995 reported an average annual incidence of 0.75 per 100 dermatologic patients, with a slightly higher prevalence in females and a peak incidence in the 20–29 year age group [6]. The incidence was notably higher during the rainy and snowy months [6]. In Kaduna, Nigeria, PR was found in approximately 2.4% of dermatology clinic attendees, with a significant number of cases occurring during the rainy season [13].

While PR is generally considered benign and self-limiting, it can cause significant discomfort owing to pruritus, which affects the majority of patients. The condition typically resolves spontaneously within 6–8 weeks, though atypical presentations and recurrences can occur, complicating diagnosis and management [4]. Understanding the epidemiological patterns and clinical manifestations of PR is crucial for effective diagnosis and patient reassurance, as well as for guiding future research on its underlying causes and potential treatments.

Etiology and Pathophysiology

Despite its common incidence and distinct clinical presentations, the exact cause of PR remains unknown owing to conflicting evidence. However, there are numerous hypotheses implicating both infectious and noninfectious factors.

Infectious Hypotheses

A large body of literature points to the possibility of an infectious origin of PR, due to its seasonal variations, familial clustering, and prodromal presentations [1, 14]. PR occurs more commonly during the winter, outbreaks happen in clusters, and patients often report upper respiratory infection-like symptoms preceding PR lesions [15, 16]. In addition, only 1–3% of patients experience second episodes, and even fewer report more than two recurrences, often with smaller and fewer lesions [4, 17]. Although there is no consistent pattern regarding morphology, age, or sex affected, a few studies note the association between recurrences and episodes of stress, suggesting the role of viral reactivation in PR recurrence [17, 18].

Studies have reported different viruses, bacteria, and spirochetes as causative pathogens of PR, such as cytomegalovirus (CMV), Epstein–Barr virus, parvovirus B19, picornavirus, influenza and parainfluenza viruses, Legionella spp., Mycoplasma spp., and Chlamydia spp. but failed to identify a single infectious agent [11, 14]. There has also been a growing discussion of human herpesviruses (HHV) 6 and 7 in the etiology of PR. HHV-7 DNA is frequently detected in blood and saliva of patients with PR [17, 19, 20]. Studies suggest a link between primary infection of HHV-6 or HHV-7 in early childhood and its manifesting as PR in future systemic reactivation [21]. A few studies explored the role of Streptococcus in causing PR as patients had preceding upper respiratory infections and increased antistreptolysin O (ASLO) titers [22], although this was not supported in future studies [23].

Despite limited understanding of the mechanisms and cytokine profiles involved in PR, significant immunological research over the past four decades has aimed to identify inflammatory mediators and triggers. Research suggests that cell-mediated immunity plays a role in PR’s development [24]. Aiba and Tagami discovered immunohistological evidence of cellular immune responses in affected skin, noting an increase in mononuclear cells, active CD4+ T-helper cells, and Langerhans cells [25]. Sugiura et al. then demonstrated that the rise in Langerhans cells and the T-helper to T-suppressor/cytotoxic ratio correlated with the disease’s stage and severity [26]. Further studies by Neoh et al. [27] and Baker et al. [28] confirmed these findings, showing increased markers for T cells and Langerhans cells, but not for B cells or natural killer (NK) cells. Bos et al. [29–31] also examined immune cell distribution and types in PR, reinforcing the involvement of cell-mediated immunity. Additionally, studies analyzing PR patients’ sera support these findings. Drago et al. identified elevated levels of interferon alpha, interleukin 17, and vascular endothelial growth factor [32], while Gangemi et al. reported higher levels of fractalkine [33] and interleukin 22 [34] in two different papers. These studies highlight immune responses typical of viral infections, providing indirect evidence for PR’s proposed viral origin.

Noninfectious Hypotheses

Pityriasis Rosea-Like Eruptions Post-vaccination

PR-like eruptions have been reported following various vaccinations, including Bacillus Calmette-Guérin (BCG), influenza, polio, H1N1, diphtheria-pertussis-tetanus, smallpox, papillomavirus, Hepatitis B, pneumococcus, and COVID-19 [35–38]. Papakostas et al. proposed that vaccines may trigger a T-cell mediated response and that the activated immune system thus reactivates the pathogen [39, 40]. In fact, it has been suggested that the pathophysiology of PR is predominantly T-cell mediated, supported by the proliferation of T-cells and the lack of natural killer (NK) cells and B-cells found in PR lesions [35, 41]. The presence of anti-immunoglobulin M (IgM) keratinocytes in PR patients also suggests that this immune response is responsible for the clinical signs of PR [1, 40].

