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Pearls in Dermatology: 2017

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Pearls in Dermatology: 2017

The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:

  • Nail psoriasis and psoriasis on the hands and feet
  • Genital wart treatment
  • Isotretinoin for acne
  • Cosmeceuticals for rosacea
  • Surgical technique with the flexible scalpel blade

Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.

Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.

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The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:

  • Nail psoriasis and psoriasis on the hands and feet
  • Genital wart treatment
  • Isotretinoin for acne
  • Cosmeceuticals for rosacea
  • Surgical technique with the flexible scalpel blade

Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.

Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.

The Pearls in Dermatology collection consists of our popular pearls from the year in one convenient file. Topics include:

  • Nail psoriasis and psoriasis on the hands and feet
  • Genital wart treatment
  • Isotretinoin for acne
  • Cosmeceuticals for rosacea
  • Surgical technique with the flexible scalpel blade

Editor’s Commentary provided by Vincent A. DeLeo, MD, Editor-in-Chief, Cutis.

Save this collection, print it, and/or share it with your colleagues. We hope this comprehensive collection will positively impact how you manage patients.

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Mood changes reported in cases of methotrexate use for dermatologic disease

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Mood changes are a rare side effect of methotrexate therapy, but ask about psychiatric side effects when using the drug, as when treating dermatologic disease, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.

Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.

KatarzynaBialasiewicz/Thinkstock
A 16-year-old girl with generalized lichen sclerosus and no prior psychiatric history began weekly oral methotrexate 10 mg (0.18 mg/kg) with folic acid supplementation 6 days per week after failing topical treatment and narrow-band ultraviolet B therapy. After her first two doses, she and her mother noted that she was feeling negative, had depressed mood, and was “mouthing off” to her parents. After 13 days, methotrexate was stopped, and her psychiatric symptoms went away within 2 weeks.

An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.

It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.

Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406).

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Mood changes are a rare side effect of methotrexate therapy, but ask about psychiatric side effects when using the drug, as when treating dermatologic disease, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.

Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.

KatarzynaBialasiewicz/Thinkstock
A 16-year-old girl with generalized lichen sclerosus and no prior psychiatric history began weekly oral methotrexate 10 mg (0.18 mg/kg) with folic acid supplementation 6 days per week after failing topical treatment and narrow-band ultraviolet B therapy. After her first two doses, she and her mother noted that she was feeling negative, had depressed mood, and was “mouthing off” to her parents. After 13 days, methotrexate was stopped, and her psychiatric symptoms went away within 2 weeks.

An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.

It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.

Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406).

 

Mood changes are a rare side effect of methotrexate therapy, but ask about psychiatric side effects when using the drug, as when treating dermatologic disease, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.

Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.

KatarzynaBialasiewicz/Thinkstock
A 16-year-old girl with generalized lichen sclerosus and no prior psychiatric history began weekly oral methotrexate 10 mg (0.18 mg/kg) with folic acid supplementation 6 days per week after failing topical treatment and narrow-band ultraviolet B therapy. After her first two doses, she and her mother noted that she was feeling negative, had depressed mood, and was “mouthing off” to her parents. After 13 days, methotrexate was stopped, and her psychiatric symptoms went away within 2 weeks.

An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.

It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.

Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406).

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Prior biologic exposure doesn’t diminish ixekizumab’s efficacy

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REPORTING FROM THE EADV CONGRESS

– Psoriasis patients switched to ixekizumab after previous exposure to another interleukin-17 inhibitor respond as well as those who are IL-17 antagonist naive, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This finding is of importance in real-world clinical practice because it’s not at all uncommon for psoriasis patients on one biologic to have to switch to another because of insufficient efficacy, side effects, or a change in insurance coverage. Physicians would like to know what sort of responses can be expected to whatever agent they prescribe next.

“We’ve seen many cases in which previous use of biologics may detrimentally impact the efficacy of subsequent biologic treatments. It’s a general rule of thumb that patients tend not to respond as well,” noted Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

However, that was not a problem in this secondary analysis of a large clinical trial whose primary purpose was to evaluate the relative safety and efficacy of ixekizumab (Taltz) when dosed every 2 weeks versus every 4 weeks.

“I think what we have seen here is a very compelling story: Previous exposure to biologics – and specifically to IL-17 antagonists – does not impact efficacy when you treat with ixekizumab, nor for that matter does it appear to impact safety,” the dermatologist said.

He reported on 1,227 patients with moderate to severe plaque psoriasis who were randomized to ixekizumab at 80 mg every 2 or 4 weeks following an initial 160 mg loading dose. Among those who started out on ixekizumab every 4 weeks, 306 patients got a per-protocol dose adjustment to biweekly therapy because of an insufficient response to monthly dosing as defined by a Physician’s Global Assessment score of 2 or more on two consecutive office visits during study weeks 12-40.

A total of 939 patients were IL-17 inhibitor naive. The other 288 had previously been on the IL-17 antagonists brodalumab (Siliq) or secukinumab (Cosentyx). The two groups had similar baseline demographics with the exception that the experienced cohort had on average a 22.2-year duration of psoriasis, 3.7 years more than IL-17 antagonist-naive patients.

In an intent-to-treat analysis, Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responses at week 52 didn’t differ significantly between the IL-17 inhibitor-naive and -experienced groups. In fact, patients with prior exposure to other IL-17 antagonists showed a consistent trend for slightly higher response rates (see graphic).

It was clear from this analysis that dosing ixekizumab every 2 weeks provides significantly better efficacy than was dosing every 4 weeks, Dr. Papp noted. Yet the approved dosing is 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

No new safety issues arose in this study. The only difference between the naive and experienced groups was a lower rate of allergic reactions/hypersensitivity in the experienced group. For example, in patients on ixekizumab every 2 weeks for the entire 52-week study period the incidence of such reactions was 11.5% in the IL-17 antagonist-naive group, compared with 4.1% in the experienced cohort. This isn’t really surprising, according to Dr. Papp.

“Most injection site reactions occur in the newbies,” he said.

The study was sponsored by Eli Lilly. Dr. Papp serves as a consultant and/or adviser to Lilly and numerous other pharmaceutical companies involved in the development of dermatologic therapies.
 

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REPORTING FROM THE EADV CONGRESS

– Psoriasis patients switched to ixekizumab after previous exposure to another interleukin-17 inhibitor respond as well as those who are IL-17 antagonist naive, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This finding is of importance in real-world clinical practice because it’s not at all uncommon for psoriasis patients on one biologic to have to switch to another because of insufficient efficacy, side effects, or a change in insurance coverage. Physicians would like to know what sort of responses can be expected to whatever agent they prescribe next.

“We’ve seen many cases in which previous use of biologics may detrimentally impact the efficacy of subsequent biologic treatments. It’s a general rule of thumb that patients tend not to respond as well,” noted Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

However, that was not a problem in this secondary analysis of a large clinical trial whose primary purpose was to evaluate the relative safety and efficacy of ixekizumab (Taltz) when dosed every 2 weeks versus every 4 weeks.

“I think what we have seen here is a very compelling story: Previous exposure to biologics – and specifically to IL-17 antagonists – does not impact efficacy when you treat with ixekizumab, nor for that matter does it appear to impact safety,” the dermatologist said.

He reported on 1,227 patients with moderate to severe plaque psoriasis who were randomized to ixekizumab at 80 mg every 2 or 4 weeks following an initial 160 mg loading dose. Among those who started out on ixekizumab every 4 weeks, 306 patients got a per-protocol dose adjustment to biweekly therapy because of an insufficient response to monthly dosing as defined by a Physician’s Global Assessment score of 2 or more on two consecutive office visits during study weeks 12-40.

A total of 939 patients were IL-17 inhibitor naive. The other 288 had previously been on the IL-17 antagonists brodalumab (Siliq) or secukinumab (Cosentyx). The two groups had similar baseline demographics with the exception that the experienced cohort had on average a 22.2-year duration of psoriasis, 3.7 years more than IL-17 antagonist-naive patients.

In an intent-to-treat analysis, Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responses at week 52 didn’t differ significantly between the IL-17 inhibitor-naive and -experienced groups. In fact, patients with prior exposure to other IL-17 antagonists showed a consistent trend for slightly higher response rates (see graphic).

It was clear from this analysis that dosing ixekizumab every 2 weeks provides significantly better efficacy than was dosing every 4 weeks, Dr. Papp noted. Yet the approved dosing is 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

No new safety issues arose in this study. The only difference between the naive and experienced groups was a lower rate of allergic reactions/hypersensitivity in the experienced group. For example, in patients on ixekizumab every 2 weeks for the entire 52-week study period the incidence of such reactions was 11.5% in the IL-17 antagonist-naive group, compared with 4.1% in the experienced cohort. This isn’t really surprising, according to Dr. Papp.

“Most injection site reactions occur in the newbies,” he said.

The study was sponsored by Eli Lilly. Dr. Papp serves as a consultant and/or adviser to Lilly and numerous other pharmaceutical companies involved in the development of dermatologic therapies.
 

 

REPORTING FROM THE EADV CONGRESS

– Psoriasis patients switched to ixekizumab after previous exposure to another interleukin-17 inhibitor respond as well as those who are IL-17 antagonist naive, Kim A. Papp, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This finding is of importance in real-world clinical practice because it’s not at all uncommon for psoriasis patients on one biologic to have to switch to another because of insufficient efficacy, side effects, or a change in insurance coverage. Physicians would like to know what sort of responses can be expected to whatever agent they prescribe next.

“We’ve seen many cases in which previous use of biologics may detrimentally impact the efficacy of subsequent biologic treatments. It’s a general rule of thumb that patients tend not to respond as well,” noted Dr. Papp, president of Probity Medical Research in Waterloo, Ont.

However, that was not a problem in this secondary analysis of a large clinical trial whose primary purpose was to evaluate the relative safety and efficacy of ixekizumab (Taltz) when dosed every 2 weeks versus every 4 weeks.

“I think what we have seen here is a very compelling story: Previous exposure to biologics – and specifically to IL-17 antagonists – does not impact efficacy when you treat with ixekizumab, nor for that matter does it appear to impact safety,” the dermatologist said.

He reported on 1,227 patients with moderate to severe plaque psoriasis who were randomized to ixekizumab at 80 mg every 2 or 4 weeks following an initial 160 mg loading dose. Among those who started out on ixekizumab every 4 weeks, 306 patients got a per-protocol dose adjustment to biweekly therapy because of an insufficient response to monthly dosing as defined by a Physician’s Global Assessment score of 2 or more on two consecutive office visits during study weeks 12-40.

A total of 939 patients were IL-17 inhibitor naive. The other 288 had previously been on the IL-17 antagonists brodalumab (Siliq) or secukinumab (Cosentyx). The two groups had similar baseline demographics with the exception that the experienced cohort had on average a 22.2-year duration of psoriasis, 3.7 years more than IL-17 antagonist-naive patients.

In an intent-to-treat analysis, Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responses at week 52 didn’t differ significantly between the IL-17 inhibitor-naive and -experienced groups. In fact, patients with prior exposure to other IL-17 antagonists showed a consistent trend for slightly higher response rates (see graphic).

It was clear from this analysis that dosing ixekizumab every 2 weeks provides significantly better efficacy than was dosing every 4 weeks, Dr. Papp noted. Yet the approved dosing is 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

No new safety issues arose in this study. The only difference between the naive and experienced groups was a lower rate of allergic reactions/hypersensitivity in the experienced group. For example, in patients on ixekizumab every 2 weeks for the entire 52-week study period the incidence of such reactions was 11.5% in the IL-17 antagonist-naive group, compared with 4.1% in the experienced cohort. This isn’t really surprising, according to Dr. Papp.

“Most injection site reactions occur in the newbies,” he said.

The study was sponsored by Eli Lilly. Dr. Papp serves as a consultant and/or adviser to Lilly and numerous other pharmaceutical companies involved in the development of dermatologic therapies.
 

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Scaly Pink Patches: Differentiating Psoriasis From Basal Cell Carcinoma

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Scaly Pink Patches: Differentiating Psoriasis From Basal Cell Carcinoma

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.3 To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Figure 1. Scaly pink papules of psoriasis (black arrows), and a new scaly red-pink patch of basal cell carcinoma (blue arrow).

Figure 2. Shiny white lines of basal cell carcinoma (blue arrows)(A and B) and branching vessel (black arrow)(B) of basal cell carcinoma.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al6 provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.4,5 Pan et al5 reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.5 Similarly, Lallas et al6 demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”4 Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.7-12

Figure 3. Dermoscopy of plaque psoriasis showing light red–pink background, red dots, and white scale.

