LETTERS NOTES
& COMMENTS
Pityriasis rosea and pityriasis roseaelike eruptions To the Editor: We read with great interest the case of pityriasis rosea (PR)elike eruption associated with lamotrigine by Papadavid et al.1 This article may raise the issue of why a drug eruption presents with clinical features that strikingly resemble genuine PR. It may be speculated that the drug could have triggered human herpesvirus (HHV) 6 and/or HHV 7, recently implicated in the pathogenesis of PR,2-4 to abandon their latency and to reactivate. This phenomenon has been demonstrated in drug reactions associated with eosinophilia and systemic symptoms (DRESS).5 Our experience, however, seems to disprove such a hypothesis. In fact, we studied 12 patients with PR-like eruptions from a clinical, histopathologic, and virologic point of view. The eruptions followed, without a definite interval, a lesion resembling the herald patch in only 3 cases. Lesions were more confluent than in typical PR, they involved the limbs more extensively, in 2 cases the face, in 6 cases the mucous membranes (mouth and tongue), and caused excessive itching. No patient experienced prodromal symptoms. Five patients had a slight blood eosinophilia. Histopathology was studied in 9 patients showing eosinophils in the dermis in all cases, a perivascular infiltrate in 7 cases, necrotic keratinocytes within the epidermis in 8 cases, and signs of junctional vacuolar degeneration in 7 cases. All the patients recovered 2 weeks after discontinuing the drug, which is less than it takes for typical PR. In 10 patients we searched for HHV 6 and HHV 7 DNA in plasma and blood mononuclear cells, by calibrated quantitative real-time polymerase chain reaction as previously described.3 HHV 6 DNA, a marker of active infection, was detected in the plasma of only 1 patient. We hypothesize that the clinical and histopathologic features and, above all, the virologic investigations, may help to distinguish typical PR from PR-like eruptions, although, considering our small series of patients, further studies are needed. Francesco Drago, MD,a Francesco Broccolo, MD,b Arianna Agnoletti, MD,a Francesca Drago,a Alfredo Rebora, MD,a and Aurora Parodi, MDa DISSAL Section of Dermatology IRCCS Azienda Universitaria Ospedaliera San Martino-IST, Genoa,a and Department of Clinical Medicine 196
JANUARY 2014
and Prevention, University of Milano-Bicocca, Monza,b Italy Funding sources: None. Conflicts of interest: None declared. Correspondence to: Arianna Agnoletti, MD, DISSAL Section of Dermatology IRCCS Azienda Universitaria Ospedaliera San Martino-IST, Viale Benedetto XV, 5, Genoa, 16132, Italy E-mail: [email protected] REFERENCES 1. Papadavid E, Panayiotides I, Makris M, Giatrakou S, Dalamaga M, Nikolaos S, et al. Pityriasis roseaelike eruption associated with lamotrigine. J Am Acad Dermatol 2013;68:e180-1. 2. Drago F, Ranieri E, Malaguti F, Losi E, Rebora A. Human herpesvirus 7 in pityriasis rosea. Lancet 1997;349:1367-8. 3. Broccolo F, Drago F, Careddu AM, Foglieni C, Turbino L, Cocuzza CE, et al. Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 2005;124:1234-40. 4. Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its herpesvirus origin. J Am Acad Dermatol 2009;61:303-18. 5. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome. J Am Acad Dermatol 2013;68:693.e1-14. http://dx.doi.org/10.1016/j.jaad.2013.08.056
Reply to: Pityriasis rosea and pityriasis roseaelike eruptions To the Editor: We appreciate the interest of Drago and colleagues in our article and we are pleased that they present their cases of pityriasis rosea (PR) and PR-like eruptions. However, we would like to respond with 2 short comments as follows: 1. Herpesviruses are highly adapted to lifelong infection of their human hosts and thus can be considered a component of the human ‘‘microbiome’’ in addition to their role in illness.1 Herpesvirus reactivation (especially human herpesvirus [HHV] 6 and HHV 7) has been demonstrated in drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.2,3 A viral origin in PR has been suggested, with HHV being the most likely etiological agent according to studies,4 including those by Drago et al.5 Our case does not fulfill the criteria of DRESS but represents a well-documented case of PR-like drug-induced exanthema associated with adenopathy. We do not propose a J AM ACAD DERMATOL
J AM ACAD DERMATOL