Drug-Induced Pityriasis Rosea-Like Eruptions

There have also been reports of patients developing lesions resembling PR following new administration of medications (Table 1). Drug-induced PR-like eruptions usually occur without a herald patch or typical collarette scaling and may require lower dosage or discontinuation of the drug to resolve [35, 42]. Table 1 displays many of the drugs or associated drug classes that have been reported to cause PR.

Table 1.

Drug-induced pityriasis rosea rash features and supporting studies

Drug or drug class name	Rash features	Studies documenting the reaction
ACE inhibitors	Erythematous, generalized, maculopapular eruptions over the trunk, abdomen, and proximal aspects of the limbs within 2 weeks, resolved a week after lowering dose or discontinuation	Atzori et al. [43] Wilkin et al. [44] Wilkin et al. [45] Ghersetich et al. [46] Reinhardt et al. [47]
Beta blockers	Diffuse, bright red to violet color, pruritic scaly patches on trunk and extremities after 3 weeks, resolved after lowering dose or discontinuation	Güleç et al. [48] Wilkin et al. [45]
Bismuth	Multiple oval patches, papules, and plaques primarily on the abdomen, chest, back, and buttock, with some involvement of the bilateral upper extremities within 24 hours	Hanjani et el. [49] Dobes et al. [50]
Domperidone	Scattered erythematous and squamous lesions on the arms, chest, and abdomen, confluently scaly plaques of the lower back 5 days post drug. Resolved 2 weeks after discontinuation	Saad et al. [51]
Gold salts	Scaling, raised, erythematous plaques over the trunk and face after 6 months, cleared in 5 months without discontinuation	Corke et al. [52] Bonnetblanc [53] Wilkinson et al. [54]
Imatinib	Mildly erythematous, oval-to-round papules with or without a herald patch, thin plaques with a fine collarette of scale distributed over the trunk and proximal extremities, resolved with topical steroid or discontinuation	Konstantopoulos et al. [55] Durgin et al. [56] Işık et al. [57] Cho et al. [58] Valenzuela-Ubiña et al. [59] Verma et al. [60] Brazzelli et al. [61]
Interferon	Erythematous lesions, oval-shaped and salmon pink in color, over trunk and upper extremities with peripheral scales, circular lesions with central clearing on chest and upper abdomen, spontaneous recovery or with topical treatment	Güner et al. [62] Drago et al. [63] Durusoy et al. [64]
Isotretinoin	Lesions with psoriasiform hyperplasia, resolved with lower dose	Gürel et al. [65] Heffman et al. [66]
Levamisole	Round, scaled, erythematous plaques over the trunk after 6 months and cleared with temporary pause of the drug	Corke et al. [52]
Metronidazole	Widespread mildly pruritic rash involving mainly the trunk and proximal upper limbs. The eruption was characterized by numerous erythematous plaques measuring 1–3 cm in diameter, many of which had peripheral scale, resolved after discontinuation	Buckley [67] Maize et al. [68]
NSAIDs	Multiple erythematous papules and plaques with collarette scaling present all over the body with violaceous pigmentation on lips, resolved after treatment including oral steroids, antihistamines, and emollient	Yosipovitch et al. [69] Behera et al. [70]
Omeprazole	Truncal lesions resolved after discontinuation	Buckley [67]
Ondansetron	Erythematous papulosquamous lesions characterized by annular scaly margins and a dusky center over the arms, chest, abdomen, lower back and legs 2 days post drug. Resolved 4 weeks after discontinuation	Alame et al. [71]
D-Penicillamine	Annular macules with central areas of scaling over the trunk and proximal limbs after 2 months, cleared in 2 months without discontinuation	Corke et al. [52]
Terbinafine	Pruritic erythematous scaly eruption on the trunk and upper and lower extremities, many with a collarette of scale, cleared after discontinuation with supportive therapy	Gutpa et al. [72] Nenoff et al. [73] George et al. [74]
Tricyclic antidepressants	Erythematous, well-defined, oval papules and patches, with fine collarettes of scale on the dorsal hands, upper arms, and trunk, cleared with discontinuation	Bangash et al. [75]
TNF-alpha Inhibitors	Multiple erythematous patches and plaques of varying sizes and shapes on the trunk and proximal limbs, with a “Christmas tree” pattern on the back. Most lesions with a collarette of scales and central clearing	Rajpara et al. [76] Miyoshi et al. [77] Guarneri et al. [78]

