PR vs PRLE
PITYRIASIS ROSEA AND PITYRIASIS ROSEA-LIKE ERUPTIONS: A CHRISTMAS TALE
By Warren R. Heymann, MD, FAAD
Dec. 3, 2025
Vol. 7, No. 47
Drago et al. expertly summarized clinical, histopathologic, and viral criteria to distinguish PR from PRLE. 1) Pathogenesis — PR (Sporadic HHV-6/7 systemic reactivation) versus PRLE (Reaction to a drug or vaccine); 2) Prodromal symptoms — PR (Present in > 69% of cases) versus PRLE (Absent); 3) Herald patch — PR (Present in 12 -90% of cases) versus PRLE (Absent); 4) Pruritus — PR (absent or mild) versus (Intense) 5) Morphology — PR (Finely scaling erythematous macules and/or plaques) versus PRLE (Dusky-red macules and/or plaques with possible desquamation); 6) Distribution — PR (Involvement of the trunk and limbs sparing the face [my former chair of dermatology Michael Fisher called this the "long turtle neck, short sleeve" distribution] with lesions symmetrically oriented with their long axes along the cleavage lines (theater curtain distribution [aka "Christmas tree" distribution]) versus PRLE (Diffuse and confluent lesions on trunk, limbs and face); 7) Oral mucosa involvement — PR (Possible, noted in16% of cases) versus PRLE (Possible in 50% of cases); 8) Laboratory exams [Complete Blood Count] — PR (normal) versus PRLE (Possible peripheral eosinophilia in 42% of cases); 9) Virilogic investigations — PR (Signs of HHV-6 and/or HHV-7 systemic reactivation; detection of HHV 6/7 DNA in plasma and peripheral blood mononuclear cells; detection of positive IgM antibodies against HHV-6/7 in serum) vs PRLE (No signs of HHV-6 and HHV-7 systemic reactivation); 10) Histopathology — PR (Parakeratosis, spongiosis (epidermis); extravasated red blood cells, dermal lymphocytic infiltrate) versus PRLE (Interface dermatitis and eosinophils); 10) Therapeutic options — PR (bed rest [topical steroids, narrow band phototherapy, possibly acyclovir]) versus PRLE (Drug withdrawal [topical or systemic steroids]; 11) Mean duration — PR (45 days) versus PRLE (14 days after discontinuation of the culprit drug). (1)
Two case reports of PRLE due to imatinib in septuagenarian men with chronic myelogenous leukemia emphasize two distinct teaching points. 1) Numerous necrotic keratinocytes, interface dermatitis, and eosinophils support the diagnosis of PRLE over PR. (6) 2) PRLE may recur with drug readministration. Notably, there was no recurrence when the patient was switched to dasatinib, suggesting that a PRLE is not exclusively a drug class effect. (7)
Vaccinations may be associated with a PRLE. Khan et al. systematically reviewed 111 people who developed PR or a PRLE after COVID-19 vaccination. Sixty-five patients (58.5%) received an mRNA vaccine (Pfizer or Moderna). The average age of incidence was 44.92 years, 36 (55.38%) women, and 63 (62.37%) of patients presented after administration of the first dose. Most cases were asymptomatic or displayed mild symptoms. Compared to other vaccines that have been reported to cause PRLE (tuberculosis, smallpox, diphtheria, influenza, diphtheria‐pertussis‐tetanus, influenza A, tetanus, pneumococcus, papillomaviruses, hepatitis B, and yellow fever) typically appearing within 5-7 days of administration, the time of onset after COVID‐19 vaccines ranged from 24 hours to 30 days, with a mean time of 8.58 days. (8)
In their editorial on maculopapular eruptions following COVID-19 vaccination, Ciccarese et al. conclude, "the distinction between PR and PR-like is relevant mainly for prognostic purposes. Indeed, regarding vaccine related-PR, which lasts on average 45 days, it is unlikely that HHV-6/7 reactivation occurs again following the booster dose. Conversely, the vaccine-related-PR-LE is a hypersensitivity reaction, such as a drug-related one, and, therefore, it is less predictable in its course. Usually, after the vaccine dose or after drug withdrawal, it lasts on average 2 weeks, and after a booster dose, as well as if the offending drug is restarted, the skin eruption may not recur, or may recur with more severe features, differing in morphology and distribution of the eruption and, sometimes, presenting with systemic symptoms." (9) Prospective studies are warranted to understand the relationship between COVID-19 and PRLE, but in the interim, I suggest that my patients receive their boosters. This approach concurs with Elyoussfi and Coulson, who state "Unlike anaphylaxis, cutaneous adverse reactions alone are not a contraindication to re-vaccination. The available evidence supports that cutaneous reactions to COVID-19 vaccination are generally minor, self-limiting, and should not discourage vaccination." (10)
Point to Remember: Based on clinical, histologic, and laboratory criteria, pityriasis rosea may reliably be differentiated from pityriasis rosea-like eruptions caused by drugs, herbs, infections, or vaccinations.