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.15 Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.15 The positive predictive value of dermoscopy in BCC is as high as 97%.16 Additionally, multiple studies report a sensitivity of 95% to 99%5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,5 the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.17

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.15

References
  1. Kittler H, Pehamberger H, Wolff K, et al. Diagnostic accuracy of dermoscopy. Lancet Oncol. 2002;3:159-165.
  2. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159:669-676.
  3. Lallas A, Giacomel J, Argenziano G, et al. Dermoscopy in general dermatology: practical tips for the clinician. Br J Dermatol. 2014;170:514-526.
  4. Lallas A, Kyrgidis A, Tzellos TG, et al. Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br J Dermatol. 2012;166:1198-1205.
  5. Pan Y, Chamberlain AJ, Bailey M, et al. Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaque–features distinguishing superficial basal cell carcinoma, intraepidermal carcinoma, and psoriasis. J Am Acad Dermatol. 2008;59:268-274.
  6. Lallas A, Apalla Z, Argenziano G, et al. Dermoscopic pattern of psoriatic lesions on specific body sites. Dermatology. 2014;228:250-254.
  7. Almeida MC, Romiti R, Doche I, et al. Psoriatic scarring alopecia. An Bras Dermatol. 2013;88:29-31.
  8. Zalaudek I, Argenziano G. Dermoscopy subpatterns of inflammatory skin disorders. Arch Dermatol. 2006;142:808.
  9. Miteva M, Tosti A. Hair and scalp dermatoscopy. J Am Acad Dermatol. 2012;67:1040-1048.
  10. Vázquez-López F, Zaballos P, Fueyo-Casado A, et al. A dermoscopy subpattern of plaque-type psoriasis: red globular rings. Arch Dermatol. 2007;143:1612.
  11. Lacarrubba F, Nasca MR, Micali G. Videodermatoscopy enhances diagnostic capability in psoriatic balanitis. J Am Acad Dermatol. 2009;61:1084-1086.
  12. Liebman TN, Wang SQ. Detection of early basal cell carcinoma with dermoscopy in a patient with psoriasis. Dermatol Online J. 2011;17:12.
  13. Menzies SW, Westerhoff K, Rabinovitz H, et al. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol. 2000;136:1012-1016.
  14. Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell carcinoma: morphologic variability of global and local features and accuracy of diagnosis. J Am Acad Dermatol. 2010;62:67-75.
  15. Marghoob AA, Malvehy J, Braun RP, eds. An Atlas of Dermoscopy. 2nd ed. Boca Raton, FL: CRC Press; 2012.
  16. Nelson SA, Scope A, Rishpon A, et al. Accuracy and confidence in the clinical diagnosis of basal cell cancer using dermoscopy and reflex confocal microscopy. Int J Dermatol. 2016;55:1351-1356.
  17. Zalaudek I, Kreusch J, Giacomel J, et al. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. melanocytic skin tumors. J Am Acad Dermatol. 2010;63:361-374.
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Author and Disclosure Information

Ms. Hanna is from the Penn State College of Medicine, Penn State Milton S. Hersey Medical Center, Hershey, Pennsylvania. Drs. Cook, Foulke, and Seiverling are from the Department of Dermatology, Penn State Milton S. Hershey Medical Center. Dr. Seiverling also is from the Department of Family and Community Medicine.

The authors report no conflict of interest.

Correspondence: Courtney Hanna, MPH, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Dr, Hershey, PA 17033 ([email protected]).

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Ms. Hanna is from the Penn State College of Medicine, Penn State Milton S. Hersey Medical Center, Hershey, Pennsylvania. Drs. Cook, Foulke, and Seiverling are from the Department of Dermatology, Penn State Milton S. Hershey Medical Center. Dr. Seiverling also is from the Department of Family and Community Medicine.

The authors report no conflict of interest.

Correspondence: Courtney Hanna, MPH, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Dr, Hershey, PA 17033 ([email protected]).

Author and Disclosure Information

Ms. Hanna is from the Penn State College of Medicine, Penn State Milton S. Hersey Medical Center, Hershey, Pennsylvania. Drs. Cook, Foulke, and Seiverling are from the Department of Dermatology, Penn State Milton S. Hershey Medical Center. Dr. Seiverling also is from the Department of Family and Community Medicine.

The authors report no conflict of interest.

Correspondence: Courtney Hanna, MPH, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Dr, Hershey, PA 17033 ([email protected]).

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Related Articles

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.3 To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Figure 1. Scaly pink papules of psoriasis (black arrows), and a new scaly red-pink patch of basal cell carcinoma (blue arrow).

Figure 2. Shiny white lines of basal cell carcinoma (blue arrows)(A and B) and branching vessel (black arrow)(B) of basal cell carcinoma.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al6 provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.4,5 Pan et al5 reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.5 Similarly, Lallas et al6 demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”4 Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.7-12

Figure 3. Dermoscopy of plaque psoriasis showing light red–pink background, red dots, and white scale.

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.15 Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.15 The positive predictive value of dermoscopy in BCC is as high as 97%.16 Additionally, multiple studies report a sensitivity of 95% to 99%5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,5 the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.17

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.15

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.3 To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Figure 1. Scaly pink papules of psoriasis (black arrows), and a new scaly red-pink patch of basal cell carcinoma (blue arrow).

Figure 2. Shiny white lines of basal cell carcinoma (blue arrows)(A and B) and branching vessel (black arrow)(B) of basal cell carcinoma.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al6 provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.4,5 Pan et al5 reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.5 Similarly, Lallas et al6 demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”4 Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.7-12

Figure 3. Dermoscopy of plaque psoriasis showing light red–pink background, red dots, and white scale.

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.15 Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.15 The positive predictive value of dermoscopy in BCC is as high as 97%.16 Additionally, multiple studies report a sensitivity of 95% to 99%5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,5 the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.17

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.15

References
  1. Kittler H, Pehamberger H, Wolff K, et al. Diagnostic accuracy of dermoscopy. Lancet Oncol. 2002;3:159-165.
  2. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159:669-676.
  3. Lallas A, Giacomel J, Argenziano G, et al. Dermoscopy in general dermatology: practical tips for the clinician. Br J Dermatol. 2014;170:514-526.
  4. Lallas A, Kyrgidis A, Tzellos TG, et al. Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br J Dermatol. 2012;166:1198-1205.
  5. Pan Y, Chamberlain AJ, Bailey M, et al. Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaque–features distinguishing superficial basal cell carcinoma, intraepidermal carcinoma, and psoriasis. J Am Acad Dermatol. 2008;59:268-274.
  6. Lallas A, Apalla Z, Argenziano G, et al. Dermoscopic pattern of psoriatic lesions on specific body sites. Dermatology. 2014;228:250-254.
  7. Almeida MC, Romiti R, Doche I, et al. Psoriatic scarring alopecia. An Bras Dermatol. 2013;88:29-31.
  8. Zalaudek I, Argenziano G. Dermoscopy subpatterns of inflammatory skin disorders. Arch Dermatol. 2006;142:808.
  9. Miteva M, Tosti A. Hair and scalp dermatoscopy. J Am Acad Dermatol. 2012;67:1040-1048.
  10. Vázquez-López F, Zaballos P, Fueyo-Casado A, et al. A dermoscopy subpattern of plaque-type psoriasis: red globular rings. Arch Dermatol. 2007;143:1612.
  11. Lacarrubba F, Nasca MR, Micali G. Videodermatoscopy enhances diagnostic capability in psoriatic balanitis. J Am Acad Dermatol. 2009;61:1084-1086.
  12. Liebman TN, Wang SQ. Detection of early basal cell carcinoma with dermoscopy in a patient with psoriasis. Dermatol Online J. 2011;17:12.
  13. Menzies SW, Westerhoff K, Rabinovitz H, et al. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol. 2000;136:1012-1016.
  14. Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell carcinoma: morphologic variability of global and local features and accuracy of diagnosis. J Am Acad Dermatol. 2010;62:67-75.
  15. Marghoob AA, Malvehy J, Braun RP, eds. An Atlas of Dermoscopy. 2nd ed. Boca Raton, FL: CRC Press; 2012.
  16. Nelson SA, Scope A, Rishpon A, et al. Accuracy and confidence in the clinical diagnosis of basal cell cancer using dermoscopy and reflex confocal microscopy. Int J Dermatol. 2016;55:1351-1356.
  17. Zalaudek I, Kreusch J, Giacomel J, et al. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. melanocytic skin tumors. J Am Acad Dermatol. 2010;63:361-374.
References
  1. Kittler H, Pehamberger H, Wolff K, et al. Diagnostic accuracy of dermoscopy. Lancet Oncol. 2002;3:159-165.
  2. Vestergaard ME, Macaskill P, Holt PE, et al. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159:669-676.
  3. Lallas A, Giacomel J, Argenziano G, et al. Dermoscopy in general dermatology: practical tips for the clinician. Br J Dermatol. 2014;170:514-526.
  4. Lallas A, Kyrgidis A, Tzellos TG, et al. Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. Br J Dermatol. 2012;166:1198-1205.
  5. Pan Y, Chamberlain AJ, Bailey M, et al. Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaque–features distinguishing superficial basal cell carcinoma, intraepidermal carcinoma, and psoriasis. J Am Acad Dermatol. 2008;59:268-274.
  6. Lallas A, Apalla Z, Argenziano G, et al. Dermoscopic pattern of psoriatic lesions on specific body sites. Dermatology. 2014;228:250-254.
  7. Almeida MC, Romiti R, Doche I, et al. Psoriatic scarring alopecia. An Bras Dermatol. 2013;88:29-31.
  8. Zalaudek I, Argenziano G. Dermoscopy subpatterns of inflammatory skin disorders. Arch Dermatol. 2006;142:808.
  9. Miteva M, Tosti A. Hair and scalp dermatoscopy. J Am Acad Dermatol. 2012;67:1040-1048.
  10. Vázquez-López F, Zaballos P, Fueyo-Casado A, et al. A dermoscopy subpattern of plaque-type psoriasis: red globular rings. Arch Dermatol. 2007;143:1612.
  11. Lacarrubba F, Nasca MR, Micali G. Videodermatoscopy enhances diagnostic capability in psoriatic balanitis. J Am Acad Dermatol. 2009;61:1084-1086.
  12. Liebman TN, Wang SQ. Detection of early basal cell carcinoma with dermoscopy in a patient with psoriasis. Dermatol Online J. 2011;17:12.
  13. Menzies SW, Westerhoff K, Rabinovitz H, et al. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol. 2000;136:1012-1016.
  14. Altamura D, Menzies SW, Argenziano G, et al. Dermatoscopy of basal cell carcinoma: morphologic variability of global and local features and accuracy of diagnosis. J Am Acad Dermatol. 2010;62:67-75.
  15. Marghoob AA, Malvehy J, Braun RP, eds. An Atlas of Dermoscopy. 2nd ed. Boca Raton, FL: CRC Press; 2012.
  16. Nelson SA, Scope A, Rishpon A, et al. Accuracy and confidence in the clinical diagnosis of basal cell cancer using dermoscopy and reflex confocal microscopy. Int J Dermatol. 2016;55:1351-1356.
  17. Zalaudek I, Kreusch J, Giacomel J, et al. How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. melanocytic skin tumors. J Am Acad Dermatol. 2010;63:361-374.
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  • Dermoscopy has been largely utilized for the evaluation of malignant lesions. It also is gaining traction in the evaluation of inflammatory dermatoses.
  • Early distinction between basal cell carcinoma and psoriasis is important for both treatment options and health care costs.
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Psoriasis Treatment in HIV-Positive Patients: A Systematic Review of Systemic Immunosuppressive Therapies

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Psoriasis Treatment in HIV-Positive Patients: A Systematic Review of Systemic Immunosuppressive Therapies

The prevalence of psoriasis among human immunodeficiency virus (HIV)–positive patients in the United States is reported to be approximately 1% to 3%, which is similar to the rates reported for the general population.1 Recalcitrant cases of psoriasis in patients with no history of the condition can be the initial manifestation of HIV infection. In patients with preexisting psoriasis, a flare of their disease can be seen following infection, and progression of HIV correlates with worsening psoriasis.2 Psoriatic arthropathy also affects 23% to 50% of HIV-positive patients with psoriasis worldwide, which may be higher than the general population,1 with more severe joint disease.

The management of psoriatic disease in the HIV-positive population is challenging. The current first-line recommendations for treatment include topical therapies, phototherapy, and highly active antiretroviral therapy (HAART), followed by oral retinoids as second-line agents.3 However, the clinical course of psoriasis in HIV-positive patients often is progressive and refractory2; therefore, these therapies often are inadequate to control both skin and joint manifestations. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge because HIV-positive patients are already immunocompromised.

There currently are many systemic immunosuppressive agents used for the treatment of psoriatic disease, including oral agents (eg, methotrexate, hydroxyurea, cyclosporine), as well as newer biologic medications, including tumor necrosis factor (TNF) α inhibitors etanercept, adalimumab, infliximab, golimumab, and certolizumab pegol. Golimumab and certolizumab pegol currently are indicated for psoriatic arthritis only. Other newer biologic therapies include ustekinumab, which inhibits IL-12 and IL-23, and secukinumab, which inhibits IL-17A. The purpose of this systematic review is to evaluate the most current literature to explore the efficacy and safety data as they pertain to systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive individuals.

Methods

To investigate the efficacy and safety of systemic immunosuppressive therapies for psoriatic disease in HIV-positive individuals, a PubMed search of articles indexed for MEDLINE (1985-2015) was conducted using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with each of the following systemic immunosuppressive agents: methotrexate, hydroxyurea, cyclosporine, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab, and secukinumab. Pediatric cases and articles that were not available in the English language were excluded.

For each case, patient demographic information (ie, age, sex), prior failed psoriasis treatments, and history of HAART were documented. The dosing regimen of the systemic agent was noted when different from the US Food and Drug administration–approved dosage for psoriasis or psoriatic arthritis. The duration of immunosuppressive therapy as well as pretreatment and posttreatment CD4 and viral counts (when available) were collected. The response to treatment and adverse effects were summarized.

Results

Our review of the literature yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients, including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab (Table). There were no reports of the use of hydroxyurea, golimumab, certolizumab pegol, or secukinumab to treat psoriatic disease in this patient population.

