Psoriasis Case 5: Recalcitrant psoriasis and multiple comorbidities

A 37-year-old obese woman presents with widespread plaque psoriasis for more than 20 years for which a wide variety of therapies have been used. In addition to topical steroids and vitamin D analogs, she had received more than 300 PUVA treatments and 2 years of NB-UVB with her last phototherapy treatment being 3 years previously. The NB-UVB was not effective in adequately controlling her psoriasis. Medical history is significant for hypertension, dyslipidemia, and noninsulin-dependent diabetes mellitus, features consistent with the diagnosis of metabolic syndrome. She has had one basal cell carcinoma and one SCC involving her trunk, excised 4 and 2 years ago, respectively. Her menstrual cycles are regular and she is sexually active but not considering pregnancy. She reports drinking one ounce of alcohol daily for the past 12 years. Her current medications include metformin, rosuvastatin, fenofibrate, olmesartan, and an oral contraceptive. She has mildly elevated liver enzymes thought to be caused by a combination of her obesity (steatohepatitis) and her alcohol intake. On examination, she has hundreds of PUVA lentigines and several actinic keratoses involving sun-exposed areas of her arms, hands, and face. Thick psoriatic plaques are found on her trunk, extremities, and scalp involving 35% of her BSA. There is no onychodystrophy and no signs or symptoms of PsA are present. 

Discussion

This is a complex patient with several important comorbidities that potentially reduce her therapeutic options. In addition, given her obesity, noninsulin-dependent diabetes mellitus, dyslipidemia, and extensive burden of inflammation, she is at increased risk for infection, myocardial infarction, and even potential early demise.111 Her lack of response to long-term treatment with both types of UV-based therapy along with the extent of her psoriasis and her skin cancer history render treatment with UV light a poor choice.

Acitretin, an oral retinoid, is problematic for several reasons. First and foremost, the patient is a female of childbearing potential. Because there are no safe levels for oral retinoids in the face of pregnancy, the FDA has placed a 3-year postdosing moratorium on pregnancy with acitretin. Therefore and in a practical sense, female patients of childbearing potential should never receive oral acitretin. Because systemic isotretinoin has a much shorter half-life than acitretin, its safe and relatively effective use in female psoriasis patients of childbearing potential has been reported.112 There are additional concerns with acitretin therapy in this patient. For example, up to 16% of acitretin-treated patients will develop elevations in their serum transaminase levels and between 25% and 50% develop elevations in their serum triglycerides.53 These issues are additional important relative contraindications to the use of acitretin as a treatment for this patient’s psoriasis. Another consideration is the efficacy of acitretin. When used as monotherapy, it is the expert opinion of the authors that acitretin may need to be given in doses exceeding 25 mg/d to obtain significant improvement while recognizing that acitretin-induced mucocutaneous side effects, elevations of liver enzymes, and lipids are dose dependant. Although acitretin combined with phototherapy leads to a better response than monotherapy, this patient’s extensive phototherapy and skin cancer history make this combination approach far less attractive.

Cyclosporine, a highly effective oral medication, is another therapeutic option. Because of its nephrotoxicity, cyclosporine is traditionally used as a “rescue” medication in psoriasis and rarely used as a maintenance therapy, being approved in the United States for only up to 1 year of continuous therapy at a time.113 In addition to nephrotoxicity, cyclosporine has other potential systemic side effects that are relevant to this patient. Her history of hypertension, dyslipidemia, and mild elevations in liver enzymes must be considered before initiating treatment.53 In this patient, cyclosporine has a high probability of exacerbating her known hypertension. Her extensive UVB and PUVA treatment and skin cancer history increase significantly her likelihood of developing eruptive SCC and basal cell carcinoma should cyclosporine be added to her regimen.114 Cyclosporine is metabolized by the cytochrome P450 3A4 system and therefore the potential for drug interactions must be considered. This patient is being treated with rosuvastatin for her dyslipidemia and this presents risk of increased cyclosporine serum levels in this patient. Although these are all relative and not absolute contraindications to treatment with cyclosporine, the knowledge that cyclosporine is best used only as a rescue medication and not as a long-term therapy makes cyclosporine an unattractive option for this patient.

Navigate section 6 of the psoriasis guideline: Case-based review

Citation note

Menter A, Korman NJ, Elmets CA,Feldman SR, Gelfand JM, Gordon KB, Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011 Jul;65(1):137-74. 



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