Our expert's viewpoint
Giulia Ciccarese, MD, PhD
Department of Medical and Surgical Sciences, University of Foggia, Italy
Francesco Drago
Clinic Villa Montallegro, Genoa, Italy
In his commentary on Pityriasis Rosea (PR) and Pityriasis Rosea-Like Eruptions (PR-LE), Dr. Heymann thoroughly listed and explained the differences between these two conditions, which are frequently encountered in dermatological clinical practice. Although clinically distinguishing the two eruptions is often tricky, PR and PR-LE have distinct pathogenetic mechanisms, courses, and prognoses, necessitating different management approaches. Broadly, PR-LE is a drug or vaccine-induced skin eruption that can be compared to PR just as morbilliform drug eruptions to measles. Conversely, a typical PR may develop during but regardless of ongoing therapy.
From a practical viewpoint, it is essential to distinguish between the two forms, as the management differs, and knowing when to stop the involved drug may be of paramount importance.
We previously proposed clinical, laboratory, and histological criteria to help dermatologists and other specialists differentiate between the two entities. (11)
When faced with a skin eruption resembling PR, the physician should evaluate the patient's recent medical and pharmacological history. Indeed, PR is an acute, self-limiting exanthem associated with the systemic endogenous reactivation of human herpesvirus (HHV)-6 and (HHV)-7; therefore, conditions of psychological stress, temporary states of altered immunological response (e.g., during pregnancy or after surgery) or true immunosuppression (e.g., associated with SARS-CoV-2 infection or during oncological diseases, transplants, or treatment with immunosuppressants), may act enabling the reactivation of these latent viral infections. In contrast, PR-LE is a drug-induced or vaccine-induced skin eruption that usually does not involve HHV-6 and HHV-7.
Accordingly, prodromal flu-like symptoms such as general malaise, fatigue, headache, gastrointestinal/upper respiratory symptoms, and mild fever often precede the eruption in PR. In contrast, they are usually absent in PR-LE. Just a few prodromal symptoms (low fever and chills) for a couple of days may be present in PR-LE after administering a vaccine.
Beyond these clinical criteria, we also proposed some laboratory, virologic, and histologic criteria for distinguishing between the two forms. Routine laboratory findings are within normal ranges in PR and virological investigations detect the presence of HHV-6/HHV-7 DNA in plasma, a marker of active infection. Furthermore, serology may disclose IgM antibodies against HHV-6 or HHV-7. Conversely, in PR-LE, peripheral eosinophilia, which occurs frequently and represents a marker for adverse cutaneous drug reactions, may be found (42%). At the same time, no signs of HHV-6/HHV-7 systemic reactivation in the plasma are detected.