Methotrexate
Eight individual cases of methotrexate used to treat psoriasis and/or psoriatic arthritis in HIV-positive patients were reported.4-6 Duvic et al6 described 4 patients with psoriatic disease that was treated with methotrexate with varying efficacy. One patient developed toxic encephalopathy, which improved after discontinuation of methotrexate; however, he died 5 months later from pneumocystis pneumonia. In this early study, none of the 4 patients were on antiretroviral therapy for HIV.6

In the cases reported by Masson et al4 and Maurer et al,5 4 patients were treated with a single antiretroviral agent and received appropriate prophylaxis against opportunistic infections. In 1 case, methotrexate was given at a chemotherapeutic dose of 525 mg once weekly for Kaposi sarcoma.4 In 2 of 4 cases, the patients developed pneumocystis pneumonia.4,5

Cyclosporine
There were 2 case reports of successful treatment of psoriatic disease with cyclosporine in HIV-positive patients.7,8 Skin and joint manifestations improved rapidly without reports of infection for 27 and 8 years.8 Both patients were treated with one antiretroviral agent.7,8

Etanercept
There were 5 case reports of successful treatment of psoriatic disease with etanercept. In all 5 cases the patients were on HAART, and the CD4 count increased or remained stable and viral count became undetectable or remained stable following treatment.9-13 In 2 cases, the patient also had hepatitis C virus, which remained stable throughout the treatment period.9,12 The maximum duration of treatment was 6 years, with only 1 reported adverse event.13 In this case reported by Aboulafia et al,13 the patient experienced recurrent polymicrobial infections, including enterococcal cellulitis, cystitis, and bacteremia, as well as pseudomonas pneumonia and septic arthritis. Therapy was discontinued at 6 months. Four months after discontinuation of etanercept, the patient died from infectious causes.13

Adalimumab
There was 1 case of successful treatment of psoriatic disease with adalimumab in an HIV-positive patient. In this case, the patient was on HAART, and CD4 and viral counts improved substantially after 30 months of treatment.14

Infliximab
Six individual cases of successful treatment of psoriatic disease with infliximab were reported.15-17 In a report by Cepeda et al,15 HIV-positive patients with various rheumatologic diseases were chosen to receive etanercept followed by adalimumab and/or infliximab if clinical improvement was not observed on etanercept. In 3 patients with psoriasis and psoriatic arthritis, inadequate response was observed on etanercept. Two of these 3 patients received adalimumab with only partial response. All 3 were treated with infliximab in the end and showed excellent response. One of the patients experienced facial abscess responsive to antibiotics and was continued on infliximab therapy without further complications. In all 6 cases of infliximab therapy, the patients were on HAART, and CD4 and viral counts improved or remained stable.15

Ustekinumab
There were 3 case reports of successful treatment of psoriatic disease with ustekinumab in HIV-positive patients on HAART. CD4 and viral counts improved or remained stable.18-20

 

 

Comment

Currently, all of the systemic immunosuppressive therapies approved for psoriatic disease have a warning by the US Food and Drug Administration for increased risk of serious infection. Given such labels, these therapies are not routinely prescribed for HIV-positive patients who are already immunocompromised; however, many HIV-positive patients have severe psoriatic disease that cannot be adequately treated with first- and second-line therapies including topical agents, phototherapy, or oral retinoids.

Our comprehensive review yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab. Although data are limited to case reports and case series, some trends were observed.

Efficacy
In most of the cases reviewed, the patients had inadequate improvement of psoriatic disease with first- and second-line therapies, which included antiretrovirals alone, topical agents, phototherapy, and oral retinoids. Some cases reported poor response to methotrexate and cyclosporine.4-8 Biologic agents were effective in many such cases.

Safety
Overall, there were 11 cases in which the patient was not on adequate HAART while being treated with systemic immunosuppressive therapy for psoriatic disease.4-8,15 Of them, 3 were associated with serious infection while on methotrexate.5,6 There was only 1 report of serious infection13 of 14 cases in which the patient was on concomitant HAART. In this case, which reported polymicrobial infections and subsequent death of the patient, the infections continued after discontinuing etanercept; thus, the association is unclear. Interestingly, despite multiple infections, the CD4 and viral counts were stable throughout treatment with etanercept.13

From reviewing the 4 total cases5,6,13 of serious infection, HAART appears to be a valuable concomitant treatment during systemic immunosuppressive therapy for HIV-positive patients; however, it does not necessarily prevent serious infections from occurring, and thus the clinician’s diligence in monitoring for signs and symptoms of infection remains important.

CD4 and Viral Counts
Although reports of CD4 and viral counts were not available in earlier studies,4-8 there were 15 cases that reported consistent pretreatment and posttreatment CD4 and viral counts during treatment with etanercept, adalimumab, infliximab, and ustekinumab.9-20 In all cases, the CD4 count was stable or increased. Similarly, the viral count was stable or decreased. All patients, except 1 by Cepeda et al,15 were on concomitant HAART.9-14,16-20

Although data are limited, treatment of psoriatic disease with biologic agents when used in combination with HAART may have beneficial effects on CD4 and viral counts. Tumor necrosis factor has a role in HIV expression through the action of nuclear factor κβ.21 An increase in TNF levels is shown to be associated with increased viral count, decreased CD4 count, and increased symptoms of HIV progression, such as fever, fatigue, cachexia, and dementia.22 Although more studies are necessary, TNF-α inhibitors may have a positive effect on HIV while simultaneously treating psoriatic disease. Other cytokines (eg, IL-12, IL-23, IL-17) involved in the mechanism of action of other biologic agents (ustekinumab and secukinumab) have not been shown to be directly associated with HIV activity; however, studies have shown that IL-10 has a role in inhibiting HIV-1 replication and inhibits secretion of proinflammatory cytokines such as IL-12 and TNF-α.21 It may be speculated that the inhibition of IL-12 and TNF-α may create a positive feedback effect to increase IL-10, which in turn inhibits HIV replication.

Conclusion

Although there are limited data on the efficacy and safety of systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive patients, a review of 25 individual cases suggest that these treatments are not only required but also are sufficient to treat some of the most resistant cases. It is possible that with adequate concomitant HAART and monitoring for signs and symptoms of infection, the likelihood of serious infection may be low. Furthermore, biologic agents may have a positive effect over other systemic immunosuppressive agents, such as methotrexate and cyclosporine, in improving CD4 and viral counts when used in combination with HAART. Although randomized controlled trials are necessary, current biologic therapies such as etanercept, adalimumab, infliximab, and ustekinumab may be safe viable options as third-line treatment of severe psoriasis in the HIV-positive population.

References
  1. Mallon E, Bunker CB. HIV-associated psoriasis. AIDS Patient Care STDS. 2000;14:239-246.
  2. Montazeri A, Kanitakis J, Bazex J. Psoriasis and HIV infection. Int J Dermatol. 1996;35:475-479.
  3. Menon K, Van Vorhees AS, Bebo BF, et al; National Psoriasis Foundation. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-299.
  4. Masson C, Chennebault JM, Leclech C. Is HIV infection contraindication to the use of methotrexate in psoriatic arthritis? J Rheumatol. 1995;22:2191.
  5. Maurer TA, Zackheim HS, Tuffanelli L, et al. The use of methotrexate for treatment of psoriasis in patients with HIV infection. J Am Acad Dermatol. 1994;31:372-375.
  6. Duvic M, Johnson TM, Rapini RP, et al. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol. 1987;123:1622-1632.
  7. Tourne L, Durez P, Van Vooren JP, et al. Alleviation of HIV-associated psoriasis and psoriatic arthritis with cyclosporine. J Am Acad Dermatol. 1997;37:501-502.
  8. Allen BR. Use of cyclosporine for psoriasis in HIV-positive patient. Lancet. 1992;339:686.
  9. Di Lernia V, Zoboli G, Ficarelli E. Long-term management of HIV/hepatitis C virus associated psoriasis with etanercept. Indian J Dermatol Venereol Leprol. 2013;79:444.
  10. Lee ES, Heller MM, Kamangar F, et al. Long-term etanercept use for severe generalized psoriasis in an HIV-infected individual: a case study. J Drugs Dermatol. 2012;11:413-414.
  11. Mikhail M, Weinberg JM, Smith BL. Successful treatment with etanercept of von Zumbusch pustular psoriasis in a patient with human immunodeficiency virus. Arch Dermatol. 2008;144:453-456.
  12. Linardaki G, Katsarou O, Ioannidou P, et al. Effective etanercept treatment for psoriatic arthritis complicating concomitant human immunodeficiency virus and hepatitis C virus infection. J Rheumatol. 2007;34:1353-1355.
  13. Aboulafia DM, Bundow D, Wilske K, et al. Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis. Mayo Clin Proc. 2000;75:1093-1098.
  14. Lindsey SF, Weiss J, Lee ES, et al. Treatment of severe psoriasis and psoriatic arthritis with adalimumab in an HIV-positive patient. J Drugs Dermatol. 2014;13:869-871.
  15. Cepeda EJ, Williams FM, Ishimori ML, et al. The use of anti-tumor necrosis factor therapy in HIV-positive individuals with rheumatic disease. Ann Rheum Dis. 2008;67:710-712.
  16. Sellam J, Bouvard B, Masson C, et al. Use of infliximab to treat psoriatic arthritis in HIV-positive patients. Joint Bone Spine. 2007;74:197-200.
  17. Bartke U, Venten I, Kreuter A, et al. Human immunodeficiency virus-associated psoriasis and psoriatic arthritis treated with infliximab. Br J Dermatol. 2004;150:784-786.
  18. Saeki H, Ito T, Hayashi M, et al. Successful treatment of ustekinumab in a severe psoriasis patient with human immunodeficiency virus infection. J Eur Acad Dermatol Venereol. 2015;29:1653-1655.
  19. Wieder S, Routt E, Levitt J, et al. Treatment of refractory psoriasis with ustekinumab in an HIV-positive patient: a case presentation and review of the biologic literature. Psoriasis Forum. 2014;20:96-102.
  20. Paparizos V, Rallis E, Kirsten L, et al. Ustekinumab for the treatment of HIV psoriasis. J Dermatol Treat. 2012;23:398-399.
  21. Kedzierska K, Crowe SM, Turville S, et al. The influence of cytokines, chemokines, and their receptors on HIV-1 replication in monocytes and macrophages. Rev Med Virol. 2003;13:39-56.
  22. Emer JJ. Is there a potential role for anti-tumor necrosis factor therapy in patients with human immunodeficiency virus? J Clin Aesthet Dermatol. 2009;2:29-35.
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From the Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco.

Drs. Nakamura, Abrouk, Farahnik, and Zhu report no conflict of interest. Dr. Bhutani is a researcher for AbbVie Inc; Janssen Biotech, Inc; and Novartis.

Correspondence: Mio Nakamura, MD, Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco, 515 Spruce St, San Francisco, CA 94118 ([email protected]).

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Drs. Nakamura, Abrouk, Farahnik, and Zhu report no conflict of interest. Dr. Bhutani is a researcher for AbbVie Inc; Janssen Biotech, Inc; and Novartis.

Correspondence: Mio Nakamura, MD, Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco, 515 Spruce St, San Francisco, CA 94118 ([email protected]).

Author and Disclosure Information

From the Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco.

Drs. Nakamura, Abrouk, Farahnik, and Zhu report no conflict of interest. Dr. Bhutani is a researcher for AbbVie Inc; Janssen Biotech, Inc; and Novartis.

Correspondence: Mio Nakamura, MD, Psoriasis and Skin Treatment Center, Department of Dermatology, University of California, San Francisco, 515 Spruce St, San Francisco, CA 94118 ([email protected]).

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Related Articles

The prevalence of psoriasis among human immunodeficiency virus (HIV)–positive patients in the United States is reported to be approximately 1% to 3%, which is similar to the rates reported for the general population.1 Recalcitrant cases of psoriasis in patients with no history of the condition can be the initial manifestation of HIV infection. In patients with preexisting psoriasis, a flare of their disease can be seen following infection, and progression of HIV correlates with worsening psoriasis.2 Psoriatic arthropathy also affects 23% to 50% of HIV-positive patients with psoriasis worldwide, which may be higher than the general population,1 with more severe joint disease.

The management of psoriatic disease in the HIV-positive population is challenging. The current first-line recommendations for treatment include topical therapies, phototherapy, and highly active antiretroviral therapy (HAART), followed by oral retinoids as second-line agents.3 However, the clinical course of psoriasis in HIV-positive patients often is progressive and refractory2; therefore, these therapies often are inadequate to control both skin and joint manifestations. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge because HIV-positive patients are already immunocompromised.

There currently are many systemic immunosuppressive agents used for the treatment of psoriatic disease, including oral agents (eg, methotrexate, hydroxyurea, cyclosporine), as well as newer biologic medications, including tumor necrosis factor (TNF) α inhibitors etanercept, adalimumab, infliximab, golimumab, and certolizumab pegol. Golimumab and certolizumab pegol currently are indicated for psoriatic arthritis only. Other newer biologic therapies include ustekinumab, which inhibits IL-12 and IL-23, and secukinumab, which inhibits IL-17A. The purpose of this systematic review is to evaluate the most current literature to explore the efficacy and safety data as they pertain to systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive individuals.

Methods

To investigate the efficacy and safety of systemic immunosuppressive therapies for psoriatic disease in HIV-positive individuals, a PubMed search of articles indexed for MEDLINE (1985-2015) was conducted using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with each of the following systemic immunosuppressive agents: methotrexate, hydroxyurea, cyclosporine, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab, and secukinumab. Pediatric cases and articles that were not available in the English language were excluded.

For each case, patient demographic information (ie, age, sex), prior failed psoriasis treatments, and history of HAART were documented. The dosing regimen of the systemic agent was noted when different from the US Food and Drug administration–approved dosage for psoriasis or psoriatic arthritis. The duration of immunosuppressive therapy as well as pretreatment and posttreatment CD4 and viral counts (when available) were collected. The response to treatment and adverse effects were summarized.

Results

Our review of the literature yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients, including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab (Table). There were no reports of the use of hydroxyurea, golimumab, certolizumab pegol, or secukinumab to treat psoriatic disease in this patient population.

