Treatment of Psychiatric Disorders and Skin-Restricted Lupus Remission

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Treatment of Psychiatric Disorders and

Skin-Restricted Lupus Remission:

A Longitudinal Study

Skin-restricted lupus erythematosus (SRL) comprises discoid lupus erythematosus (DLE), lupus tumidus (LT), and sub-acute cutaneous lupus erythematosus (SCLE). We and others reported a high prevalence of psychiatric disorders (PD), of-ten undertreated, in patients with SRL.1,2

However, the im-pact of PDs and psychotropic medications on skin disease out-come has not been described. Thus, we decided to investigate this relationship in a patient cohort over 2.5 years.

Methods|After providing written informed consent, 75 pa-tients with DLE, LT, or SCLE, prospectively recruited, were as-sessed by a dermatologist and a psychiatrist every 6 months over 2.5 years. The dermatologist recorded whether the SRL was in remission as defined by the complete absence of in-flammatory lesions. More details can be found in previous article.1

This study received approval from the local ethical re-view board.

To assess the relationship between SRL remission and cur-rent psychiatric factors, we compared patients according to re-mission or not in univariate analysis, taking 1 assessment as the statistical unit because patient status for SRL remission, PD presence, and use of psychotropic medications may change during the study. A conditional inference tree (Figure) was built and plotted to illustrate the associations in a nonparametric manner. All displayed P values are Bonferroni corrected. We then used a multilevel mixed model and adjusted for the pres-ence of PDs and treatments to take into account repetitive evaluations for each patient. All P values (2 sided) less than .05 were considered statistically significant.

Results|Overall, 313 assessments were made (4.2 per patient); 47 patients (63%) underwent the 5 assessments

and 56 patient (75%) underwent at least 4. After exclusion of incomplete assessments, the data of 292 assessments were analyzed. The most discriminating factor for complete SRL remission was cigarette smoking. However, because of its strong association with SRL and PDs, we decided to look beyond this factor and performed the analysis for the condi-tional inference tree (Figure, A). A history of suicide attempt was identified as the second discriminating factor; psycho-tropic medication was identified as the third discriminating factor.

Thus, we focused attention on patients with PD (Figure, B). During follow-up, 43 patients had at least 1 assessment with a PD. In these assessments, psychotropic medications were associated with SRL remission (odds ratio, 2.5; 95% CI, 1.1-5.6; P = .02). To take into account the patient effect, a multivariate analysis of lupus remission was performed (Table). The presence of PDs tended to decrease the chances of SRL remission while psychotropic treatments appeared to increase them.

Discussion|To our knowledge, our study is the first to assess the clinical and therapeutic psychiatric factors associated with SRL remission.

First, smoking is a factor of poor prognosis in SRL in agreement with actions of tobacco consumption in the SRL pathogenesis.

Second, a history of attempted suicide is associated with a bad outcome of skin lesions, and psychotropic drugs help in achieving remission of SRL in patients with PDs. Patients with SRL who have attempted suicide could be less likely to com-ply with dermatological treatment owing to their negative health behaviors and PDs,1,3

while improvement in PDs treated by psychotropic medications could contribute to better com-pliance with SRL treatment.3_{Proinflammatory cytokines may} also be a contributory factor because the same cytokines are

Figure. Association of Psychotropic Medication and Lupus Remission

75 Patients with SRL 292 Assessments 0 100 80 Lupus R e mission, % 60 40 20 Assessments, No. 184 35% 87 52% 21 0% Discriminating factors for lupus remission

A Psychotropic medication (_{P = .02)} Suicide attempt (P = .004) Yes No Yes No

43 Patients with SRL and PD 187 Assessments 123 Assessments with PD 64 Assessments without PD 0 100 80 Lupus R e mission, % 60 40 20 Assessments, No. 59 33% 64 57% Lupus remission in patients with PD

B

Psychotropic medication (_{P = .02)}

No Yes

Decision trees illustrate (A) the most discriminating factors (beyond smoking) for lupus remission, and (B) lupus remission in patients with PD according to psychotropic medication status. PD indicates psychiatric disorder; SRL, skin-restricted lupus erythematosus.

Letters

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increased in patients with SRL who have attempted suicide4 and could be decreased by some antidepressants5

and benzodiazepines.6

Our study has some limitations. We did not use a vali-dated skin score and instead used SRL remission. Because of variations of patient status over 2.5 years, the analysis was based on assessments; we cannot discern whether psychiat-ric medications improve skin outcomes in an individual pa-tient. Nevertheless, dermatologists should be further encour-aged to identify PDs in patients with SRL because their treatment with psychotropic medications was associated with improved skin disease outcome.

Isabelle Jalenques, MD, PhD Fabien Rondepierre, PhD Catherine Massoubre, MD, PhD Bruno Labeille, MD Jean-Luc Perrot, MD Aurélien Mulliez, MSc Michel D’Incan, MD, PhD; for the LuPsy Cohort Investigators

Author Affiliations: Service de Psychiatrie de l'Adulte A et Psychologie médicale, CHU Ferrand, Université Clermont Auvergne, Clermont-Ferrand, France (Jalenques); Service de Psychiatrie de l'Adulte A et Psychologie médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France (Rondepierre); Service de Psychiatrie, CHU St-Etienne, University Jean Monnet, St-Etienne, France (Massoubre); Service de dermatologie, CHU Hopital Nord, Saint-Etienne, France (Labeille, Perrot); Direction de la Recherche Clinique et de l’Innovation, CHU Clermont Ferrand, Clermont-Ferrand, France (Mulliez); Service de Dermatologie, CHU Clermont-Ferrand, Université Clermont Auvergne, Clermont-Ferrand, France (D’Incan).

