Atypical Antipsychotics and Seborrheic Dermatitis: Three Case Reports

• Abstract
• Introduction
• Case Reports
• Patient No. 1, History
• Patient No. 2, History
• Patient No. 3, History
• Treatment
• Discussion
• Dermatological side effects of atypical anti-psychotics
• Conclusion
• Acknowledgements
• References

Abstract

Seborrheic dermatitis (SD) has no diagnostic criteria and its etiology remains unknown. SD is distributed in the areas rich in sebaceous glands. Initially, Malassezia furfur was thought to be the causing agent. Currently, SD is thought as not being proportional to the mean yeast count, but rather as an abnormal host immune response to the yeasts on the skin. There are a variety of topical and systemic antifungal agents available as a remedy. Corticosteroids and ultraviolet B are also used as treatment.

Introduction

Pre-marketing studies of several atypical antipsychotics showed an increased incidence of dermatological side effects compared to placebo (0% for placebo, 1% for risperidone and 2% for olanzapine, and ziprasidone (see [Table 2]). The studies have described rash, sweating, dry skin and seborrhea as side effects of antipsychotics, but none of the studies have included SD as a side effect of these medications. In the literature, SD has been described in relation to the development of parkinsonism in patients on antipsychotics, tardive dyskinesia and some psychiatric disorders. To our knowledge, there are no published reports of the atypical antipsychotics causing SD without the manifestations of parkinsonism or tardive dyskinesia. This article describes two patients with schizophrenia and one with schizoaffective disorder. These patients developed SD 3-4 weeks after starting olanzapine and risperidone and during the cross-over titration of ziprasidone and risperidone.

Case Reports

Patient No. 1, History

Mr. A was a 27-year-old Palestinian male, who was unemployed and homeless. He had a history of schizophrenia, paranoid type since age 18 with multiple psychiatric admissions and a history of non-adherence with prescribed medications and follow-up. He described symptoms of command hallucinations and was convinced that his brother was plotting to kill him.

On initial mental status examination, he was found to be disheveled with dirty clothes, was poorly related, and exhibited some psychomotor retardation. He was dysphoric, with a blunted affect. He demonstrated tangential thought processes and had persecutory delusions. He was admitted to the psychiatric unit for stabilization.

His initial physical examination was insignificant, without dermatological or other pathologies. In the emergency room the patient was started on haloperidol 5 mg tab. po q12 hours and benztropine 1 mg tab. po bid. Mr. A later reported taking olanzapine in the past with good effect, so haloperidol was discontinued and olanzapine was started at 10 mg tab. po qhs, titrated up to 15 mg and to 20 mg per day in two weeks. He continued having poor activities of daily living, remained isolative on the unit and did not attend any of the unit activities. Olanzapine was titrated up to 30 mg po qhs. There was no tardive dyskinesia noted.

Three weeks after his admission and being on olanzapine, Mr. A was found to have dandruff and mild scaling in his scalp and eye brows which was followed by pale erythema and oily appearance on the face and in the nasolabial folds.

A dermatology consult yielded a diagnosis of SD. The dermatologist advised Mr. A to use coal tar shampoo for his scalp and fluocinolone acetonide ointment 0.01% for his face. The lesions on the scalp and his face responded well to the treatment prescribed within one week. After discharge from the hospital the patient relocated to another city to live with his brother.

Patient No. 2, History

Mr. B was a 20-year-old Caucasian male, unemployed and homeless with a history of schizophrenia paranoid type, poly-substance dependence, and multiple attempts to hurt himself. His history included three in-patient admissions, lasting 3-4 weeks. During these admissions, Mr. B. exhibited auditory hallucinations and had thoughts of hurting himself. On all of these occasions he became non-adherent with medications immediately on discharge.

He started to decompensate when he stopped taking his medications, evidenced by poor sleep and appetite and inadequate self-care. He was brought to the emergency room when a friend called the ambulance because he felt depressed and expressed non-specific self-destructive thoughts. He was found to be guarded and isolative with minimal interactions with peers. At times he was seen talking to himself aloud.

A physical examination revealed no physical abnormalities, including no dermatological abnormalities.