Methotrexate
Eight individual cases of methotrexate used to treat psoriasis and/or psoriatic arthritis in HIV-positive patients were reported.4-6 Duvic et al6 described 4 patients with psoriatic disease that was treated with methotrexate with varying efficacy. One patient developed toxic encephalopathy, which improved after discontinuation of methotrexate; however, he died 5 months later from pneumocystis pneumonia. In this early study, none of the 4 patients were on antiretroviral therapy for HIV.6

In the cases reported by Masson et al4 and Maurer et al,5 4 patients were treated with a single antiretroviral agent and received appropriate prophylaxis against opportunistic infections. In 1 case, methotrexate was given at a chemotherapeutic dose of 525 mg once weekly for Kaposi sarcoma.4 In 2 of 4 cases, the patients developed pneumocystis pneumonia.4,5

Cyclosporine
There were 2 case reports of successful treatment of psoriatic disease with cyclosporine in HIV-positive patients.7,8 Skin and joint manifestations improved rapidly without reports of infection for 27 and 8 years.8 Both patients were treated with one antiretroviral agent.7,8

Etanercept
There were 5 case reports of successful treatment of psoriatic disease with etanercept. In all 5 cases the patients were on HAART, and the CD4 count increased or remained stable and viral count became undetectable or remained stable following treatment.9-13 In 2 cases, the patient also had hepatitis C virus, which remained stable throughout the treatment period.9,12 The maximum duration of treatment was 6 years, with only 1 reported adverse event.13 In this case reported by Aboulafia et al,13 the patient experienced recurrent polymicrobial infections, including enterococcal cellulitis, cystitis, and bacteremia, as well as pseudomonas pneumonia and septic arthritis. Therapy was discontinued at 6 months. Four months after discontinuation of etanercept, the patient died from infectious causes.13

Adalimumab
There was 1 case of successful treatment of psoriatic disease with adalimumab in an HIV-positive patient. In this case, the patient was on HAART, and CD4 and viral counts improved substantially after 30 months of treatment.14

Infliximab
Six individual cases of successful treatment of psoriatic disease with infliximab were reported.15-17 In a report by Cepeda et al,15 HIV-positive patients with various rheumatologic diseases were chosen to receive etanercept followed by adalimumab and/or infliximab if clinical improvement was not observed on etanercept. In 3 patients with psoriasis and psoriatic arthritis, inadequate response was observed on etanercept. Two of these 3 patients received adalimumab with only partial response. All 3 were treated with infliximab in the end and showed excellent response. One of the patients experienced facial abscess responsive to antibiotics and was continued on infliximab therapy without further complications. In all 6 cases of infliximab therapy, the patients were on HAART, and CD4 and viral counts improved or remained stable.15

Ustekinumab
There were 3 case reports of successful treatment of psoriatic disease with ustekinumab in HIV-positive patients on HAART. CD4 and viral counts improved or remained stable.18-20

 

 

Comment

Currently, all of the systemic immunosuppressive therapies approved for psoriatic disease have a warning by the US Food and Drug Administration for increased risk of serious infection. Given such labels, these therapies are not routinely prescribed for HIV-positive patients who are already immunocompromised; however, many HIV-positive patients have severe psoriatic disease that cannot be adequately treated with first- and second-line therapies including topical agents, phototherapy, or oral retinoids.

Our comprehensive review yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab. Although data are limited to case reports and case series, some trends were observed.

Efficacy
In most of the cases reviewed, the patients had inadequate improvement of psoriatic disease with first- and second-line therapies, which included antiretrovirals alone, topical agents, phototherapy, and oral retinoids. Some cases reported poor response to methotrexate and cyclosporine.4-8 Biologic agents were effective in many such cases.

Safety
Overall, there were 11 cases in which the patient was not on adequate HAART while being treated with systemic immunosuppressive therapy for psoriatic disease.4-8,15 Of them, 3 were associated with serious infection while on methotrexate.5,6 There was only 1 report of serious infection13 of 14 cases in which the patient was on concomitant HAART. In this case, which reported polymicrobial infections and subsequent death of the patient, the infections continued after discontinuing etanercept; thus, the association is unclear. Interestingly, despite multiple infections, the CD4 and viral counts were stable throughout treatment with etanercept.13

From reviewing the 4 total cases5,6,13 of serious infection, HAART appears to be a valuable concomitant treatment during systemic immunosuppressive therapy for HIV-positive patients; however, it does not necessarily prevent serious infections from occurring, and thus the clinician’s diligence in monitoring for signs and symptoms of infection remains important.

CD4 and Viral Counts
Although reports of CD4 and viral counts were not available in earlier studies,4-8 there were 15 cases that reported consistent pretreatment and posttreatment CD4 and viral counts during treatment with etanercept, adalimumab, infliximab, and ustekinumab.9-20 In all cases, the CD4 count was stable or increased. Similarly, the viral count was stable or decreased. All patients, except 1 by Cepeda et al,15 were on concomitant HAART.9-14,16-20

Although data are limited, treatment of psoriatic disease with biologic agents when used in combination with HAART may have beneficial effects on CD4 and viral counts. Tumor necrosis factor has a role in HIV expression through the action of nuclear factor κβ.21 An increase in TNF levels is shown to be associated with increased viral count, decreased CD4 count, and increased symptoms of HIV progression, such as fever, fatigue, cachexia, and dementia.22 Although more studies are necessary, TNF-α inhibitors may have a positive effect on HIV while simultaneously treating psoriatic disease. Other cytokines (eg, IL-12, IL-23, IL-17) involved in the mechanism of action of other biologic agents (ustekinumab and secukinumab) have not been shown to be directly associated with HIV activity; however, studies have shown that IL-10 has a role in inhibiting HIV-1 replication and inhibits secretion of proinflammatory cytokines such as IL-12 and TNF-α.21 It may be speculated that the inhibition of IL-12 and TNF-α may create a positive feedback effect to increase IL-10, which in turn inhibits HIV replication.

Conclusion

Although there are limited data on the efficacy and safety of systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive patients, a review of 25 individual cases suggest that these treatments are not only required but also are sufficient to treat some of the most resistant cases. It is possible that with adequate concomitant HAART and monitoring for signs and symptoms of infection, the likelihood of serious infection may be low. Furthermore, biologic agents may have a positive effect over other systemic immunosuppressive agents, such as methotrexate and cyclosporine, in improving CD4 and viral counts when used in combination with HAART. Although randomized controlled trials are necessary, current biologic therapies such as etanercept, adalimumab, infliximab, and ustekinumab may be safe viable options as third-line treatment of severe psoriasis in the HIV-positive population.

The prevalence of psoriasis among human immunodeficiency virus (HIV)–positive patients in the United States is reported to be approximately 1% to 3%, which is similar to the rates reported for the general population.1 Recalcitrant cases of psoriasis in patients with no history of the condition can be the initial manifestation of HIV infection. In patients with preexisting psoriasis, a flare of their disease can be seen following infection, and progression of HIV correlates with worsening psoriasis.2 Psoriatic arthropathy also affects 23% to 50% of HIV-positive patients with psoriasis worldwide, which may be higher than the general population,1 with more severe joint disease.

The management of psoriatic disease in the HIV-positive population is challenging. The current first-line recommendations for treatment include topical therapies, phototherapy, and highly active antiretroviral therapy (HAART), followed by oral retinoids as second-line agents.3 However, the clinical course of psoriasis in HIV-positive patients often is progressive and refractory2; therefore, these therapies often are inadequate to control both skin and joint manifestations. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge because HIV-positive patients are already immunocompromised.

There currently are many systemic immunosuppressive agents used for the treatment of psoriatic disease, including oral agents (eg, methotrexate, hydroxyurea, cyclosporine), as well as newer biologic medications, including tumor necrosis factor (TNF) α inhibitors etanercept, adalimumab, infliximab, golimumab, and certolizumab pegol. Golimumab and certolizumab pegol currently are indicated for psoriatic arthritis only. Other newer biologic therapies include ustekinumab, which inhibits IL-12 and IL-23, and secukinumab, which inhibits IL-17A. The purpose of this systematic review is to evaluate the most current literature to explore the efficacy and safety data as they pertain to systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive individuals.

Methods

To investigate the efficacy and safety of systemic immunosuppressive therapies for psoriatic disease in HIV-positive individuals, a PubMed search of articles indexed for MEDLINE (1985-2015) was conducted using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with each of the following systemic immunosuppressive agents: methotrexate, hydroxyurea, cyclosporine, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab, and secukinumab. Pediatric cases and articles that were not available in the English language were excluded.

For each case, patient demographic information (ie, age, sex), prior failed psoriasis treatments, and history of HAART were documented. The dosing regimen of the systemic agent was noted when different from the US Food and Drug administration–approved dosage for psoriasis or psoriatic arthritis. The duration of immunosuppressive therapy as well as pretreatment and posttreatment CD4 and viral counts (when available) were collected. The response to treatment and adverse effects were summarized.

Results

Our review of the literature yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients, including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab (Table). There were no reports of the use of hydroxyurea, golimumab, certolizumab pegol, or secukinumab to treat psoriatic disease in this patient population.

Methotrexate
Eight individual cases of methotrexate used to treat psoriasis and/or psoriatic arthritis in HIV-positive patients were reported.4-6 Duvic et al6 described 4 patients with psoriatic disease that was treated with methotrexate with varying efficacy. One patient developed toxic encephalopathy, which improved after discontinuation of methotrexate; however, he died 5 months later from pneumocystis pneumonia. In this early study, none of the 4 patients were on antiretroviral therapy for HIV.6

In the cases reported by Masson et al4 and Maurer et al,5 4 patients were treated with a single antiretroviral agent and received appropriate prophylaxis against opportunistic infections. In 1 case, methotrexate was given at a chemotherapeutic dose of 525 mg once weekly for Kaposi sarcoma.4 In 2 of 4 cases, the patients developed pneumocystis pneumonia.4,5

Cyclosporine
There were 2 case reports of successful treatment of psoriatic disease with cyclosporine in HIV-positive patients.7,8 Skin and joint manifestations improved rapidly without reports of infection for 27 and 8 years.8 Both patients were treated with one antiretroviral agent.7,8

Etanercept
There were 5 case reports of successful treatment of psoriatic disease with etanercept. In all 5 cases the patients were on HAART, and the CD4 count increased or remained stable and viral count became undetectable or remained stable following treatment.9-13 In 2 cases, the patient also had hepatitis C virus, which remained stable throughout the treatment period.9,12 The maximum duration of treatment was 6 years, with only 1 reported adverse event.13 In this case reported by Aboulafia et al,13 the patient experienced recurrent polymicrobial infections, including enterococcal cellulitis, cystitis, and bacteremia, as well as pseudomonas pneumonia and septic arthritis. Therapy was discontinued at 6 months. Four months after discontinuation of etanercept, the patient died from infectious causes.13

Adalimumab
There was 1 case of successful treatment of psoriatic disease with adalimumab in an HIV-positive patient. In this case, the patient was on HAART, and CD4 and viral counts improved substantially after 30 months of treatment.14

Infliximab
Six individual cases of successful treatment of psoriatic disease with infliximab were reported.15-17 In a report by Cepeda et al,15 HIV-positive patients with various rheumatologic diseases were chosen to receive etanercept followed by adalimumab and/or infliximab if clinical improvement was not observed on etanercept. In 3 patients with psoriasis and psoriatic arthritis, inadequate response was observed on etanercept. Two of these 3 patients received adalimumab with only partial response. All 3 were treated with infliximab in the end and showed excellent response. One of the patients experienced facial abscess responsive to antibiotics and was continued on infliximab therapy without further complications. In all 6 cases of infliximab therapy, the patients were on HAART, and CD4 and viral counts improved or remained stable.15

Ustekinumab
There were 3 case reports of successful treatment of psoriatic disease with ustekinumab in HIV-positive patients on HAART. CD4 and viral counts improved or remained stable.18-20

 

 

Comment

Currently, all of the systemic immunosuppressive therapies approved for psoriatic disease have a warning by the US Food and Drug Administration for increased risk of serious infection. Given such labels, these therapies are not routinely prescribed for HIV-positive patients who are already immunocompromised; however, many HIV-positive patients have severe psoriatic disease that cannot be adequately treated with first- and second-line therapies including topical agents, phototherapy, or oral retinoids.

Our comprehensive review yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab. Although data are limited to case reports and case series, some trends were observed.

Efficacy
In most of the cases reviewed, the patients had inadequate improvement of psoriatic disease with first- and second-line therapies, which included antiretrovirals alone, topical agents, phototherapy, and oral retinoids. Some cases reported poor response to methotrexate and cyclosporine.4-8 Biologic agents were effective in many such cases.

Safety
Overall, there were 11 cases in which the patient was not on adequate HAART while being treated with systemic immunosuppressive therapy for psoriatic disease.4-8,15 Of them, 3 were associated with serious infection while on methotrexate.5,6 There was only 1 report of serious infection13 of 14 cases in which the patient was on concomitant HAART. In this case, which reported polymicrobial infections and subsequent death of the patient, the infections continued after discontinuing etanercept; thus, the association is unclear. Interestingly, despite multiple infections, the CD4 and viral counts were stable throughout treatment with etanercept.13

From reviewing the 4 total cases5,6,13 of serious infection, HAART appears to be a valuable concomitant treatment during systemic immunosuppressive therapy for HIV-positive patients; however, it does not necessarily prevent serious infections from occurring, and thus the clinician’s diligence in monitoring for signs and symptoms of infection remains important.