Corresponding Author: Isabelle Jalenques, MD, PhD, CHU Clermont-Ferrand, Service de Psychiatrie de l'Adulte A et Psychologie médicale, 58 rue Montalembert, 63003 Clermont-Ferrand, France (ijalenques@chu-clermontferrand.fr). Accepted for Publication: July 25, 2017.

Published Online: October 4, 2017. doi:10.1001/jamadermatol.2017.3590 Author Contributions Drs Jalenques and Rondepierre had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Jalenques, D’Incan.

Acquisition, analysis, or interpretation of data: Jalenques, Rondepierre, Massoubre, Labeille, Perrot, Mulliez.

Drafting of the manuscript: Jalenques, Rondepierre, D’Incan.

Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Rondepierre, Mulliez.

Obtained funding: Jalenques, D’Incan.

Administrative, technical, or material support: Rondepierre. Study supervision: Jalenques, Massoubre, Perrot.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by a grant from the French Ministry of Health (PHRC IR 2006 Jalenques, No. 2008-A00343-52) and from Société Française de Dermatologie, 2010.

Role of the Funder/Sponsor: The funder/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The LuPsy Cohort Investigators: François Aubin (Université de Franche Comté, CHU Besançon, Service de Dermatologie, Besançon, France), Christophe Bedane (Department of dermatology, Hopital Dupuytren, Limoges, France), Sophie Bonnefond (Urgences psychiatriques, Centre Hospitalier Esquirol, Limoges, France), Myriam Chastaing (Unité de Psychiatrie de Liaison et Service de Dermatologie, CHU Brest, Brest, France), Marianne Collange (Service de Psychiatrie de l'Adulte A et Psychologie médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France), Patrick Combemale, Denys Courbier (Hôpital d’instruction des armées Desgenettes, Lyon, France), Carole Durand (Service de Psychiatrie de l'Adulte A et Psychologie médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France), Jean Paul Grand (CHS Le Valmont, Urgences et Psychiatrie de Liaison, Hôpital Général de Valence, Valence, France), Emmanuel Haffen (Department of clinical psychiatry, INSERM, university hospital of Besançon, Besançon, France), Laurent Misery (University Hospital of Brest, Department of Dermatology and University of Western Brittany, Laboratory of Neurosciences of Brest, Brest, France), Anne Laure Pontonnier (Service de Psychiatrie de l'Adulte A et Psychologie médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France), (Robert Schwan (University Hospital of Psychiatrie and Psychotherapie, Laxou, France), François Skowron (Service de

dermatologie, CH de Valence, Valence, France), Agnès Sparsa (Service de Médecine Interne, Clinique Mutualiste Catalane, Perpignan, France), Gaëlle Theilhol (Service de Psychiatrie de l'Adulte A et Psychologie médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France), Julie Waton (Service de dermatologie, CHU de Nancy, Nancy, France).

Additional Contributions: We thank Silla Consoli for help in the preparation of the study design, the patients who participated in this study, and J. Watts for advice on the English version of the manuscript.

1. Jalenques I, Rondepierre F, Massoubre C, et al; Lupus Group. High prevalence of psychiatric disorders in patients with skin-restricted lupus: a case-control

study.Br J Dermatol. 2016;174(5):1051-1060.

2. Achtman J, Kling MA, Feng R, Okawa J, Werth VP. A cross-sectional study of untreated depression and anxiety in cutaneous lupus erythematosus and

dermatomyositis.J Am Acad Dermatol. 2016;74(2):377-379.

3. Farhangian ME, Huang WW, Feldman SR. Adherence to Oral and Topical Medications in Cutaneous Lupus Erythematosus is not Well Characterized. Dermatol Ther (Heidelb). 2015;5(2):91-105.

4. Ganança L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME. The role of cytokines in the pathophysiology of suicidal behavior.

Psychoneuroendocrinology. 2016;63:296-310.

5. Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. 2011;36(12):2452-2459.

6. Ramirez K, Niraula A, Sheridan JF. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and

behavioral alterations.Brain Behav Immun. 2016;51:154-168.

OBSERVATION

Human Papillomavirus–Induced Atypical Pigmented

High-grade Dysplasia of the Scrotum

Human papillomaviruses (HPVs) of the alpha genus induce a wide spectrum of epithelial lesions ranging from benign warts to anogenital dysplasia or invasive cancer. Penile intraepithe-lial neoplasia is a potential penile cancer precursor, and 50% to 90% of cases are induced by high-risk HPV types such as HPV16.1_{We herein describe a patient with an unusual} HPV-induced pigmented high-grade dysplasia of the scrotum that does not fit into the established clinical classification of ano-genital HPV-associated lesions.

Report of a Case|A man in his 60s of Arabian descent pre-sented with a growing pigmented lesion of the scrotum of 5 Table. Lupus Remission According to the Presence of Psychiatric

Disorders and Psychotropic Medications

Characteristic

Adjusted OR

(95% CI)a _{P Value}

Psychiatric disorder 0.47 (0.19-1.12) .09

Psychotropic medication 2.29 (0.94-5.59) .07

a_{Adjusted odds ratios (ORs) and 95% CIs were determined using a multivariate}

logistic regression. Letters

1332 JAMA Dermatology December 2017 Volume 153, Number 12 (Reprinted) jamadermatology.com