The histopathology also differs: PR shows epidermal focal parakeratosis and spongiosis, scattered dyskeratotic keratinocytes, extravasated red blood cells, and dermal perivascular infiltrate of lymphocytes and histiocytes. In PR-LE, the histologic features of an adverse drug reaction are evident: interface dermatitis with individual necrotic keratinocytes, diffuse perivascular infiltrate of lymphocytes, histiocytes, and eosinophils in the dermis, and enlargement of endothelial cells.
The duration of the skin eruption is also very different between the two conditions: PR lasts on average 45 days, whereas PR-LE lasts about 2 weeks after drug discontinuation or vaccine administration.
The management of the two skin eruptions depends on the diagnosis: PR is a self-limiting rash that gradually resolves without leaving any sequelae. Thus, the best approach is to reassure the patient and recommend rest. Only in atypical PR cases characterized by extensive, persistent lesions and systemic symptoms that may affect the patient's quality of life should treatment be considered. A recent meta-analysis on the comparative efficacy of various pharmacological treatments for PR indicated that oral Acyclovir (800 mg five times daily for seven days) is the most effective option for patients with extensive, persistent lesions or systemic symptoms. (12) In PR-LE, the management consists of immediate drug withdrawal or replacement to prevent more dangerous and life-threatening drug reactions. Notably, whether a typical PR develops during a therapy, the drug/drugs (if indispensable for the patient's health) may be cautiously continued. Extreme caution should be observed in the case of patients under treatment with immunosuppressors, which can favour viral reactivation.
Concerning the skin eruptions that may develop following vaccine administration, it is unlikely that HHV-6 and HHV-7 reactivation — and therefore classic PR — will occur again after the booster dose. Conversely, PR-LE represents a less predictable hypersensitivity reaction. With booster doses, the clinical manifestation may not recur or may differ from PR-LE, potentially also presenting with systemic symptoms. However, the possibility of mild and self-limiting cutaneous adverse events should not discourage the eligible candidates from receiving the scheduled vaccinations.
In conclusion, we emphasize distinguishing between PR and PR-LE to achieve an accurate diagnosis and optimal patient management. When clinical features are not sufficiently distinctive, investigating HHV-6 and HHV-7 reactivations is crucial for diagnostic purposes. Furthermore, in the event of associated diseases, their reactivation may contribute to the patient's systemic inflammation and ultimately impact the disease's progression.
PR vs. PR-LE
| Typical PR | PR-LE | |
|---|---|---|
Pathogenesis | HHV-6/HHV-7 endogenous systemic reactivation | Adverse reaction to a drug/vaccine |
Prodromal symptoms | Often present (>69%) | Absent |
Herald patch | Present (12-90%) | Absent |
Morphology of the lesions | Finely scaling erythematous macules, papules, plaques | Dusky-red macules and/or plaques |
Distribution of the lesions | Lesions symmetrically oriented with their long axes along the cleavage lines on the trunk | Diffuse and confluent lesions on trunk, limbs and face |
Oropharyngeal involvement | Occasional (16%) | Often (50%) |
Pruritus | Absent / mild | Present |
Laboratory investigations | Within normal ranges | Peripheral eosinophilia (42% of cases) |
Virologic investigations | Detection of HHV 6/7 DNA in Plasma; IgM antibodies against HHV-6/7 in serum | No signs of HHV-6 and HHV-7 reactivation in plasma |
Histopathology | Epidermal focal parakeratosis and spongiosis; few dyskeratotic keratinocytes; extravasated red blood cells and perivascular Infiltrate of lymphocytes, histiocytes in the dermis | Interface dermatitis with scattered single necrotic keratinocytes; diffuse perivascular infiltrate of lymphocytes, histiocytes, and eosinophils in the dermis; enlargement of endothelial cells |
Duration | 45 days | 14 days after stopping the drug / vaccine adrministration |
Therapy | Rest | Drug withdrawal |
References
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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posted by dermatica at
December 05, 2025
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