CD4 and Viral Counts
Although reports of CD4 and viral counts were not available in earlier studies,4-8 there were 15 cases that reported consistent pretreatment and posttreatment CD4 and viral counts during treatment with etanercept, adalimumab, infliximab, and ustekinumab.9-20 In all cases, the CD4 count was stable or increased. Similarly, the viral count was stable or decreased. All patients, except 1 by Cepeda et al,15 were on concomitant HAART.9-14,16-20

Although data are limited, treatment of psoriatic disease with biologic agents when used in combination with HAART may have beneficial effects on CD4 and viral counts. Tumor necrosis factor has a role in HIV expression through the action of nuclear factor κβ.21 An increase in TNF levels is shown to be associated with increased viral count, decreased CD4 count, and increased symptoms of HIV progression, such as fever, fatigue, cachexia, and dementia.22 Although more studies are necessary, TNF-α inhibitors may have a positive effect on HIV while simultaneously treating psoriatic disease. Other cytokines (eg, IL-12, IL-23, IL-17) involved in the mechanism of action of other biologic agents (ustekinumab and secukinumab) have not been shown to be directly associated with HIV activity; however, studies have shown that IL-10 has a role in inhibiting HIV-1 replication and inhibits secretion of proinflammatory cytokines such as IL-12 and TNF-α.21 It may be speculated that the inhibition of IL-12 and TNF-α may create a positive feedback effect to increase IL-10, which in turn inhibits HIV replication.

Conclusion

Although there are limited data on the efficacy and safety of systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive patients, a review of 25 individual cases suggest that these treatments are not only required but also are sufficient to treat some of the most resistant cases. It is possible that with adequate concomitant HAART and monitoring for signs and symptoms of infection, the likelihood of serious infection may be low. Furthermore, biologic agents may have a positive effect over other systemic immunosuppressive agents, such as methotrexate and cyclosporine, in improving CD4 and viral counts when used in combination with HAART. Although randomized controlled trials are necessary, current biologic therapies such as etanercept, adalimumab, infliximab, and ustekinumab may be safe viable options as third-line treatment of severe psoriasis in the HIV-positive population.

References
  1. Mallon E, Bunker CB. HIV-associated psoriasis. AIDS Patient Care STDS. 2000;14:239-246.
  2. Montazeri A, Kanitakis J, Bazex J. Psoriasis and HIV infection. Int J Dermatol. 1996;35:475-479.
  3. Menon K, Van Vorhees AS, Bebo BF, et al; National Psoriasis Foundation. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-299.
  4. Masson C, Chennebault JM, Leclech C. Is HIV infection contraindication to the use of methotrexate in psoriatic arthritis? J Rheumatol. 1995;22:2191.
  5. Maurer TA, Zackheim HS, Tuffanelli L, et al. The use of methotrexate for treatment of psoriasis in patients with HIV infection. J Am Acad Dermatol. 1994;31:372-375.
  6. Duvic M, Johnson TM, Rapini RP, et al. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol. 1987;123:1622-1632.
  7. Tourne L, Durez P, Van Vooren JP, et al. Alleviation of HIV-associated psoriasis and psoriatic arthritis with cyclosporine. J Am Acad Dermatol. 1997;37:501-502.
  8. Allen BR. Use of cyclosporine for psoriasis in HIV-positive patient. Lancet. 1992;339:686.
  9. Di Lernia V, Zoboli G, Ficarelli E. Long-term management of HIV/hepatitis C virus associated psoriasis with etanercept. Indian J Dermatol Venereol Leprol. 2013;79:444.
  10. Lee ES, Heller MM, Kamangar F, et al. Long-term etanercept use for severe generalized psoriasis in an HIV-infected individual: a case study. J Drugs Dermatol. 2012;11:413-414.
  11. Mikhail M, Weinberg JM, Smith BL. Successful treatment with etanercept of von Zumbusch pustular psoriasis in a patient with human immunodeficiency virus. Arch Dermatol. 2008;144:453-456.
  12. Linardaki G, Katsarou O, Ioannidou P, et al. Effective etanercept treatment for psoriatic arthritis complicating concomitant human immunodeficiency virus and hepatitis C virus infection. J Rheumatol. 2007;34:1353-1355.
  13. Aboulafia DM, Bundow D, Wilske K, et al. Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis. Mayo Clin Proc. 2000;75:1093-1098.
  14. Lindsey SF, Weiss J, Lee ES, et al. Treatment of severe psoriasis and psoriatic arthritis with adalimumab in an HIV-positive patient. J Drugs Dermatol. 2014;13:869-871.
  15. Cepeda EJ, Williams FM, Ishimori ML, et al. The use of anti-tumor necrosis factor therapy in HIV-positive individuals with rheumatic disease. Ann Rheum Dis. 2008;67:710-712.
  16. Sellam J, Bouvard B, Masson C, et al. Use of infliximab to treat psoriatic arthritis in HIV-positive patients. Joint Bone Spine. 2007;74:197-200.
  17. Bartke U, Venten I, Kreuter A, et al. Human immunodeficiency virus-associated psoriasis and psoriatic arthritis treated with infliximab. Br J Dermatol. 2004;150:784-786.
  18. Saeki H, Ito T, Hayashi M, et al. Successful treatment of ustekinumab in a severe psoriasis patient with human immunodeficiency virus infection. J Eur Acad Dermatol Venereol. 2015;29:1653-1655.
  19. Wieder S, Routt E, Levitt J, et al. Treatment of refractory psoriasis with ustekinumab in an HIV-positive patient: a case presentation and review of the biologic literature. Psoriasis Forum. 2014;20:96-102.
  20. Paparizos V, Rallis E, Kirsten L, et al. Ustekinumab for the treatment of HIV psoriasis. J Dermatol Treat. 2012;23:398-399.
  21. Kedzierska K, Crowe SM, Turville S, et al. The influence of cytokines, chemokines, and their receptors on HIV-1 replication in monocytes and macrophages. Rev Med Virol. 2003;13:39-56.
  22. Emer JJ. Is there a potential role for anti-tumor necrosis factor therapy in patients with human immunodeficiency virus? J Clin Aesthet Dermatol. 2009;2:29-35.
References
  1. Mallon E, Bunker CB. HIV-associated psoriasis. AIDS Patient Care STDS. 2000;14:239-246.
  2. Montazeri A, Kanitakis J, Bazex J. Psoriasis and HIV infection. Int J Dermatol. 1996;35:475-479.
  3. Menon K, Van Vorhees AS, Bebo BF, et al; National Psoriasis Foundation. Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62:291-299.
  4. Masson C, Chennebault JM, Leclech C. Is HIV infection contraindication to the use of methotrexate in psoriatic arthritis? J Rheumatol. 1995;22:2191.
  5. Maurer TA, Zackheim HS, Tuffanelli L, et al. The use of methotrexate for treatment of psoriasis in patients with HIV infection. J Am Acad Dermatol. 1994;31:372-375.
  6. Duvic M, Johnson TM, Rapini RP, et al. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol. 1987;123:1622-1632.
  7. Tourne L, Durez P, Van Vooren JP, et al. Alleviation of HIV-associated psoriasis and psoriatic arthritis with cyclosporine. J Am Acad Dermatol. 1997;37:501-502.
  8. Allen BR. Use of cyclosporine for psoriasis in HIV-positive patient. Lancet. 1992;339:686.
  9. Di Lernia V, Zoboli G, Ficarelli E. Long-term management of HIV/hepatitis C virus associated psoriasis with etanercept. Indian J Dermatol Venereol Leprol. 2013;79:444.
  10. Lee ES, Heller MM, Kamangar F, et al. Long-term etanercept use for severe generalized psoriasis in an HIV-infected individual: a case study. J Drugs Dermatol. 2012;11:413-414.
  11. Mikhail M, Weinberg JM, Smith BL. Successful treatment with etanercept of von Zumbusch pustular psoriasis in a patient with human immunodeficiency virus. Arch Dermatol. 2008;144:453-456.
  12. Linardaki G, Katsarou O, Ioannidou P, et al. Effective etanercept treatment for psoriatic arthritis complicating concomitant human immunodeficiency virus and hepatitis C virus infection. J Rheumatol. 2007;34:1353-1355.
  13. Aboulafia DM, Bundow D, Wilske K, et al. Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis. Mayo Clin Proc. 2000;75:1093-1098.
  14. Lindsey SF, Weiss J, Lee ES, et al. Treatment of severe psoriasis and psoriatic arthritis with adalimumab in an HIV-positive patient. J Drugs Dermatol. 2014;13:869-871.
  15. Cepeda EJ, Williams FM, Ishimori ML, et al. The use of anti-tumor necrosis factor therapy in HIV-positive individuals with rheumatic disease. Ann Rheum Dis. 2008;67:710-712.
  16. Sellam J, Bouvard B, Masson C, et al. Use of infliximab to treat psoriatic arthritis in HIV-positive patients. Joint Bone Spine. 2007;74:197-200.
  17. Bartke U, Venten I, Kreuter A, et al. Human immunodeficiency virus-associated psoriasis and psoriatic arthritis treated with infliximab. Br J Dermatol. 2004;150:784-786.
  18. Saeki H, Ito T, Hayashi M, et al. Successful treatment of ustekinumab in a severe psoriasis patient with human immunodeficiency virus infection. J Eur Acad Dermatol Venereol. 2015;29:1653-1655.
  19. Wieder S, Routt E, Levitt J, et al. Treatment of refractory psoriasis with ustekinumab in an HIV-positive patient: a case presentation and review of the biologic literature. Psoriasis Forum. 2014;20:96-102.
  20. Paparizos V, Rallis E, Kirsten L, et al. Ustekinumab for the treatment of HIV psoriasis. J Dermatol Treat. 2012;23:398-399.
  21. Kedzierska K, Crowe SM, Turville S, et al. The influence of cytokines, chemokines, and their receptors on HIV-1 replication in monocytes and macrophages. Rev Med Virol. 2003;13:39-56.
  22. Emer JJ. Is there a potential role for anti-tumor necrosis factor therapy in patients with human immunodeficiency virus? J Clin Aesthet Dermatol. 2009;2:29-35.
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  • There are limited data on the use of systemic immunosuppressive therapies for the treatment of psoriatic disease in human immunodeficiency virus–positive patients.
  • The limited data suggest that biologic therapies may be effective for cases of psoriasis recalcitrant to other systemic agents and may have a positive effect on CD4 and viral counts when used in combination with highly active antiretroviral therapy.
  • Further research is needed.
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The Clock Is Ticking

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The Clock Is Ticking

Over the last decade we have come to understand the nature of psoriasis as a systemic inflammatory condition rather than as simply a skin disease. With this concept, we have continued to identify systemic comorbidities associated with psoriasis, including cardiovascular risk, diabetes mellitus, and metabolic syndrome. As dermatologists, we must serve as the gatekeeper for our patients with psoriasis and help to screen for comorbidities as well as provide appropriate counseling and referral.

Of the potential benefits of novel systemic therapies for psoriasis, the potential for addressing comorbid conditions with these treatments is critically important. Therefore, when I discuss psoriasis treatments, I always review and emphasize the anti-inflammatory effects of these agents. Although we know that psoriasis increases the risk for vascular inflammation and major adverse cardiovascular events (MACEs), it has been unclear if psoriasis duration affects these risks.

Egeberg et al1 utilized 2 resources to understand the effect of psoriasis duration on vascular disease and cardiovascular events: a human imaging study and a population-based study of cardiovascular disease events. In the first part of the study, patients with psoriasis (N=190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography. Next, MACE risk was examined using nationwide registries (adjusted hazard ratio in patients with psoriasis [n=87,161] vs the general population [n=4,234,793]). In the imaging study, participants had low cardiovascular risk by traditional risk scores. The authors found that vascular inflammation as demonstrated by the imaging system was significantly associated with disease duration (β=.171; P=.002). In the population-based study, psoriasis duration had a strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). The researchers reported that every standard deviation increase in disease duration increased the target-to-background ratio by 2.5%, which translated into an absolute increase of approximately 10% in future adverse events.1

Therefore, the authors concluded that there were negative effects of psoriasis duration on vascular inflammation and MACEs,1 which suggests that the cumulative duration of low-grade chronic inflammation may accelerate vascular disease development and MACEs. The authors therefore noted that providers should consider inquiring about duration of disease to counsel for heightened cardiovascular disease risk in psoriasis patients.1

We have some evidence that therapeutic intervention may be useful. Wu et al2 compared MACE risk in psoriasis patients receiving methotrexate or tumor necrosis factor α (TNF-α) inhibitors. They also assessed the impact of TNF-α inhibitor treatment duration on MACE risk. The authors concluded that psoriasis patients receiving TNF-α inhibitors had a lower MACE risk compared to those receiving methotrexate. Cumulative exposure to TNF-α inhibitors was associated with a reduced risk for MACEs.2

The findings of these studies are poignant and help to further emphasize the importance of proper identification and treatment of psoriasis and its comorbidities. This information also adds an element of urgency to the way we look at this disease and demonstrates that we must intervene as soon as possible in this process.

References
  1. Egeberg A, Skov L, Joshi AA, et al. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events [published online August 18, 2017]. J Am Acad Dermatol. 2017;77:650.e3-656.e3.
  2. Wu JJ, Guerin AD, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate [published online October 26, 2016]. J Am Acad Dermatol. 2017;76:81-90.
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Correspondence: Jeffrey M. Weinberg, MD, 10 Union Square E, Ste 3C, New York, NY 10003 ([email protected]).

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Correspondence: Jeffrey M. Weinberg, MD, 10 Union Square E, Ste 3C, New York, NY 10003 ([email protected]).

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Over the last decade we have come to understand the nature of psoriasis as a systemic inflammatory condition rather than as simply a skin disease. With this concept, we have continued to identify systemic comorbidities associated with psoriasis, including cardiovascular risk, diabetes mellitus, and metabolic syndrome. As dermatologists, we must serve as the gatekeeper for our patients with psoriasis and help to screen for comorbidities as well as provide appropriate counseling and referral.

