To the Editor: We appreciate the article from Bitar et al1 on ibrutinib-associated pityriasis rosea (PR)-like rash that allows us to share our experience and make some observations. Recently, we proposed criteria to distinguish PR from PR-like eruptions (Table I). In fact, distinguishing them is of paramount importance, as a typical PR may develop during but independently from a therapy.2, 3 During PR, a self-limiting exanthematous disease associated with the endogenous systemic reactivation of human herpes virus (HHV)-6 and/or HHV-7, the drug (if indispensable for the health of the patient and except for immunosuppressive therapies that can favor viral reactivation) may be cautiously continued.4 When the skin rash is diagnosed as a drug reaction with morphological features similar to genuine PR (a PR-like eruption), it is preferable to stop the drug immediately to prevent more dangerous drug reactions. Indeed, the interesting case described by Bitar et al1 has some of the characteristics of PR-like eruptions such as the presence of itch on the lesions, the dusky-red color of the lesions, and the superficial and perivascular eosinophil infiltration in the dermis. However, it is uncommon after several months to have resolution of the eruption without interruption of the drug. In fact, this course of the disease is more typical for PR.4 Unfortunately, the authors have not investigated potential signs of HHV-6 and HHV-7 reactivation such as detection of HHV 6/7 DNA in plasma and detection of positive IgM antibodies against HHV-6/7 in serum. In addition, they did not refer to peripheral eosinophilia that may be a marker for adverse cutaneous drug reactions.5 These data would have been useful to better define the diagnosis: in presence of HHV-6 or HHV-7 reactivation addressing toward PR and, conversely, in presence of peripheral blood eosinophilia toward PR-like eruption caused by ibrutinib.
Table I.
| Classic PR | PR-like eruption | |
|---|---|---|
| Pathogenesis | Sporadic HHV-6/7 systemic reactivation | Reaction to a drug/vaccine |
| Morphology of the lesions | Finely scaling erythematous macules and/or plaques | Dusky-red macules and/or plaques with possible desquamation |
| Distribution | Involvement of the trunk and limbs (face spared): lesions symmetrically oriented with their long axes along the cleavage lines (theater curtain distribution) | Diffuse and confluent lesions on trunk, limbs and face |
| Oral mucosa involvement | Possible (16% of cases) | Possible (50% of cases) |
| Herald patch | Present (12%-90% of cases) | Absent |
| Itch | Absent or mild | Intense |
| Prodromal symptoms | Present (>69% of cases) | Absent |
| Laboratory exams | Within normal ranges | Possible peripheral eosinophilia (42% of cases) |
| Virologic investigations | 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. | No signs of HHV-6 and HHV-7 systemic reactivation |
| Histopathology | Parakeratosis, spongiosis (epidermis); extravasated red blood cells, lymphocyte infiltrate (dermis) | Interface dermatitis and eosinophils |
| Therapeutic options | Bed rest | Drug withdrawal |
| Mean duration | 45 day | 14 days after discontinuing the drug |
Footnotes
Funding sources: None.
Conflicts of interest: None disclosed.
References
- 1.Bitar C., Sadeghian A., Sullivan L. Ibrutinib-associated pityriasis rosea-like rash. JAAD Case Rep. 2017;4:55–57. doi: 10.1016/j.jdcr.2017.06.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Drago F., Broccolo F., Agnoletti A. Pityriasis rosea and pityriasis rosea-like eruptions. J Am Acad Dermatol. 2014;70:196. doi: 10.1016/j.jaad.2013.08.056. [DOI] [PubMed] [Google Scholar]
- 3.Drago F., Ciccarese G., Rebora A. Pityriasis rosea and pityriasis rosea-like eruption: can they be distinguished? J Dermatol. 2014;41:864–865. doi: 10.1111/1346-8138.12562. [DOI] [PubMed] [Google Scholar]
- 4.Drago F., Ciccarese G., Rebora A. Pityriasis rosea: a comprehensive classification. Dermatology. 2016;232:431–437. doi: 10.1159/000445375. [DOI] [PubMed] [Google Scholar]
- 5.Drago F., Cogorno L., Agnoletti A.F. A retrospective study of cutaneous drug reactions in an outpatient population. Int J Clin Pharm. 2015;37:739–743. doi: 10.1007/s11096-015-0134-z. [DOI] [PubMed] [Google Scholar]