The patient was started on risperidone, 1 mg tab po q12 h for psychosis, titrated to 6 mg po daily in 2-3 weeks. In the third week of his hospitalization after 20 days of being on risperidone, he complained of mild pruiritis in his scalp. On examination he was found to have dryness and dandruff in his scalp and sharply demarcated erythematous plaques with yellowish-red skin, on the face, especially in the nasolabial regions and also in the axillae.

A dermatology consult yielded a diagnosis of SD. He was prescribed sulphur ointment 2%, fluocinolone acetonine, 0.01% for topical administration on the face and tar shampoo for scalp. His dermatitis improved in one week.

Patient No. 3, History

Mr. C was a 25-year-old Bengali graduate student, with a history of schizoaffective disorder, bipolar type. The patient had three in-patient admissions in the past, extending from 1-2 months and a history of partial adherence to prescribed medications. He was brought to the emergency room following an argument at home where he exhibited aggression and made threats toward his family.

Mr. C's initial mental status examination showed he was minimally related, and had some psychomotor retardation. He was mildly dysphoric with constricted affect, and exhibited thought insertion and delusions of reference. He later reported hearing the voices of two persons talking between themselves.

His initial general physical exam did not endorse any dermatological pathology.

On the unit he was continued on his outpatient regimen of ziprasidone 40 mg tab. po bid and aripiprazole 30 mg po daily. Aripiprazole was discontinued due to non-response but ziprasidone titrated up to 80 mg po bid. Later, he was started on risperdone 1 mg tab. po q12 h due to partial response to psychosis. Within the next 3-4 weeks, ziprasidone was discontinued and risperidone titrated, up to 6 mg per day and subsequently to 8 mg per day.

One month after being on risperidone alone, the patient developed moderate to severe dandruff and dry scaling macules on his scalp with minimal involvement of the face. The patient reported similar complaints and involvement of his head and face in the past while on neuroleptics.

Mr. C was seen by a dermatologist, and was diagnosed with SD. The patient was recommended to have 2% sulphur, 2% salicylic acid, tar shampoo and benzyl peroxide 5% bid. His condition improved in the next 3-4 days.

Treatment

There are a variety of topical and systemic anti-fungal agents available for both therapeutic and prophylactic management, as shown in [Table 1].

Ketoconazole, miconazole, itraconazole and phototherapy are preferred agents for prophylaxis, although they can also be used in acute setting.

Phototherapy UVB, specifically UVB (311 nm TL-01) is effective in both acute treatment and prophylaxis [16].

Discussion

To date SD remains an ill defined and a poorly understood disorder. There are no standardized diagnostic criteria and much controversy exists regarding its etiology [12].

The term “seborrhea” refers to excess oil secretion [18]. The disorder is distributed in the areas that are rich in sebaceous glands such as the scalp, face, axillae and upper trunk.

The prevalence of SD is rated between 1% and 5% in the general population; it affects men slightly more than women [2]. In one study that focused on chronic wards of a large state hospital, 60% of patients with parkinsonian symptoms had SD [17], whereas 15% of patients without parkinsonian symptoms had SD [17].

Until recently, SD was thought to be caused by Malassezia furfur, a yeast, partly because SD was cured by antifungal agents. However, recent studies found the mean yeast counts in patients with SD were lower than those without the condition. As a result of these data and the pro-inflammatory properties of the yeast, it was suggested that SD is caused by an abnormal host immune response to yeasts on the skin [9].

Three other hypotheses considering the etiology of SD are based on the observation that patients with AIDS have a higher incidence of SD than the general population. The first hypothesis is that a normal number of Malassezia yeasts can trigger an inflammatory response after the stratum corneum cells interact with the immune system [1]. Second, SD in these patients might have been caused by immune hypersensitivity to Pityrosporum ovale [6]. Finally, the Pityrosporum genus may exacerbate SD in a manner similar to the involvement of Staphylococcus aureus in atopic dermatitis [19].

It has been hypothesized that hyperproliferation is a causal theory for SD. The treatments for SD, including anti-inflammatory and keratolytic medications such as corticosteroids and salicylic acids, have been used as evidence in support of this hypothesis [9].