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pathogenic mechanism but emphasize the possible role of HHV 6 and HHV 7 in this PR-like eruption. 2. The number of patients with PR-like eruptions is too small to reach conclusions. In our opinion, the finding of 1 of 10 (10%) HHV 6 activation in this sample cannot either support or disprove any hypothesis. Evangelia Papadavid, MD, PhD,a Ioannis Panayiotides, MD, PhD,b Maria Dalamaga, MD, PhD,c Sophia Giatrakou, MD,a Nikolaos Stavrianeas, MD, PhD,a Dimitrios Rigopoulos, MD, PhD,a and Michael Makris, MD, PhDa Second Department of Dermatology and Allergy Unit D Kalogeromitros,a Second Department of Pathology,b and Department of Clinical Biochemistry,c Athens University Medical School, Attikon University General Hospital, Athens, Greece Funding sources: None. Conflicts of interest: None declared. Correspondence to: Evangelia Papadavid, MD, PhD, Second Department of Dermatology and Allergy Unit D. Kalogeromitros, Attikon General University Hospital, Rimini 1, Haidari, 12462, Athens, P.O. 12464, Greece E-mail: [email protected] REFERENCES 1. Dreyfus DH. Herpes viruses and the microbiome. J Allergy Clin Immunol doi: 10.1016/j.jaci.2013.02.039. Published online April 20, 2013. 2. Hamaguchi Y, Fujimoto M, Enokido Y, Wayaku T, Kaji K, Echigo T, et al. Intractable genital ulcers from herpes simplex virus reactivation in drug-induced hypersensitivity syndrome caused by allopurinol. Int J Dermatol 2010;49:700-4. 3. Morito H, Kitamura K, Fukumoto T, Kobayashi N, Kuwahara M, Asada H. Drug eruption with eosinophilia and systemic symptoms associated with reactivation of human herpesvirus 7, not human herpesvirus 6. J Dermatol 2012;39:669-70. 4. Vag T, Sonkoly E, Kemery B, Ongradi J. Avidity of antibodies to HHV-7 suggests primary infection in young adults with pityriasis rosea. J Eur Acad Dermatol Venereol 2004;18:738-40. 5. Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its herpesvirus origin. J Am Acad Dermatol 2009;61:303-18. http://dx.doi.org/10.1016/j.jaad.2013.09.033
Pityriasis rosea and activation of latent herpesvirus infections To the Editor: The comments of Professor Drago and associates1 concerning pityriasis rosea (PR), PR-like drug eruptions, and herpesvirus infections
are noteworthy.2,3 The concept of a chronic persistent herpesvirus infection becoming active to cause or exacerbate disease is an intriguing one, with the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and Kaposi sarcoma representing salient examples.4,5 Clearly, activating a lifelong latent herpesvirus infection may have substantial consequences. Clinical and histopathologic features do help to distinguish typical PR from PR-like eruptions.6 Virologic investigations for herpesvirus 6 and 7 may as well,1 but are less likely to be practical even if they prove helpful. Robert A. Schwartz, MD, MPH, DSc (Hon), FRCP Edin, and W. Clark Lambert, MD, PhD Rutgers University New Jersey Medical School, Newark Funding sources: None. Conflicts of interest: None declared. Correspondence to: Robert A. Schwartz, MD, MPH, DSc (Hon), FRCP Edin, Rutgers University New Jersey Medical School, 185 S Orange Ave, MSB H-576, Newark, NJ 07103-2714. E-mail: [email protected] REFERENCES 1. Drago F, Broccolo F, Agnoletti A, Drago F, Rebora A, Parodi A. Pityriasis rosea and pityriasis rosea-like eruptions. J Am Acad Dermatol 2013;70:196. 2. Evangelia P, Ioannis P, Michael M, Sophia G, Maria D, Stavrianeas N, et al. Pityriasis rosea-like eruption associated with lamotrigine. J Am Acad Dermatol 2013;68:e180-1. 3. Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its herpesvirus origin. J Am Acad Dermatol 2009;61:303-18. 4. Schwartz RA, Micali G, Nasca MR, Scuderi L. Kaposi’s sarcoma: a continuing conundrum. J Am Acad Dermatol 2008;59: 179-206. 5. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome, part I: clinical perspectives. J Am Acad Dermatol 2013;68: 693-705. 6. Gonzalez L, Allen RA, Janniger CK, Schwartz RA. Pityriasis rosea: an important papulosquamous disorder. Int J Dermatol 2005;44:757-64. http://dx.doi.org/10.1016/j.jaad.2013.09.032
Letter to the editor To the Editor: We read with interest Shah et al’s recent detailed review of the cutaneous findings associated with the hereditary and nonhereditary polyposis disorders and paraneoplastic disorders.1 We found the images to be quite instructive. However, we wonder whether Fig 4, A (Cowden
& COMMENTS