ACE angiotensin-converting enzyme; TNF tumor necrosis factor

Clinical Characteristics/Features

Pityriasis rosea (PR) is often clinically identified by the presence of a “herald patch,” which is typically a single, large, slightly raised, oval or round erythematous scaly patch that appears on the trunk or neck. This patch is usually pink or salmon-colored and ranges from 2 to 10 centimeters in diameter [79] and is observed in 50–90% of patients [1]. Within a few days to 2 weeks after the herald patch appears, multiple smaller scaly, oval, pink, or salmon-colored plaques with fine scaling edges develop [1]. These secondary lesions often align along the cleavage lines of the trunk and limbs, creating a characteristic "Christmas tree" pattern [80]. While the rash primarily affects the trunk and limbs, it can also appear on the neck, arms, and legs, though it rarely involves the face, palms, or soles [1]. These lesions present as elliptical or oval macules and papules, exhibiting fine scaling and a central wrinkling that resembles cigarette paper [81]. A distinctive feature of PR is the collarette scale appearance, where the scale is attached at the periphery but lifted near the center [81]. The distribution of lesions is generally bilateral and diffuse, with the long axis parallel to the skin tension lines [81].

Moreover, oropharyngeal lesions can occur in up to 28% of patients with pityriasis rosea (PR) [82]. These lesions are painless and are typically associated with the exanthem of PR. The most frequently observed patterns include petechial and macular and papular lesions. While petechial enanthema has been predominantly associated with persistent PR and pediatric PR, macular and papular lesions are seen across various forms of the disease, including relapsing PR and classic PR [82]. Thus, it is important to examine the oropharyngeal mucosa in patients with PR, as the presence of these lesions can help distinguish PR from other mucosal diseases and may indicate a more atypical course of the disease (e.g., persistent or relapsing forms).

Some patients may experience mild prodromal symptoms before the appearance of the herald patch, including a sore throat, gastrointestinal disturbances, fever, and arthralgia [14]. Although the rash may be asymptomatic, some individuals may experience mild to moderate itching, which can worsen with heat or sweating [14]. Severe itching occurs in about 25% of cases [1]. Occasionally, patients may also experience gastrointestinal symptoms, joint pain, or slight enlargement of lymph nodes [14]. The rash of pityriasis rosea typically resolves within 6 to 8 weeks in more than 80% of patients, though it may persist longer in some cases [1]. It usually resolves spontaneously without leaving scars, and the herald patch may last longer than the secondary lesions [1]. Figure 1 shows the classic presentation of pityriasis rosea on the chest, with oval erythematous patches distributed along skin tension lines in a ‘Christmas tree’ pattern.

Fig. 1.

Classic pityriasis rosea on the chest and neck, with oval macules and patches arranged along skin tension lines in a “Christmas tree” pattern

Atypical Variants of PR

Atypical variants of pityriasis rosea account for approximately 20% of all cases [42].These variants can differ significantly from the classical presentation—owing to morphology, size, distribution, course, or symptoms—making diagnosis more challenging [14]. Current research suggests that children are more predisposed to atypical variants of PR in comparison with adults, with atopy playing a possible role [14].

Atypical pityriasis rosea (PR) can present in diverse forms, deviating from the classic herald patch followed by smaller lesions [42]. It may include vesicular, purpuric, urticarial, or papulovesicular lesions and, rarely, erythema multiforme-like or targetoid lesions [42]. The size of these lesions varies, with some significantly smaller or larger than the typical 2–10 cm diameter [42]. Unlike the usual “Christmas tree” pattern, atypical lesions may appear in unusual locations such as the face, palms, soles, or mucous membranes, which are generally spared in classic cases [14]. The rash duration can also differ, sometimes lasting longer than the typical 6–8 weeks or resolving more quickly [14]. While classic PR is often asymptomatic or mildly itchy, atypical forms may present with more severe symptoms, including significant pruritus, especially upon contact with sweat, leading to excoriations, pain, or systemic symptoms like fever and malaise [42].

A variety of atypical morphologies have been described in the literature. Vesicular PR is characterized by a generalized eruption of small vesicles, 2–6 mm in size, or vesicles arranged in a rosette pattern [83]. This variant, often seen in children, can affect the head, palms, and soles and may be intensely pruritic [83]. Purpuric or hemorrhagic PR present as macular purpura on the skin or oral mucosa, while urticarial PR features lesions similar to urticarial wheals, accompanied by intense itching [84, 85]. Generalized papular PR, although rare, is more frequently observed in young children, pregnant women, and Afro-Caribbeans [86]. It presents with multiple small papules (1–2 mm) alongside classic patches and plaques [86].