Of the potential benefits of novel systemic therapies for psoriasis, the potential for addressing comorbid conditions with these treatments is critically important. Therefore, when I discuss psoriasis treatments, I always review and emphasize the anti-inflammatory effects of these agents. Although we know that psoriasis increases the risk for vascular inflammation and major adverse cardiovascular events (MACEs), it has been unclear if psoriasis duration affects these risks.

Egeberg et al1 utilized 2 resources to understand the effect of psoriasis duration on vascular disease and cardiovascular events: a human imaging study and a population-based study of cardiovascular disease events. In the first part of the study, patients with psoriasis (N=190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography. Next, MACE risk was examined using nationwide registries (adjusted hazard ratio in patients with psoriasis [n=87,161] vs the general population [n=4,234,793]). In the imaging study, participants had low cardiovascular risk by traditional risk scores. The authors found that vascular inflammation as demonstrated by the imaging system was significantly associated with disease duration (β=.171; P=.002). In the population-based study, psoriasis duration had a strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). The researchers reported that every standard deviation increase in disease duration increased the target-to-background ratio by 2.5%, which translated into an absolute increase of approximately 10% in future adverse events.1

Therefore, the authors concluded that there were negative effects of psoriasis duration on vascular inflammation and MACEs,1 which suggests that the cumulative duration of low-grade chronic inflammation may accelerate vascular disease development and MACEs. The authors therefore noted that providers should consider inquiring about duration of disease to counsel for heightened cardiovascular disease risk in psoriasis patients.1

We have some evidence that therapeutic intervention may be useful. Wu et al2 compared MACE risk in psoriasis patients receiving methotrexate or tumor necrosis factor α (TNF-α) inhibitors. They also assessed the impact of TNF-α inhibitor treatment duration on MACE risk. The authors concluded that psoriasis patients receiving TNF-α inhibitors had a lower MACE risk compared to those receiving methotrexate. Cumulative exposure to TNF-α inhibitors was associated with a reduced risk for MACEs.2

The findings of these studies are poignant and help to further emphasize the importance of proper identification and treatment of psoriasis and its comorbidities. This information also adds an element of urgency to the way we look at this disease and demonstrates that we must intervene as soon as possible in this process.

Over the last decade we have come to understand the nature of psoriasis as a systemic inflammatory condition rather than as simply a skin disease. With this concept, we have continued to identify systemic comorbidities associated with psoriasis, including cardiovascular risk, diabetes mellitus, and metabolic syndrome. As dermatologists, we must serve as the gatekeeper for our patients with psoriasis and help to screen for comorbidities as well as provide appropriate counseling and referral.

Of the potential benefits of novel systemic therapies for psoriasis, the potential for addressing comorbid conditions with these treatments is critically important. Therefore, when I discuss psoriasis treatments, I always review and emphasize the anti-inflammatory effects of these agents. Although we know that psoriasis increases the risk for vascular inflammation and major adverse cardiovascular events (MACEs), it has been unclear if psoriasis duration affects these risks.

Egeberg et al1 utilized 2 resources to understand the effect of psoriasis duration on vascular disease and cardiovascular events: a human imaging study and a population-based study of cardiovascular disease events. In the first part of the study, patients with psoriasis (N=190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography. Next, MACE risk was examined using nationwide registries (adjusted hazard ratio in patients with psoriasis [n=87,161] vs the general population [n=4,234,793]). In the imaging study, participants had low cardiovascular risk by traditional risk scores. The authors found that vascular inflammation as demonstrated by the imaging system was significantly associated with disease duration (β=.171; P=.002). In the population-based study, psoriasis duration had a strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). The researchers reported that every standard deviation increase in disease duration increased the target-to-background ratio by 2.5%, which translated into an absolute increase of approximately 10% in future adverse events.1

Therefore, the authors concluded that there were negative effects of psoriasis duration on vascular inflammation and MACEs,1 which suggests that the cumulative duration of low-grade chronic inflammation may accelerate vascular disease development and MACEs. The authors therefore noted that providers should consider inquiring about duration of disease to counsel for heightened cardiovascular disease risk in psoriasis patients.1

We have some evidence that therapeutic intervention may be useful. Wu et al2 compared MACE risk in psoriasis patients receiving methotrexate or tumor necrosis factor α (TNF-α) inhibitors. They also assessed the impact of TNF-α inhibitor treatment duration on MACE risk. The authors concluded that psoriasis patients receiving TNF-α inhibitors had a lower MACE risk compared to those receiving methotrexate. Cumulative exposure to TNF-α inhibitors was associated with a reduced risk for MACEs.2

The findings of these studies are poignant and help to further emphasize the importance of proper identification and treatment of psoriasis and its comorbidities. This information also adds an element of urgency to the way we look at this disease and demonstrates that we must intervene as soon as possible in this process.

References
  1. Egeberg A, Skov L, Joshi AA, et al. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events [published online August 18, 2017]. J Am Acad Dermatol. 2017;77:650.e3-656.e3.
  2. Wu JJ, Guerin AD, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate [published online October 26, 2016]. J Am Acad Dermatol. 2017;76:81-90.
References
  1. Egeberg A, Skov L, Joshi AA, et al. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events [published online August 18, 2017]. J Am Acad Dermatol. 2017;77:650.e3-656.e3.
  2. Wu JJ, Guerin AD, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate [published online October 26, 2016]. J Am Acad Dermatol. 2017;76:81-90.
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A Review of Neurologic Complications of Biologic Therapy in Plaque Psoriasis

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A Review of Neurologic Complications of Biologic Therapy in Plaque Psoriasis

Biologic agents have provided patients with moderate to severe psoriasis with treatment alternatives that have improved systemic safety profiles and disease control1; however, case reports of associated neurologic complications have been emerging. Tumor necrosis factor α (TNF-α) inhibitors have been associated with central and peripheral demyelinating disorders. Notably, efalizumab was withdrawn from the market for its association with fatal cases of progressive multifocal leukoencephalopathy (PML).2,3 It is imperative for dermatologists to be familiar with the clinical presentation, evaluation, and diagnostic criteria of neurologic complications of biologic agents used in the treatment of psoriasis.

Leukoencephalopathy

Progressive multifocal leukoencephalopathy is a fatal demyelinating neurodegenerative disease caused by reactivation of the ubiquitous John Cunningham virus. Primary asymptomatic infection is thought to occur during childhood, then the virus remains latent. Reactivation usually occurs during severe immunosuppression and is classically described in human immunodeficiency virus infection, lymphoproliferative disorders, and other forms of cancer.4 A summary of PML and its association with biologics is found in Table 1.5-13 Few case reports of TNF-α inhibitor–associated PML exist, mostly in the presence of confounding factors such as immunosuppression or underlying autoimmune disease.10-13 Presenting symptoms of PML often are subacute, rapidly progressive, and can be focal or multifocal and include motor, cognitive, and visual deficits. Of note, there are 2 reported cases of ustekinumab associated with reversible posterior leukoencephalopathy syndrome, which is a hypertensive encephalopathy characterized by headache, altered mental status, vision abnormalities, and seizures.14,15 Fortunately, this disease is reversible with blood pressure control and removal of the immunosuppressive agent.16

Demyelinating Disorders

Clinical presentation of demyelinating events associated with biologic agents are varied but include optic neuritis, multiple sclerosis, transverse myelitis, and Guillain-Barré syndrome, among others.17-28 These demyelinating disorders with their salient features and associated biologics are summarized in Table 2.17-20,22-28 Patients on biologic agents, especially TNF-α inhibitors, with new-onset visual, motor, or sensory changes warrant closer inspection. Currently, there are no data on any neurologic side effects occurring with the new biologic secukinumab.29

Conclusion

Biologic agents are effective in treating moderate to severe plaque psoriasis, but awareness of associated neurological adverse effects, though rare, is important to consider. Physicians need to be able to counsel patients concerning these risks and promote informed decision-making prior to initiating biologics. Patients with a personal or strong family history of demyelinating disease should be considered for alternative treatment options before initiating anti–TNF-α therapy. Since the withdrawal of efalizumab, no new cases of PML have been reported in patients who were previously on a long-term course. Dermatologists should be vigilant in detecting signs of neurological complications so that an expedited evaluation and neurology referral may prevent progression of disease.

References
  1. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
  2. FDA Statement on the Voluntary Withdrawal of Raptiva From the U.S. Market. US Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrug-SafetyInformationforPatientsandProviders/ucm143347.htm. Published April 8, 2009. Accessed December 21, 2017.
  3. Kothary N, Diak IL, Brinker A, et al. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol. 2011;65:546-551.
  4. Tavazzi E, Ferrante P, Khalili K. Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies. Clin Microbiol Infect. 2011;17:1776-1780.
  5. Korman BD, Tyler KL, Korman NJ. Progressive multifocal leukoencephalopathy, efalizumab, and immunosuppression: a cautionary tale for dermatologists. Arch Dermatol. 2009;145:937-942.
  6. Sudhakar P, Bachman DM, Mark AS, et al. Progressive multifocal leukoencephalopathy: recent advances and a neuro-ophthalmological review. J Neuroophthalmol. 2015;35:296-305.
  7. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013;80:1430-1438.
  8. Koralnik IJ, Boden D, Mai VX, et al. JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy. Neurology. 1999;52:253-260.
  9. Clifford DB, Ances B, Costello C, et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol. 2011;68:1156-1164.
  10. Babi MA, Pendlebury W, Braff S, et al. JC virus PCR detection is not infallible: a fulminant case of progressive multifocal leukoencephalopathy with false-negative cerebrospinal fluid studies despite progressive clinical course and radiological findings [published online March 12, 2015]. Case Rep Neurol Med. 2015;2015:643216.
  11. Ray M, Curtis JR, Baddley JW. A case report of progressive multifocal leucoencephalopathy (PML) associated with adalimumab. Ann Rheum Dis. 2014;73:1429-1430.
  12. Kumar D, Bouldin TW, Berger RG. A case of progressive multifocal leukoencephalopathy in a patient treated with infliximab. Arthritis Rheum. 2010;62:3191-3195.
  13. Graff-Radford J, Robinson MT, Warsame RM, et al. Progressive multifocal leukoencephalopathy in a patient treated with etanercept. Neurologist. 2012;18:85-87.
  14. Dickson L, Menter A. Reversible posterior leukoencephalopathy syndrome (RPLS) in a psoriasis patient treated with ustekinumab. J Drugs Dermatol. 2017;16:177-179.
  15. Gratton D, Szapary P, Goyal K, et al. Reversible posterior leukoencephalopathy syndrome in a patient treated with ustekinumab: case report and review of the literature. Arch Dermatol. 2011;147:1197-1202.
  16. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334:494-500.
  17. Ramos-Casals M, Roberto-Perez A, Diaz-Lagares C, et al. Autoimmune diseases induced by biological agents: a double-edged sword? Autoimmun Rev. 2010;9:188-193.
  18. Hoorbakht H, Bagherkashi F. Optic neuritis, its differential diagnosis and management. Open Ophthalmol J. 2012;6:65-72.
  19. Richards RG, Sampson FC, Beard SM, et al. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess. 2002;6:1-73.
  20. Caracseghi F, Izquierdo-Blasco J, Sanchez-Montanez A, et al. Etanercept-induced myelopathy in a pediatric case of blau syndrome [published online January 15, 2012]. Case Rep Rheumatol. 2011;2011:134106.
  21. Fromont A, De Seze J, Fleury MC, et al. Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine. 2009;45:55-57.
  22. Sellner J, Lüthi N, Schüpbach WM, et al. Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings. Spinal Cord. 2009;47:312-317.
  23. Turatti M, Tamburin S, Idone D, et al. Guillain-Barré syndrome after short-course efalizumab treatment. J Neurol. 2010;257:1404-1405.
  24. Koga M, Yuki N, Hirata K. Antecedent symptoms in Guillain-Barré syndrome: an important indicator for clinical and serological subgroups. Acta Neurol Scand. 2001;103:278-287.
  25. Cesarini M, Angelucci E, Foglietta T, et al. Guillain-Barré syndrome after treatment with human anti-tumor necrosis factor alpha (adalimumab) in a Crohn’s disease patient: case report and literature review [published online July 28, 2011]. J Crohns Colitis. 2011;5:619-622.
  26. Soto-Cabrera E, Hernández-Martínez A, Yañez H, et al. Guillain-Barré syndrome. Its association with alpha tumor necrosis factor [in Spanish]. Rev Med Inst Mex Seguro Soc. 2012;50:565-567.
  27. Shin IS, Baer AN, Kwon HJ, et al. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy. Arthritis Rheum. 2006;54:1429-1434.
  28. Alvarez-Lario B, Prieto-Tejedo R, Colazo-Burlato M, et al. Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. consequence or coincidence. a case-based review. Clin Rheumatol. 2013;32:1407-1412.
  29. Garnock-Jones KP. Secukinumab: a review in moderate to severe plaque psoriasis. Am J Clin Dermatol. 2015;16:323-330.
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Drs. Lin, Reddy, and Shah report no conflict of interest. Dr. Wu is an investigator for AbbVie Inc; Amgen Inc; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; and Regeneron Pharmaceuticals, Inc.

Correspondence: Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Department of Dermatology, 1515 N Vermont Ave, 5th Floor, Los Angeles, CA 90027 ([email protected]).

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Drs. Lin, Reddy, and Shah report no conflict of interest. Dr. Wu is an investigator for AbbVie Inc; Amgen Inc; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; and Regeneron Pharmaceuticals, Inc.

Correspondence: Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Department of Dermatology, 1515 N Vermont Ave, 5th Floor, Los Angeles, CA 90027 ([email protected]).

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Dr. Lin is from Olive View-UCLA Medical Center, Department of Internal Medicine, Sylmar, California. Dr. Reddy is from the School of Medicine, University of Illinois at Chicago. Dr. Shah is from the School of Medicine, University of Missouri-Kansas City. Dr. Wu is from the Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, California.