Pityriasis rosea and pityriasis roseaelike eruptions To the Editor: We read with great interest the case of pityriasis rosea (PR)elike eruption associated with lamotrigine by Papadavid et al.1 This article may raise the issue of why a drug eruption presents with clinical features that strikingly resemble genuine PR. It may be speculated that the drug could have triggered human herpesvirus (HHV) 6 and/or HHV 7, recently implicated in the pathogenesis of PR,2-4 to abandon their latency and to reactivate. This phenomenon has been demonstrated in drug reactions associated with eosinophilia and systemic symptoms (DRESS).5 Our experience, however, seems to disprove such a hypothesis. In fact, we studied 12 patients with PR-like eruptions from a clinical, histopathologic, and virologic point of view. The eruptions followed, without a definite interval, a lesion resembling the herald patch in only 3 cases. Lesions were more confluent than in typical PR, they involved the limbs more extensively, in 2 cases the face, in 6 cases the mucous membranes (mouth and tongue), and caused excessive itching. No patient experienced prodromal symptoms. Five patients had a slight blood eosinophilia. Histopathology was studied in 9 patients showing eosinophils in the dermis in all cases, a perivascular infiltrate in 7 cases, necrotic keratinocytes within the epidermis in 8 cases, and signs of junctional vacuolar degeneration in 7 cases. All the patients recovered 2 weeks after discontinuing the drug, which is less than it takes for typical PR. In 10 patients we searched for HHV 6 and HHV 7 DNA in plasma and blood mononuclear cells, by calibrated quantitative real-time polymerase chain reaction as previously described.3 HHV 6 DNA, a marker of active infection, was detected in the plasma of only 1 patient. We hypothesize that the clinical and histopathologic features and, above all, the virologic investigations, may help to distinguish typical PR from PR-like eruptions, although, considering our small series of patients, further studies are needed. Francesco Drago, MD,a Francesco Broccolo, MD,b Arianna Agnoletti, MD,a Francesca Drago,a Alfredo Rebora, MD,a and Aurora Parodi, MDa DISSAL Section of Dermatology IRCCS Azienda Universitaria Ospedaliera San Martino-IST, Genoa,a and Department of Clinical Medicine 196
JANUARY 2014
and Prevention, University of Milano-Bicocca, Monza,b Italy Funding sources: None. Conflicts of interest: None declared. Correspondence to: Arianna Agnoletti, MD, DISSAL Section of Dermatology IRCCS Azienda Universitaria Ospedaliera San Martino-IST, Viale Benedetto XV, 5, Genoa, 16132, Italy E-mail: [email protected] REFERENCES 1. Papadavid E, Panayiotides I, Makris M, Giatrakou S, Dalamaga M, Nikolaos S, et al. Pityriasis roseaelike eruption associated with lamotrigine. J Am Acad Dermatol 2013;68:e180-1. 2. Drago F, Ranieri E, Malaguti F, Losi E, Rebora A. Human herpesvirus 7 in pityriasis rosea. Lancet 1997;349:1367-8. 3. Broccolo F, Drago F, Careddu AM, Foglieni C, Turbino L, Cocuzza CE, et al. Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7. J Invest Dermatol 2005;124:1234-40. 4. Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its herpesvirus origin. J Am Acad Dermatol 2009;61:303-18. 5. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome. J Am Acad Dermatol 2013;68:693.e1-14. http://dx.doi.org/10.1016/j.jaad.2013.08.056
Reply to: Pityriasis rosea and pityriasis roseaelike eruptions To the Editor: We appreciate the interest of Drago and colleagues in our article and we are pleased that they present their cases of pityriasis rosea (PR) and PR-like eruptions. However, we would like to respond with 2 short comments as follows: 1. Herpesviruses are highly adapted to lifelong infection of their human hosts and thus can be considered a component of the human ‘‘microbiome’’ in addition to their role in illness.1 Herpesvirus reactivation (especially human herpesvirus [HHV] 6 and HHV 7) has been demonstrated in drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.2,3 A viral origin in PR has been suggested, with HHV being the most likely etiological agent according to studies,4 including those by Drago et al.5 Our case does not fulfill the criteria of DRESS but represents a well-documented case of PR-like drug-induced exanthema associated with adenopathy. We do not propose a J AM ACAD DERMATOL
J AM ACAD DERMATOL
Letters 197