Lichenoid PR, occasionally observed in atypical cases, is often drug-induced, associated with medications such as gold compounds, captopril, barbiturates, D-penicillamine, and clonidine [87]. Erythema multiforme-like PR includes targetoid lesions with classic PR rash; histopathological examination may show satellite cell necrosis, a feature specific to erythema multiforme [87]. Follicular PR involves follicular secondary lesions, either grouped or isolated, with differential diagnoses including follicular lichen planus, keratosis pilaris, and atopic dermatitis with a follicular component [88]. Giant PR, a rare variant named after Darier, consists of unusually large plaques ranging from 5 to 7 cm, sometimes reaching the size of the patient’s palm [14]. PR can also present as exfoliative dermatitis, characterized by widespread scaling and erythema [14].

An atypical herald patch may be absent in up to 20% of cases or may appear at unusual sites such as the face, scalp, or genitalia [14]. Inverse PR primarily affects acral and flexural areas, including the axilla, groin, and face [89]. Acral PR features lesions on the palms and soles, necessitating differentiation from conditions like erythema multiforme, syphilis, necrolytic acral erythema, and drug eruptions [90, 91]. Unilateral PR is an extremely rare form in which lesions appear only on one side of the body, observed in both children and adults [92, 93]. Blaschkoid PR follows the lines of Blaschko, which are thought to trace the path of embryonic ectodermal cell migration running along but not crossing the anterior truncal midline [94]. Limb-girdle PR, also known as PR of Vidal, is confined to the shoulders or pelvic girdle, typically affecting the axilla and groins with larger, more annular lesions [14]. Mucosal involvement in PR occurs in about 16% of patients, affecting the oral mucosa with punctate, erosive, bullous, or hemorrhagic lesions, often without symptoms [14]. Localized PR presents with eruptions confined to a specific area of the body [95, 96].

In individuals with darker skin tones, PR may present differently, more frequently involving the face and manifesting with papular lesions [97]. Additionally, oral ulcers have been reported to occur more often in skin of color patients [3]. These cases tend to be more pruritic, and post-inflammatory hyperpigmentation is a common outcome [97].

Despite these variations, typical clinical features, such as a preceding prodrome, a primary lesion followed by secondary lesions, and coexistent classical lesions, are still beneficial in diagnosing most PR cases [14]. Figure 2 shows atypical lesions of pityriasis rosea on the hand, an uncommon site for this condition as the rash typically spares the distal extremities.

Fig. 2.

Atypical pityriasis rosea lesions on the hand, presenting as round, erythematous plaques with peripheral scaling

Recurrent Pityriasis Rosea

Although PR is a common disorder among children and young adults, recurrent PR is rare, found in only 1–3% of known cases [98]. Multiple recurrences (three or more episodes) are extremely uncommon, and only a few patients have been identified [98].

Several factors are thought to trigger recurrent PR, including viral reactivation, drug-induced episodes, and immune system alterations. Reactivation of human herpesvirus 6 (HHV-6) and HHV-7, which are also linked to the initial PR episode, has been identified as a possible cause of recurrence [12]. These viruses may remain dormant and be reactivated by stress or immunosuppression [12]. Certain medications, such as ACE inhibitors, NSAIDs, and some antibiotics, have also been implicated [14]. These drug-induced cases often mimic idiopathic PR, complicating diagnosis [14]. Additionally, immune system dysfunction, either due to underlying health conditions or external factors such as infections, might contribute to PR recurrence, though this area requires further study [14].

Recurrent PR episodes often resemble the initial rash in appearance and distribution [99]. However, they can differ in duration, severity, and pattern of distribution to be more localized or involve different anatomic areas [98, 99]. For some patients, recurrent episodes are shorter, while others may experience longer durations compared with the initial episode [99]. The interval between episodes can vary significantly, ranging from a few months to several years. Some studies suggest that recurrent episodes tend to be milder, with less body surface involvement and fewer systemic symptoms [99]. However, this is not always the case, as some patients report equally or even more severe symptoms during recurrences [98].

Before diagnosing recurrent PR, it is crucial to rule out other conditions that may mimic the rash, particularly if the presentation differs from the typical PR pattern. Conditions such as tinea corporis, secondary syphilis, and drug-induced rashes should be initially excluded [3]. A thorough history, including details about recent drug use, sexual history, and infections, is essential in the diagnostic workup [3]. Serological testing for syphilis and other infections should be performed, especially if the patient is at high risk or the rash appears atypical [3]. If the diagnosis remains uncertain, a skin biopsy may be useful [14]. However, because PR is rarely biopsied, many cases labeled as recurrences may not be true PR recurrences. This diagnostic uncertainty is further complicated by the self-limiting nature of PR, which often resolves without intervention, making it less likely for clinicians to pursue biopsy in recurrent or atypical cases. Thus, caution should be exercised when diagnosing recurrences without biopsy confirmation. Histopathological examination can help distinguish PR from other mimicking conditions [14]. If a drug-induced cause is suspected, discontinuing the offending medication and considering alternative treatments is recommended [14].