Drs. Lin, Reddy, and Shah report no conflict of interest. Dr. Wu is an investigator for AbbVie Inc; Amgen Inc; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; and Regeneron Pharmaceuticals, Inc.

Correspondence: Jashin J. Wu, MD, Kaiser Permanente Los Angeles Medical Center, Department of Dermatology, 1515 N Vermont Ave, 5th Floor, Los Angeles, CA 90027 ([email protected]).

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Biologic agents have provided patients with moderate to severe psoriasis with treatment alternatives that have improved systemic safety profiles and disease control1; however, case reports of associated neurologic complications have been emerging. Tumor necrosis factor α (TNF-α) inhibitors have been associated with central and peripheral demyelinating disorders. Notably, efalizumab was withdrawn from the market for its association with fatal cases of progressive multifocal leukoencephalopathy (PML).2,3 It is imperative for dermatologists to be familiar with the clinical presentation, evaluation, and diagnostic criteria of neurologic complications of biologic agents used in the treatment of psoriasis.

Leukoencephalopathy

Progressive multifocal leukoencephalopathy is a fatal demyelinating neurodegenerative disease caused by reactivation of the ubiquitous John Cunningham virus. Primary asymptomatic infection is thought to occur during childhood, then the virus remains latent. Reactivation usually occurs during severe immunosuppression and is classically described in human immunodeficiency virus infection, lymphoproliferative disorders, and other forms of cancer.4 A summary of PML and its association with biologics is found in Table 1.5-13 Few case reports of TNF-α inhibitor–associated PML exist, mostly in the presence of confounding factors such as immunosuppression or underlying autoimmune disease.10-13 Presenting symptoms of PML often are subacute, rapidly progressive, and can be focal or multifocal and include motor, cognitive, and visual deficits. Of note, there are 2 reported cases of ustekinumab associated with reversible posterior leukoencephalopathy syndrome, which is a hypertensive encephalopathy characterized by headache, altered mental status, vision abnormalities, and seizures.14,15 Fortunately, this disease is reversible with blood pressure control and removal of the immunosuppressive agent.16

Demyelinating Disorders

Clinical presentation of demyelinating events associated with biologic agents are varied but include optic neuritis, multiple sclerosis, transverse myelitis, and Guillain-Barré syndrome, among others.17-28 These demyelinating disorders with their salient features and associated biologics are summarized in Table 2.17-20,22-28 Patients on biologic agents, especially TNF-α inhibitors, with new-onset visual, motor, or sensory changes warrant closer inspection. Currently, there are no data on any neurologic side effects occurring with the new biologic secukinumab.29

Conclusion

Biologic agents are effective in treating moderate to severe plaque psoriasis, but awareness of associated neurological adverse effects, though rare, is important to consider. Physicians need to be able to counsel patients concerning these risks and promote informed decision-making prior to initiating biologics. Patients with a personal or strong family history of demyelinating disease should be considered for alternative treatment options before initiating anti–TNF-α therapy. Since the withdrawal of efalizumab, no new cases of PML have been reported in patients who were previously on a long-term course. Dermatologists should be vigilant in detecting signs of neurological complications so that an expedited evaluation and neurology referral may prevent progression of disease.

Biologic agents have provided patients with moderate to severe psoriasis with treatment alternatives that have improved systemic safety profiles and disease control1; however, case reports of associated neurologic complications have been emerging. Tumor necrosis factor α (TNF-α) inhibitors have been associated with central and peripheral demyelinating disorders. Notably, efalizumab was withdrawn from the market for its association with fatal cases of progressive multifocal leukoencephalopathy (PML).2,3 It is imperative for dermatologists to be familiar with the clinical presentation, evaluation, and diagnostic criteria of neurologic complications of biologic agents used in the treatment of psoriasis.

Leukoencephalopathy

Progressive multifocal leukoencephalopathy is a fatal demyelinating neurodegenerative disease caused by reactivation of the ubiquitous John Cunningham virus. Primary asymptomatic infection is thought to occur during childhood, then the virus remains latent. Reactivation usually occurs during severe immunosuppression and is classically described in human immunodeficiency virus infection, lymphoproliferative disorders, and other forms of cancer.4 A summary of PML and its association with biologics is found in Table 1.5-13 Few case reports of TNF-α inhibitor–associated PML exist, mostly in the presence of confounding factors such as immunosuppression or underlying autoimmune disease.10-13 Presenting symptoms of PML often are subacute, rapidly progressive, and can be focal or multifocal and include motor, cognitive, and visual deficits. Of note, there are 2 reported cases of ustekinumab associated with reversible posterior leukoencephalopathy syndrome, which is a hypertensive encephalopathy characterized by headache, altered mental status, vision abnormalities, and seizures.14,15 Fortunately, this disease is reversible with blood pressure control and removal of the immunosuppressive agent.16

Demyelinating Disorders

Clinical presentation of demyelinating events associated with biologic agents are varied but include optic neuritis, multiple sclerosis, transverse myelitis, and Guillain-Barré syndrome, among others.17-28 These demyelinating disorders with their salient features and associated biologics are summarized in Table 2.17-20,22-28 Patients on biologic agents, especially TNF-α inhibitors, with new-onset visual, motor, or sensory changes warrant closer inspection. Currently, there are no data on any neurologic side effects occurring with the new biologic secukinumab.29

Conclusion

Biologic agents are effective in treating moderate to severe plaque psoriasis, but awareness of associated neurological adverse effects, though rare, is important to consider. Physicians need to be able to counsel patients concerning these risks and promote informed decision-making prior to initiating biologics. Patients with a personal or strong family history of demyelinating disease should be considered for alternative treatment options before initiating anti–TNF-α therapy. Since the withdrawal of efalizumab, no new cases of PML have been reported in patients who were previously on a long-term course. Dermatologists should be vigilant in detecting signs of neurological complications so that an expedited evaluation and neurology referral may prevent progression of disease.

References
  1. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
  2. FDA Statement on the Voluntary Withdrawal of Raptiva From the U.S. Market. US Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrug-SafetyInformationforPatientsandProviders/ucm143347.htm. Published April 8, 2009. Accessed December 21, 2017.
  3. Kothary N, Diak IL, Brinker A, et al. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol. 2011;65:546-551.
  4. Tavazzi E, Ferrante P, Khalili K. Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies. Clin Microbiol Infect. 2011;17:1776-1780.
  5. Korman BD, Tyler KL, Korman NJ. Progressive multifocal leukoencephalopathy, efalizumab, and immunosuppression: a cautionary tale for dermatologists. Arch Dermatol. 2009;145:937-942.
  6. Sudhakar P, Bachman DM, Mark AS, et al. Progressive multifocal leukoencephalopathy: recent advances and a neuro-ophthalmological review. J Neuroophthalmol. 2015;35:296-305.
  7. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013;80:1430-1438.
  8. Koralnik IJ, Boden D, Mai VX, et al. JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy. Neurology. 1999;52:253-260.
  9. Clifford DB, Ances B, Costello C, et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol. 2011;68:1156-1164.
  10. Babi MA, Pendlebury W, Braff S, et al. JC virus PCR detection is not infallible: a fulminant case of progressive multifocal leukoencephalopathy with false-negative cerebrospinal fluid studies despite progressive clinical course and radiological findings [published online March 12, 2015]. Case Rep Neurol Med. 2015;2015:643216.
  11. Ray M, Curtis JR, Baddley JW. A case report of progressive multifocal leucoencephalopathy (PML) associated with adalimumab. Ann Rheum Dis. 2014;73:1429-1430.
  12. Kumar D, Bouldin TW, Berger RG. A case of progressive multifocal leukoencephalopathy in a patient treated with infliximab. Arthritis Rheum. 2010;62:3191-3195.
  13. Graff-Radford J, Robinson MT, Warsame RM, et al. Progressive multifocal leukoencephalopathy in a patient treated with etanercept. Neurologist. 2012;18:85-87.
  14. Dickson L, Menter A. Reversible posterior leukoencephalopathy syndrome (RPLS) in a psoriasis patient treated with ustekinumab. J Drugs Dermatol. 2017;16:177-179.
  15. Gratton D, Szapary P, Goyal K, et al. Reversible posterior leukoencephalopathy syndrome in a patient treated with ustekinumab: case report and review of the literature. Arch Dermatol. 2011;147:1197-1202.
  16. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334:494-500.
  17. Ramos-Casals M, Roberto-Perez A, Diaz-Lagares C, et al. Autoimmune diseases induced by biological agents: a double-edged sword? Autoimmun Rev. 2010;9:188-193.
  18. Hoorbakht H, Bagherkashi F. Optic neuritis, its differential diagnosis and management. Open Ophthalmol J. 2012;6:65-72.
  19. Richards RG, Sampson FC, Beard SM, et al. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess. 2002;6:1-73.
  20. Caracseghi F, Izquierdo-Blasco J, Sanchez-Montanez A, et al. Etanercept-induced myelopathy in a pediatric case of blau syndrome [published online January 15, 2012]. Case Rep Rheumatol. 2011;2011:134106.
  21. Fromont A, De Seze J, Fleury MC, et al. Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine. 2009;45:55-57.
  22. Sellner J, Lüthi N, Schüpbach WM, et al. Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings. Spinal Cord. 2009;47:312-317.
  23. Turatti M, Tamburin S, Idone D, et al. Guillain-Barré syndrome after short-course efalizumab treatment. J Neurol. 2010;257:1404-1405.
  24. Koga M, Yuki N, Hirata K. Antecedent symptoms in Guillain-Barré syndrome: an important indicator for clinical and serological subgroups. Acta Neurol Scand. 2001;103:278-287.
  25. Cesarini M, Angelucci E, Foglietta T, et al. Guillain-Barré syndrome after treatment with human anti-tumor necrosis factor alpha (adalimumab) in a Crohn’s disease patient: case report and literature review [published online July 28, 2011]. J Crohns Colitis. 2011;5:619-622.
  26. Soto-Cabrera E, Hernández-Martínez A, Yañez H, et al. Guillain-Barré syndrome. Its association with alpha tumor necrosis factor [in Spanish]. Rev Med Inst Mex Seguro Soc. 2012;50:565-567.
  27. Shin IS, Baer AN, Kwon HJ, et al. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy. Arthritis Rheum. 2006;54:1429-1434.
  28. Alvarez-Lario B, Prieto-Tejedo R, Colazo-Burlato M, et al. Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. consequence or coincidence. a case-based review. Clin Rheumatol. 2013;32:1407-1412.
  29. Garnock-Jones KP. Secukinumab: a review in moderate to severe plaque psoriasis. Am J Clin Dermatol. 2015;16:323-330.
References
  1. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
  2. FDA Statement on the Voluntary Withdrawal of Raptiva From the U.S. Market. US Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrug-SafetyInformationforPatientsandProviders/ucm143347.htm. Published April 8, 2009. Accessed December 21, 2017.
  3. Kothary N, Diak IL, Brinker A, et al. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol. 2011;65:546-551.
  4. Tavazzi E, Ferrante P, Khalili K. Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies. Clin Microbiol Infect. 2011;17:1776-1780.
  5. Korman BD, Tyler KL, Korman NJ. Progressive multifocal leukoencephalopathy, efalizumab, and immunosuppression: a cautionary tale for dermatologists. Arch Dermatol. 2009;145:937-942.
  6. Sudhakar P, Bachman DM, Mark AS, et al. Progressive multifocal leukoencephalopathy: recent advances and a neuro-ophthalmological review. J Neuroophthalmol. 2015;35:296-305.
  7. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013;80:1430-1438.
  8. Koralnik IJ, Boden D, Mai VX, et al. JC virus DNA load in patients with and without progressive multifocal leukoencephalopathy. Neurology. 1999;52:253-260.
  9. Clifford DB, Ances B, Costello C, et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol. 2011;68:1156-1164.
  10. Babi MA, Pendlebury W, Braff S, et al. JC virus PCR detection is not infallible: a fulminant case of progressive multifocal leukoencephalopathy with false-negative cerebrospinal fluid studies despite progressive clinical course and radiological findings [published online March 12, 2015]. Case Rep Neurol Med. 2015;2015:643216.
  11. Ray M, Curtis JR, Baddley JW. A case report of progressive multifocal leucoencephalopathy (PML) associated with adalimumab. Ann Rheum Dis. 2014;73:1429-1430.
  12. Kumar D, Bouldin TW, Berger RG. A case of progressive multifocal leukoencephalopathy in a patient treated with infliximab. Arthritis Rheum. 2010;62:3191-3195.
  13. Graff-Radford J, Robinson MT, Warsame RM, et al. Progressive multifocal leukoencephalopathy in a patient treated with etanercept. Neurologist. 2012;18:85-87.
  14. Dickson L, Menter A. Reversible posterior leukoencephalopathy syndrome (RPLS) in a psoriasis patient treated with ustekinumab. J Drugs Dermatol. 2017;16:177-179.
  15. Gratton D, Szapary P, Goyal K, et al. Reversible posterior leukoencephalopathy syndrome in a patient treated with ustekinumab: case report and review of the literature. Arch Dermatol. 2011;147:1197-1202.
  16. Hinchey J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334:494-500.
  17. Ramos-Casals M, Roberto-Perez A, Diaz-Lagares C, et al. Autoimmune diseases induced by biological agents: a double-edged sword? Autoimmun Rev. 2010;9:188-193.
  18. Hoorbakht H, Bagherkashi F. Optic neuritis, its differential diagnosis and management. Open Ophthalmol J. 2012;6:65-72.
  19. Richards RG, Sampson FC, Beard SM, et al. A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models. Health Technol Assess. 2002;6:1-73.
  20. Caracseghi F, Izquierdo-Blasco J, Sanchez-Montanez A, et al. Etanercept-induced myelopathy in a pediatric case of blau syndrome [published online January 15, 2012]. Case Rep Rheumatol. 2011;2011:134106.
  21. Fromont A, De Seze J, Fleury MC, et al. Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. Cytokine. 2009;45:55-57.
  22. Sellner J, Lüthi N, Schüpbach WM, et al. Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings. Spinal Cord. 2009;47:312-317.
  23. Turatti M, Tamburin S, Idone D, et al. Guillain-Barré syndrome after short-course efalizumab treatment. J Neurol. 2010;257:1404-1405.
  24. Koga M, Yuki N, Hirata K. Antecedent symptoms in Guillain-Barré syndrome: an important indicator for clinical and serological subgroups. Acta Neurol Scand. 2001;103:278-287.
  25. Cesarini M, Angelucci E, Foglietta T, et al. Guillain-Barré syndrome after treatment with human anti-tumor necrosis factor alpha (adalimumab) in a Crohn’s disease patient: case report and literature review [published online July 28, 2011]. J Crohns Colitis. 2011;5:619-622.
  26. Soto-Cabrera E, Hernández-Martínez A, Yañez H, et al. Guillain-Barré syndrome. Its association with alpha tumor necrosis factor [in Spanish]. Rev Med Inst Mex Seguro Soc. 2012;50:565-567.
  27. Shin IS, Baer AN, Kwon HJ, et al. Guillain-Barré and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy. Arthritis Rheum. 2006;54:1429-1434.
  28. Alvarez-Lario B, Prieto-Tejedo R, Colazo-Burlato M, et al. Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. consequence or coincidence. a case-based review. Clin Rheumatol. 2013;32:1407-1412.
  29. Garnock-Jones KP. Secukinumab: a review in moderate to severe plaque psoriasis. Am J Clin Dermatol. 2015;16:323-330.
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Practice Points