Diseases of the central nervous system, particularly Parkinson disease, are clearly associated with an increased incidence (59.5%) and severity of SD, which could be a part of the neural-induced inflammation of the skin [16]. SD has been reported to be remarkably common in patients with spinal injury who live in obligatory recumbency [20].

Another hypothesis is aimed at explaining the propensity to SD of the subjects with Parkinson disease and other neurological conditions. It suggests reduced/abolished mobility leading to the pooling of the sebum rather to an absolute increase in sebum production [4].

Atypical antipsychotics have been known to cause multiple cutaneous side effects, as shown in [Table 2]. The rash mentioned in the introduction has been described as bullous eruption and furunculosis in rare instances in cases of risperidone and maculopapular, vesiculobullous and pustular rash in the case of olanzapine and ziprasidone. Risperidone olanzapine and ziprasidone did not cause SD in pre-marketing trials, nor have they been reported to cause SD.

SD has been reported to be associated with schizophrenia in 14% of the cases, 36% in mood disorders (major depression and bipolar disorder) and 25% in anxiety disorders [15]. SD has never been described in the literature as a manifestation of schizophrenia itself.

In the cases presented here, SD was observed in the absence of parkinsonian symptoms. This fact was partly based on zero score on Hoehn and Yahr staging of Parkinson's disease, unified Parkinson's disease rating scale (UPDRS), in the assessment of parkinsonian symptoms.

Dermatological side effects of atypical anti-psychotics

Dermatological side effects in pre-marketing trials on risperidone, olanzapine and ziprasidone, described in the literature are listed in [Table 2].

Conclusion

The cases described above are of patients without general medical problems or induced Parkinson's symptoms whose SD arose 3-4 weeks after the initiation of pharmacotherapy. These cases support the strength of the association between SD and pharmacotherapy. Resolution of the dermatitis after medication treatment, despite continuing olanzapine and risperidone, makes it difficult to be certain about the causal nature of this relation.

SD has been reported to occur at increasing frequency in patients with certain neurological disorders, especially Parkinson disease, at 59.5%. The association of SD has been even more robust with mood disorders, specifically with bipolar disorder. The prevalence of SD has also been found to be greater in patients suffering from AIDS [4] [8]. The patients described here did not have parkinsonism, bipolar disorder, major depression, or AIDS.

Only a small percentage of adverse cutaneous reactions are life-threatening, but these events might impact the patient's adherence to the medication intake. Nevertheless, physicians should be sensitive to the possibility of SD as a complication of olanzapine, risperidone, and possibly ziprasidone therapy. The most important step in decreasing early morbidity is early recognition of severe drug reactions.

Given that increased incidence of SD may be related to Parkinson disease, it is plausible that the increased incidence of SD in patients treated with antipsychotic agents may likewise be related to antipsychotic-induced parkinsonism. This likelihood should be further investigated.

Acknowledgements

The authors would like to thank Shazia Javaid, M.D. for her unrelenting support and encouragement.

References

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• 14 Pirkhammer D, Seeber A, Honigsmann , Ta-new A. Narrow-band ultraviolet B (TL-01) phototherapy is an effective and safe treatment option for patients with severe seborrheic dermatitis.  Br J Dermatol. 2000;  143 964-968
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Correspondence