Pityriasis Rosea in Pregnancy

Pityriasis rosea during pregnancy, although rare, has been associated with an increased risk of adverse pregnancy outcomes, particularly when it occurs in the first trimester. Earlier studies, such as those by Drago et al. [100], reported a higher risk of miscarriage (up to 57–62%) in women who developed PR before the 15th week of gestation, particularly when the rash was extensive or accompanied by systemic symptoms like fever and malaise. However, recent findings offer a more nuanced perspective. Wenger-Oehn et al. [101] conducted a case series involving 46 pregnant women with PR and found a significantly lower rate of unfavorable outcomes (10.9%) compared with a pooled cohort of previous reports (39.6%). Their study highlighted that the timing of PR onset, rash distribution, and the presence of extracutaneous symptoms were key factors influencing pregnancy outcomes, with earlier onset and widespread rash being associated with higher risks [101].

Despite these concerns, the majority of pregnancies affected by PR result in healthy deliveries. Chuh et al. [102] and other studies have also noted that PR occurring later in pregnancy is typically associated with more favorable outcomes [100, 103]. Given the variability in outcomes, pregnant women with PR, especially those in the early stages of gestation or presenting with widespread rashes or systemic symptoms, should be closely monitored by their healthcare providers.

Clinical, Histologic, and Molecular Features of the Herald Patch

The herald patch, a hallmark of classic pityriasis rosea (PR), is typically the first lesion to appear and is often larger and more well-defined than the subsequent smaller lesions. Clinically, it presents as a solitary, oval or round, erythematous plaque with a fine, trailing edge of scale, often referred to as a “collarette.” This lesion is commonly found on the trunk or proximal limbs and precedes the generalized eruption by several days to 2 weeks [4, 5].

Histologically, the herald patch can exhibit features similar to other inflammatory dermatoses, with a superficial perivascular lymphohistiocytic infiltrate and mild spongiosis [35, 104]. However, some studies suggest that the herald patch may show more prominent epidermal changes compared with the secondary lesions, such as parakeratosis and focal necrosis of keratinocytes [35, 105]. Molecular differences between the herald patch and subsequent lesions have not been extensively characterized, though studies imply that viral reactivation, particularly of human herpesvirus 6 (HHV-6) and HHV-7, may play a role in initiating the herald patch [106–108].

Presence of the Herald Patch in PR Variants

The presence of a herald patch is a key feature of classic PR, but it may be absent in atypical variants of the condition. In inverted PR, where the lesions predominantly involve the flexural areas, a herald patch may be less easily identified or entirely absent [41]. Similarly, in localized PR, the exanthem may be confined to one area, and a distinguishable herald patch may not be present [4, 109, 110]. Persistent PR and relapsing PR also tend to have more varied presentations, with a herald patch being less commonly reported [4, 111, 112].

In pediatric PR and PR associated with COVID-19, the presence of a herald patch is variable [113, 114]. Studies have suggested that in COVID-19-related PR-like eruptions, the exanthem may present without a classic herald patch, mimicking the morphology of viral exanthems [113, 115]. Identifying the herald patch can be crucial for diagnosis, but its absence should not rule out PR, particularly in atypical or variant forms, where the clinical course and morphology of lesions may differ.

Evaluation, Diagnosis, and Differential Diagnosis

Diagnostic Criteria

Owing to the absence of standardized diagnostic guidelines and the frequent occurrence of atypical cases, Chuh et al. [80] proposed a set of diagnostic criteria for pityriasis rosea. These criteria are categorized into essential, optional, and exclusional clinical features to facilitate accurate diagnosis [80]. Table 2 summarizes these features.

Table 2.