VOLUME 70, NUMBER 1
pathogenic mechanism but emphasize the possible role of HHV 6 and HHV 7 in this PR-like eruption. 2. The number of patients with PR-like eruptions is too small to reach conclusions. In our opinion, the finding of 1 of 10 (10%) HHV 6 activation in this sample cannot either support or disprove any hypothesis. Evangelia Papadavid, MD, PhD,a Ioannis Panayiotides, MD, PhD,b Maria Dalamaga, MD, PhD,c Sophia Giatrakou, MD,a Nikolaos Stavrianeas, MD, PhD,a Dimitrios Rigopoulos, MD, PhD,a and Michael Makris, MD, PhDa Second Department of Dermatology and Allergy Unit D Kalogeromitros,a Second Department of Pathology,b and Department of Clinical Biochemistry,c Athens University Medical School, Attikon University General Hospital, Athens, Greece Funding sources: None. Conflicts of interest: None declared. Correspondence to: Evangelia Papadavid, MD, PhD, Second Department of Dermatology and Allergy Unit D. Kalogeromitros, Attikon General University Hospital, Rimini 1, Haidari, 12462, Athens, P.O. 12464, Greece E-mail: [email protected] REFERENCES 1. Dreyfus DH. Herpes viruses and the microbiome. J Allergy Clin Immunol doi: 10.1016/j.jaci.2013.02.039. Published online April 20, 2013. 2. Hamaguchi Y, Fujimoto M, Enokido Y, Wayaku T, Kaji K, Echigo T, et al. Intractable genital ulcers from herpes simplex virus reactivation in drug-induced hypersensitivity syndrome caused by allopurinol. Int J Dermatol 2010;49:700-4. 3. Morito H, Kitamura K, Fukumoto T, Kobayashi N, Kuwahara M, Asada H. Drug eruption with eosinophilia and systemic symptoms associated with reactivation of human herpesvirus 7, not human herpesvirus 6. J Dermatol 2012;39:669-70. 4. Vag T, Sonkoly E, Kemery B, Ongradi J. Avidity of antibodies to HHV-7 suggests primary infection in young adults with pityriasis rosea. J Eur Acad Dermatol Venereol 2004;18:738-40. 5. Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its herpesvirus origin. J Am Acad Dermatol 2009;61:303-18. http://dx.doi.org/10.1016/j.jaad.2013.09.033
Pityriasis rosea and activation of latent herpesvirus infections To the Editor: The comments of Professor Drago and associates1 concerning pityriasis rosea (PR), PR-like drug eruptions, and herpesvirus infections
are noteworthy.2,3 The concept of a chronic persistent herpesvirus infection becoming active to cause or exacerbate disease is an intriguing one, with the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and Kaposi sarcoma representing salient examples.4,5 Clearly, activating a lifelong latent herpesvirus infection may have substantial consequences. Clinical and histopathologic features do help to distinguish typical PR from PR-like eruptions.6 Virologic investigations for herpesvirus 6 and 7 may as well,1 but are less likely to be practical even if they prove helpful. Robert A. Schwartz, MD, MPH, DSc (Hon), FRCP Edin, and W. Clark Lambert, MD, PhD Rutgers University New Jersey Medical School, Newark Funding sources: None. Conflicts of interest: None declared. Correspondence to: Robert A. Schwartz, MD, MPH, DSc (Hon), FRCP Edin, Rutgers University New Jersey Medical School, 185 S Orange Ave, MSB H-576, Newark, NJ 07103-2714. E-mail: [email protected] REFERENCES 1. Drago F, Broccolo F, Agnoletti A, Drago F, Rebora A, Parodi A. Pityriasis rosea and pityriasis rosea-like eruptions. J Am Acad Dermatol 2013;70:196. 2. Evangelia P, Ioannis P, Michael M, Sophia G, Maria D, Stavrianeas N, et al. Pityriasis rosea-like eruption associated with lamotrigine. J Am Acad Dermatol 2013;68:e180-1. 3. Drago F, Broccolo F, Rebora A. Pityriasis rosea: an update with a critical appraisal of its herpesvirus origin. J Am Acad Dermatol 2009;61:303-18. 4. Schwartz RA, Micali G, Nasca MR, Scuderi L. Kaposi’s sarcoma: a continuing conundrum. J Am Acad Dermatol 2008;59: 179-206. 5. Husain Z, Reddy BY, Schwartz RA. DRESS syndrome, part I: clinical perspectives. J Am Acad Dermatol 2013;68: 693-705. 6. Gonzalez L, Allen RA, Janniger CK, Schwartz RA. Pityriasis rosea: an important papulosquamous disorder. Int J Dermatol 2005;44:757-64. http://dx.doi.org/10.1016/j.jaad.2013.09.032
Letter to the editor To the Editor: We read with interest Shah et al’s recent detailed review of the cutaneous findings associated with the hereditary and nonhereditary polyposis disorders and paraneoplastic disorders.1 We found the images to be quite instructive. However, we wonder whether Fig 4, A (Cowden