J. RashidMD 

75 Avenue U

# 1R Brooklyn

New York 11223

USA

Phone: +1/718/946 93 29

Email: javaid.rashid@mssm.edu

References

• 1 Bergbrant IM, Faegemann J. Seborrheic dermatitis and Pityrosporum ovale; A cultural and immunological study.  Acta Derm Venereol. 1989;  69 332-335
  PubMedSearch in Google Scholar
• 2 Bonnetblanc JM, Bernard P. Benzoyl peroxide in seborrheic dermatitis.  Arch Dermatol. 1986;  122 752
  CrossrefPubMedSearch in Google Scholar
• 3 Caputo R, Barbareshi M. Itraconazole: New horizons.  G Ital Dermatol Venereol. 2002;  137 1-7
  PubMedSearch in Google Scholar
• 4 Cowley NC, Farr PM, Shuster S. The permissive effect of sebum in seborrheic dermatitis: an explanation of the rash in neurological disorders.  Br J Dermatol. 1990;  122 71-76
  PubMedSearch in Google Scholar
• 5 Cunha PR. Pimecrolimus cream 1% is effective in seborrhoeic dermatitis refractory to treatment with topical corticosteroids.  Acta Dermato-Venereologica. 2006;  86 69-70
  PubMedSearch in Google Scholar
• 6 Faergemann J. Management of seborrheic dermatitis and pityriasis versicolor.  Am J Clin Dermatol. 2000;  1 75-80
  CrossrefPubMedSearch in Google Scholar
• 7 Faeremann J. Seborrheic dermatitis and Pityrosporum orbiculare: Treatment of seborrheic dermatitis of the scalp with miconazole-hydrocortisone (Daktacort), miconazole and hydrocortisone.  Br J Dermatol. 1986;  114 695-700
  CrossrefPubMedSearch in Google Scholar
• 8 Faergemann J, Jones JC, Hettler O, Loria Y. Pityrosporum ovale (Malassezia furfur) as the causative agent of seborrheic dermatitis: New treatment options.  Br J Dermatol. 1996;  134 ((Suppl 46)) 12-15
  PubMedSearch in Google Scholar
• 9 Gupta AK, Madzia SE, Barta R. Etiology and management of seborrheic dermatitis.  Dermatology. 2004;  208 89-93
  CrossrefPubMedSearch in Google Scholar
• 10 Gupta AK, Nicol KA. Ciclopirox 1% shampoo for treatment of seborrheic Dermatitis.  Int J Dermatol. 2006;  45 66-69
  CrossrefPubMedSearch in Google Scholar
• 11 Lin AN. Sulphur revisited.  J Am Acad Dermatol. 1988;  18 553-558
  CrossrefPubMedSearch in Google Scholar
• 12 Mastrolonardo M, Diaferio A, Logroscino G. Seborrheic dermatitis, increased sebum excretion, and Parkinson's disease: a survey of impossible links.  Medical Hypothesis. 2003;  60 907-911
  CrossrefPubMedSearch in Google Scholar
• 13 Pierard-Franchimont C, Pierard GE. A double blind placebo-controlled study of ketokonazole and desonide gel combination in the treatment of facial seborrheic dermatitis.  Dermatology. 2002;  204 344-347
  CrossrefPubMedSearch in Google Scholar
• 14 Pirkhammer D, Seeber A, Honigsmann , Ta-new A. Narrow-band ultraviolet B (TL-01) phototherapy is an effective and safe treatment option for patients with severe seborrheic dermatitis.  Br J Dermatol. 2000;  143 964-968
  CrossrefPubMedSearch in Google Scholar
• 15 Rebora A. Patients with mood depression have a high prevalence of seborrhoeic dermatitis.  Acta Derm Venereol. 1990;  70 432-434
  PubMedSearch in Google Scholar
• 16 Binder RL, Jonelis FJ. Seborrheic dermatitis: A newly reported side effect of neuroleptics.  J Clin Psychiat. 1984;  45
  PubMedSearch in Google Scholar
• 17 Schwartz RA, Janusz CA, Janniger CK. Seborrheic dermatitis: An overview.  Am Fam Physician. 2006;  741 125-130
  PubMedSearch in Google Scholar
• 18 Shaw CJ.. , Overview of dermatitis, Up-To-Date 2005.http:// www.utdol.com/application/topic
  PubMed
• 19 Webster G. Seborrheic dermatitis.  Int. J. Dermatol. 1991;  30 843-844
  PubMedSearch in Google Scholar
• 20 Wilson CL, Walshe M. Incidence of seborrheic dermatitis in spinal injury patients.  Br J Dermatol. 1988;  33 ((Suppl)) 48
  PubMedSearch in Google Scholar

Correspondence

J. RashidMD 

75 Avenue U

# 1R Brooklyn

New York 11223

USA

Phone: +1/718/946 93 29

Email: javaid.rashid@mssm.edu