Diagnostic criteria for pityriasis rosea [80]

Category	Criteria
Essential clinical features	1. Well-defined, round or oval skin lesions
	2. Presence of scaling on the majority of lesions
	3. At least two lesions show a distinctive ring of scaling around the edges (collarette scaling) with clearer centers
Optional clinical features	1. Lesions primarily located on the trunk and upper parts of the limbs, with fewer than 10% found beyond the mid-upper arm and mid-thigh
	2. Lesions tend to follow the rib lines
	3. An initial lesion (herald patch) appears at least two days before the rest of the rash, though it may not be the largest
Exclusional clinical features	1. Presence of small blisters in the center of two or more lesions
	2. Majority of lesions located on the palms or soles
	3. Evidence of secondary syphilis, such as generalized swollen lymph nodes or positive blood tests

Dermoscopy as an Aid in Diagnosis

Dermoscopy can be a useful tool in the evaluation of PR. The herald patch and the secondary lesions of PR typically show a characteristic peripheral whitish scaling (called a “collarette” sign) as well as dotted vessels, which, contrasting with psoriasis, are distributed in an irregular or focal pattern. Diffuse or localized yellowish-orange structureless areas may be visible as well [81]. The central area of the lesion may show less scaling and a more homogeneous appearance, and sometimes, dermoscopy also reveals a faint vascular network or linear vessels within the lesions [81]. These findings can help distinguish PR from other conditions and should be used in conjunction with clinical evaluation.

Histopathological Findings

Histopathology can also be used as a diagnostic tool to confirm the diagnosis of PR in atypical cases and help differentiate PR from other similar-looking conditions. Common epidermal changes include focal parakeratosis in mounds with exocytosis of lymphocytes, variable spongiosis, mild acanthosis, and a thinned granular layer [3]. In the dermis, extravasated red blood cells are found accompanied by a perivascular infiltrate of lymphocytes, eosinophils, and monocytes [3]. The herald path usually exhibits deep infiltrates and more acanthosis [3]. In atypical cases, dyskeratotic cells may also be present, and virus-like particles in various stages of morphogenesis have been found in patients with PR [3]. Additionally, the absences of acantholysis or significant dyskeratosis can be used to differentiate PR from conditions like pemphigus or Grover’s disease [3].

Differential Diagnosis

Several conditions may mimic PR and should be considered in the differential diagnosis. Below is a list of common differentials with brief descriptions of why they need to be ruled out:

• Secondary syphilis: Often presents with a generalized rash, including on palms and soles, which can resemble PR but usually lacks a herald patch and has a different distribution, and lymphadenopathy is almost always found in secondary syphilis but usually never in PR [3]. A rapid plasma reagin test is essential to rule out this condition.

• Tinea corporis: Fungal infections can present with annular, scaly lesions that may mimic PR [2]. A potassium hydroxide (KOH) preparation can confirm the diagnosis by revealing fungal elements.

• Erythema multiforme: This condition can present with targetoid lesions and mucosal involvement, which is not typical of PR [116]. A detailed history and clinical examination help distinguish between the two, as erythema multiforme is often related to herpes simplex infection.

• Guttate psoriasis: Characterized by small, rain-drop pattern, scaly papules, guttate psoriasis may resemble PR but often has a history of sore throat and psoriasis, scales are thicker and silvery-white, and it lacks the typical herald patch [117].

• Pityriasis lichenoides chronica: Chronic, scaly, red–brown papules that may resemble PR, but lesions persist longer, the herald patch is lacking, and papules are in different stages of evolution, one or more of them showing a darker center and have a more varied appearance [3]. Histopathology is often needed for differentiation [3].

• Pityriasis alba: Hypopigmented, scaly patches usually seen in children with a history of eczema [118]. The absence of a herald patch and the chronic nature of the condition help differentiate it from PR [118].

• Lichen planus: Pruritic, purple, polygonal papules often involving the wrists, lumbar spinal region, glans penis, and oral mucosa [2]. The chronicity and distribution help differentiate it from PR [2].

• Subacute cutaneous lupus erythematosus: Erythematous, annular, or polycyclic lesions that may mimic PR but often have photosensitivity and systemic symptoms, and histology shows epidermal atrophy and basal layer degeneration [117].

• Nummular eczema: Coin-shaped, scaly patches that may resemble PR. The chronic, relapsing nature, intense pruritus, and shin and dorsal hand localizations, rarely found in PR, are key differentiators [3].

• Cutaneous T-cell lymphoma: Early stages may resemble PR, as the initial patch does not respond to topical steroids mimicking PR [14]. However, cutaneous T-cell lymphoma typically has a chronic course and does not respond to standard PR treatments. Multiple serial biopsies are essential for diagnosis [14].

• Kaposi sarcoma: Can present with red, purple, or brown plaques and nodules. Unlike PR, Kaposi sarcoma is associated with immunosuppression and has a more progressive course [119].

Differential Diagnosis of Atypical Pityriasis Rosea

In cases of atypical PR, particularly when systemic symptoms are present or when the herald patch is absent and the exanthem is widespread, it is essential to consider other infectious exanthems in the differential diagnosis. Epstein–Barr virus (EBV) and Parvovirus B19 are two potential infectious agents that can present with exanthems similar to PR.

EBV, a herpesvirus, can cause a variety of dermatological manifestations, including morbilliform, papulovesicular, and petechial eruptions during systemic infection. In some cases, EBV can lead to a florid morbilliform eruption or other atypical exanthems, which may resemble PR [120, 121]. EBV-associated exanthems may also be accompanied by systemic symptoms such as fever, lymphadenopathy, pharyngitis, and fatigue, which can overlap with the prodromal symptoms of PR. A thorough clinical history, including serological testing for EBV (e.g., positive viral capsid antigen IgM in acute infection), can help differentiate EBV-related exanthems from PR in patients presenting with systemic signs [120, 121].

Similarly, Parvovirus B19 should be considered in patients with an atypical PR-like presentation and systemic involvement. Parvovirus B19 is known to cause erythema infectiosum, which can mimic PR with its characteristic facial rash (‘slapped cheek’ appearance) and systemic symptoms, such as fever and arthralgia. In some cases, Parvovirus B19 infection can present with a widespread, nonspecific exanthem that can be confused with PR [122].

Given the overlapping clinical features between PR and these viral exanthems, particularly in the setting of systemic symptoms, serological testing for EBV and Parvovirus B19 may be considered to exclude these infectious causes. This is particularly important in cases where the herald patch is absent or the rash is more generalized and atypical in distribution.

Treatments

PR is a self-limiting disease with a low risk of transmission and typically resolves on its own within weeks to a few months; for most patients, monitored waiting and symptomatic treatment are sufficient [1]. General measures such as moisturizing, using emollients, and applying topical steroids can help alleviate itching or discomfort, while oral antihistamines may also provide relief [35]. However, using stronger therapies is generally discouraged due to the unclear underlying etiopathology and the challenges in evaluating the specific effects of these treatments [15]. Given that the disease usually resolves spontaneously, clinicians should carefully compare the benefits of potentially faster resolution with the risk of side effects or drug resistance if considering more potent therapeutics.

Steroids

Both topical and systemic steroids are occasionally used to treat PR, but evidence for their effectiveness is limited. A randomized placebo-controlled double-blind study found that tapering daily low-dose of prednisolone 20 mg to 10 mg for 15 days helped with rash clearance at 2 weeks but showed a higher relapse rate at 12 weeks, indicating a potential viral reactivation after initial suppression [123]. A study by Leonforte found that corticosteroid treatment worsened PR symptoms, including itching, irritation, and new lesion formation, especially when started in the early stages [124]. Given PR’s viral nature, oral steroids may not be ideal, and topical steroids should be limited to severely pruritic cases to prevent skin atrophy associated with prolonged use [35].

Antihistamines

Antihistamines are also often administered topically and orally to patients to mitigate irritation and trouble sleeping [35]. A recent report suggests that systemic antihistamines, combined with a moisturizing cream, accelerated the healing of lesions in COVID-19-related PR, indicating their potential role in reducing SARS-CoV-2-induced inflammation [125]. There has also been some evidence of the oral antihistamine dexchlorpheniramine in improving PR rash clearance [15].

Macrolides

In a nonrandomized, placebo-controlled study, Sharma et al. found that 73% of patients on a 2-week oral erythromycin regimen achieved complete clearance of PR by week 6 [22]. Subsequent randomized controlled studies yielded conflicting results [126–128]. A Cochrane systematic review by Conteras-Ruiz et al. reported at least fair-quality evidence from 14 studies with 761 participants [129], indicating: no evidence for oral clarithromycin or azithromycin (RR 0.84, 95% CI 0.47–1.52; RR 0.83, 95% CI 0.28–2.48), weak evidence for erythromycin in rash and itch improvement (RR 4.02, 95% CI 0.28–56.61; MD 3.95, 95% CI 3.37–4.53), and moderate evidence for acyclovir in itch reduction (RR 0.34, 95% CI 0.12–0.94). The potential therapeutic effects of macrolides on PR are thought to arise from their anti-inflammatory and immunomodulatory properties rather than antibiotic action, but antibiotic resistance poses a significant risk [14].

Antivirals

Evidence supports the effectiveness of antivirals, particularly acyclovir, in treating PR, likely due to the involvement of HHV-7 and HHV-6 [14]. A systematic review of three randomized controlled trials found acyclovir significantly improved rash outcomes (RR 2.45, 95% CI 1.33–4.53) [129], and a meta-analysis of seven studies showed it effectively cleared lesions by week 1 (RR 5.72, CI 2.36–13.88) [130]. Acyclovir improved rash and pruritus in both high (800 mg daily) and low (400 mg daily) doses [131]. Its therapeutic effect is limited to HHV-6, as HHV-7 lacks the thymidine kinase gene that acyclovir targets, while other antivirals like cidofovir and foscarnet have more severe side effects and have not been studied in PR [2, 14].

Some studies have demonstrated that high-dose acyclovir (800 mg five times daily for 7 days) is effective for the resolution of PR lesions, particularly when administered early, with notable reductions in erythema and pruritus [130, 132]. However, other randomized clinical trials have reported no significant difference between acyclovir and placebo in the duration of disease resolution, suggesting that acyclovir may not be universally effective [133]. A meta-analysis by Chang et al. supported the efficacy of acyclovir in reducing erythema and lesion formation but highlighted that its benefits are primarily seen in high-dose regimens during the early course of PR [134]. Therefore, while acyclovir may be beneficial in certain cases, it is not recommended for all patients and should be considered primarily for those with severe pruritus, extensive rash, or early disease onset. For most patients with mild to moderate PR, supportive care with topical corticosteroids and oral antihistamines remains the preferred approach.

Phototherapy

Several studies have investigated narrowband UV-B and phototherapy for severe PR, finding that patients generally experienced less severe and pruritic lesions [135, 136], though one study noted improvement only in itch severity [137]. Only one report indicated that phototherapy worsened PR symptoms [138]. Low-dose ultraviolet (UV)-A1 radiation has shown promising results in improving itch and rash clearance [139]. Overall, the immunomodulatory and anti-inflammatory effects of phototherapy have been shown to improve PR rash and itch [136, 139], but further research is needed to find optimal dosing and wavelength regimens. Table 3 summarizes the main PR treatments.

Table 3.

Summary of pityriasis rosea treatments, dosages, and evidence levels

	Treatment	Common dosages	Duration of therapy	Level of evidencea
Topical	Emollients [15]	Varies	PRN	Level III
	Antihistamine creams [15]	Varies	PRN	Level III
	Corticosteroids [15]	Varies	Up to 3 weeks	Level III
Systematic	Antihistamines (dexchlorpheniramine) [15]	4 mg 2 times daily	2 weeks	Level III
	Corticosteroids (betamethasone) [140]	500 mcg 2 times daily	2 weeks	Level III
	Erythromycin [22, 129]	200 mg 4 times daily	2 weeks	Level II
	Acyclovir [141]	400 mg 3–5 times daily	1 week	Level I
	Phototherapy [135, 139]	10–20 J/cm2 to 30 J/cm2 for UV-A1 250 mJ/cm for NB-UVB	2–3 × week 3 × week	Level II

PRN as needed; NB-UVB narrowband ultraviolet B

^aThe graded levels of evidence are defined as follows: level I represents evidence from systematic reviews or meta-analyses of randomized controlled trials, level II represents evidence from randomized controlled trials, and level III represents evidence from non-randomized controlled trials

Limitations

While this review provides a comprehensive analysis of the clinical features and differential diagnoses of pityriasis rosea (PR), it is subject to some limitations. The review relies on the available literature, and variations in study quality, sample sizes, and geographic differences may limit the generalizability of the conclusions. Additionally, publication bias may have led to an overrepresentation of unusual or positive findings. We also did not perform a systematic meta-analysis, which limits the ability to quantitatively synthesize the data. As PR research evolves, more rigorous studies and controlled trials are needed to further refine our understanding.

Conclusions

Pityriasis rosea (PR) is a common dermatological condition with a distinct clinical presentation, yet its etiology remains elusive. Further research is needed to elucidate the precise etiological factors, particularly the role of viral reactivation and immune response mechanisms. Additionally, exploring the efficacy and safety of various treatment modalities, including antivirals and phototherapy, could enhance management strategies for PR, especially in atypical or recurrent cases. Understanding these aspects will be crucial for improving patient outcomes and developing targeted therapies.

Declarations

Funding

None.

Conflict of interest

None to declare for Kayla Mashoudy, Sarah Kim, Leah Farhadi, or Scott Elman.

Ethical approval

Not applicable.

Patient consent to participate/publish

Patients signed informed consent regarding publishing their data and photographs.

Data availability statement

The data analyzed in this review article are sourced from previously published studies and are accessible through the cited references. No new data was generated for this review.

Code availability

Not applicable.

Author contribution

Kayla Mashoudy: conceptualization, methodology, writing—original and final draft preparation; Sarah Kim: material preparation, writing—original draft preparation; Leah Farhadi: material preparation, writing—original draft preparation; Scott Elman: supervision, writing, and manuscript review. All authors read and approved the final manuscript.