  • Patients with a personal or strong family history of demyelinating disease should be considered for alternative treatment options before initiating anti–tumor necrosis factor (TNF) α therapy.
  • Patients on biologic agents, especially TNF-α inhibitors, with subacute or rapidly progressive visual, motor, or sensory changes or a single neurologic deficit may warrant referral to neurology and/or neuroimaging.
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Minorities less likely to seek treatment for psoriasis

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Black, Asian, and other non-Hispanic Americans are less likely than are whites to seek treatment for psoriasis, according to data on 842 patients, reported Alexander H. Fischer, MD, of the University of Pennsylvania, Philadelphia, and his colleagues.

Data from previous studies have shown that racial and ethnic minorities have more severe psoriasis and a lower quality of life as a result of the disease, compared with white patients, the researchers noted in a study published as a research letter in the Journal of the American Academy of Dermatology.

Penn Medicine
Dr. Junko Takeshita
They reviewed data from the Medical Expenditure Panel Survey on health care utilization, cost, and insurance coverage in the United States from 2001 through 2013.

A total of 51% of non-Hispanic whites with psoriasis sought treatment from a dermatologist, compared with 47% of Hispanic whites and 38% of non-Hispanic minorities (blacks, Asians, native Hawaiians, Pacific Islanders, and others). In addition, non-Hispanic minorities had significantly fewer ambulatory visits for psoriasis per year than did whites (a mean of 1.30 visits vs. 2.69 visits). Black, Asian, and other non-Hispanic minorities were about 40% less likely than were non-Hispanic whites to seek care for psoriasis.

The number of psoriasis prescriptions obtained was not significantly different among the racial/ethnic groups, the researchers reported.

The study is important because of the lack of data on psoriasis in nonwhite populations, senior author Junko Takeshita, MD, PhD, also of the University of Pennsylvania, said in an interview.

“Based on a few existing studies, we know that psoriasis is less common among minorities, but minorities, particularly blacks, may have more severe disease,” she said. “Also, minorities report poorer quality of life due to psoriasis than whites, independent of psoriasis severity. Furthermore, we previously published a study among Medicare beneficiaries with psoriasis that revealed that blacks are about 70% less likely to receive biologic therapies than whites, independent of socioeconomic status and access to medical care,” she added.

“The take-home message for clinicians is that while psoriasis is less common among minorities than whites, minorities may suffer from a larger burden of disease, yet have fewer visits and are less likely to see a dermatologist for their psoriasis,” Dr. Takeshita said. “This disparity in health care utilization for psoriasis does not seem to be entirely explained by racial/ethnic differences in socioeconomic status and health insurance. It is yet unknown why this disparity exists, and I’m not sure that minority patients being ‘hesitant to pursue care’ is the entire answer, though it may be a contributing factor,” she noted.

The study findings were limited by several factors including the relatively small sample size and the use of self-reports.

Many factors could be contributing to the disparity, including patient, physician/other health care provider, and health care system factors, but “once we identify the major causes of the disparity, we can develop methods to address the causes and reduce the disparity,” said Dr. Takeshita, who is a dermatologist and an epidemiologist. In the meantime, she added, “some things I think that are important to ensure equitable care for psoriasis are making sure that clinicians/dermatologists are comfortable diagnosing and treating psoriasis in nonwhite individuals, and encouraging clinicians to help increase awareness of psoriasis by educating their minority patients that psoriasis is still a common skin disease among nonwhite individuals.”

The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Takeshita has received a research grant from Pfizer; she and another author, Joel Gelfand, MD, have received payment for psoriasis-related continuing medical education work supported indirectly by Eli Lilly; Dr. Gelfand’s other disclosures included serving as a consultant for, and having received research grants from, several other pharmaceutical companies. Dr. Fischer, a medical student at Johns Hopkins University, Baltimore, at the time of the research, and a fourth author had no financial disclosures.

SOURCE: Fischer AH et al. J Am Acad Dermatol. 2018 Jan;78[1]:200-3. doi: 10.1016/j.jaad.2017.07.052.

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Black, Asian, and other non-Hispanic Americans are less likely than are whites to seek treatment for psoriasis, according to data on 842 patients, reported Alexander H. Fischer, MD, of the University of Pennsylvania, Philadelphia, and his colleagues.

Data from previous studies have shown that racial and ethnic minorities have more severe psoriasis and a lower quality of life as a result of the disease, compared with white patients, the researchers noted in a study published as a research letter in the Journal of the American Academy of Dermatology.

Penn Medicine
Dr. Junko Takeshita
They reviewed data from the Medical Expenditure Panel Survey on health care utilization, cost, and insurance coverage in the United States from 2001 through 2013.

A total of 51% of non-Hispanic whites with psoriasis sought treatment from a dermatologist, compared with 47% of Hispanic whites and 38% of non-Hispanic minorities (blacks, Asians, native Hawaiians, Pacific Islanders, and others). In addition, non-Hispanic minorities had significantly fewer ambulatory visits for psoriasis per year than did whites (a mean of 1.30 visits vs. 2.69 visits). Black, Asian, and other non-Hispanic minorities were about 40% less likely than were non-Hispanic whites to seek care for psoriasis.

The number of psoriasis prescriptions obtained was not significantly different among the racial/ethnic groups, the researchers reported.

The study is important because of the lack of data on psoriasis in nonwhite populations, senior author Junko Takeshita, MD, PhD, also of the University of Pennsylvania, said in an interview.

“Based on a few existing studies, we know that psoriasis is less common among minorities, but minorities, particularly blacks, may have more severe disease,” she said. “Also, minorities report poorer quality of life due to psoriasis than whites, independent of psoriasis severity. Furthermore, we previously published a study among Medicare beneficiaries with psoriasis that revealed that blacks are about 70% less likely to receive biologic therapies than whites, independent of socioeconomic status and access to medical care,” she added.

“The take-home message for clinicians is that while psoriasis is less common among minorities than whites, minorities may suffer from a larger burden of disease, yet have fewer visits and are less likely to see a dermatologist for their psoriasis,” Dr. Takeshita said. “This disparity in health care utilization for psoriasis does not seem to be entirely explained by racial/ethnic differences in socioeconomic status and health insurance. It is yet unknown why this disparity exists, and I’m not sure that minority patients being ‘hesitant to pursue care’ is the entire answer, though it may be a contributing factor,” she noted.

The study findings were limited by several factors including the relatively small sample size and the use of self-reports.

Many factors could be contributing to the disparity, including patient, physician/other health care provider, and health care system factors, but “once we identify the major causes of the disparity, we can develop methods to address the causes and reduce the disparity,” said Dr. Takeshita, who is a dermatologist and an epidemiologist. In the meantime, she added, “some things I think that are important to ensure equitable care for psoriasis are making sure that clinicians/dermatologists are comfortable diagnosing and treating psoriasis in nonwhite individuals, and encouraging clinicians to help increase awareness of psoriasis by educating their minority patients that psoriasis is still a common skin disease among nonwhite individuals.”

The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Takeshita has received a research grant from Pfizer; she and another author, Joel Gelfand, MD, have received payment for psoriasis-related continuing medical education work supported indirectly by Eli Lilly; Dr. Gelfand’s other disclosures included serving as a consultant for, and having received research grants from, several other pharmaceutical companies. Dr. Fischer, a medical student at Johns Hopkins University, Baltimore, at the time of the research, and a fourth author had no financial disclosures.

SOURCE: Fischer AH et al. J Am Acad Dermatol. 2018 Jan;78[1]:200-3. doi: 10.1016/j.jaad.2017.07.052.

 

Black, Asian, and other non-Hispanic Americans are less likely than are whites to seek treatment for psoriasis, according to data on 842 patients, reported Alexander H. Fischer, MD, of the University of Pennsylvania, Philadelphia, and his colleagues.

Data from previous studies have shown that racial and ethnic minorities have more severe psoriasis and a lower quality of life as a result of the disease, compared with white patients, the researchers noted in a study published as a research letter in the Journal of the American Academy of Dermatology.

Penn Medicine
Dr. Junko Takeshita
They reviewed data from the Medical Expenditure Panel Survey on health care utilization, cost, and insurance coverage in the United States from 2001 through 2013.

A total of 51% of non-Hispanic whites with psoriasis sought treatment from a dermatologist, compared with 47% of Hispanic whites and 38% of non-Hispanic minorities (blacks, Asians, native Hawaiians, Pacific Islanders, and others). In addition, non-Hispanic minorities had significantly fewer ambulatory visits for psoriasis per year than did whites (a mean of 1.30 visits vs. 2.69 visits). Black, Asian, and other non-Hispanic minorities were about 40% less likely than were non-Hispanic whites to seek care for psoriasis.

The number of psoriasis prescriptions obtained was not significantly different among the racial/ethnic groups, the researchers reported.

The study is important because of the lack of data on psoriasis in nonwhite populations, senior author Junko Takeshita, MD, PhD, also of the University of Pennsylvania, said in an interview.

“Based on a few existing studies, we know that psoriasis is less common among minorities, but minorities, particularly blacks, may have more severe disease,” she said. “Also, minorities report poorer quality of life due to psoriasis than whites, independent of psoriasis severity. Furthermore, we previously published a study among Medicare beneficiaries with psoriasis that revealed that blacks are about 70% less likely to receive biologic therapies than whites, independent of socioeconomic status and access to medical care,” she added.

“The take-home message for clinicians is that while psoriasis is less common among minorities than whites, minorities may suffer from a larger burden of disease, yet have fewer visits and are less likely to see a dermatologist for their psoriasis,” Dr. Takeshita said. “This disparity in health care utilization for psoriasis does not seem to be entirely explained by racial/ethnic differences in socioeconomic status and health insurance. It is yet unknown why this disparity exists, and I’m not sure that minority patients being ‘hesitant to pursue care’ is the entire answer, though it may be a contributing factor,” she noted.

The study findings were limited by several factors including the relatively small sample size and the use of self-reports.

Many factors could be contributing to the disparity, including patient, physician/other health care provider, and health care system factors, but “once we identify the major causes of the disparity, we can develop methods to address the causes and reduce the disparity,” said Dr. Takeshita, who is a dermatologist and an epidemiologist. In the meantime, she added, “some things I think that are important to ensure equitable care for psoriasis are making sure that clinicians/dermatologists are comfortable diagnosing and treating psoriasis in nonwhite individuals, and encouraging clinicians to help increase awareness of psoriasis by educating their minority patients that psoriasis is still a common skin disease among nonwhite individuals.”

The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Takeshita has received a research grant from Pfizer; she and another author, Joel Gelfand, MD, have received payment for psoriasis-related continuing medical education work supported indirectly by Eli Lilly; Dr. Gelfand’s other disclosures included serving as a consultant for, and having received research grants from, several other pharmaceutical companies. Dr. Fischer, a medical student at Johns Hopkins University, Baltimore, at the time of the research, and a fourth author had no financial disclosures.

SOURCE: Fischer AH et al. J Am Acad Dermatol. 2018 Jan;78[1]:200-3. doi: 10.1016/j.jaad.2017.07.052.

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FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

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Key clinical point: Black, Asian, and non-Hispanic patients with psoriasis often have more severe disease than do white patients but are significantly less likely to seek care.

Major finding: Black, Asian, and other non-Hispanic Americans were 40% less likely than were whites to seek care for psoriasis.

Data source: A cohort study of data from the Medical Expenditure Panel Survey on 842 psoriasis patients in the United States.

Disclosures: The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two of the four authors had no financial disclosures. One author has received a research grant from Pfizer and payment for psoriasis-related continuing medical education work supported indirectly by Eli Lilly; another author’s disclosures included the latter, as well serving as a consultant for, and having received research grants from, several other pharmaceutical companies.

Source: Fischer AH et al. J Am Acad Dermatol. 2018 Jan;78[1]:200-3. doi: 10.1016/j.jaad.2017.07.05

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Debunking Psoriasis Myths: How to Help Patients Who Are Afraid of Injections

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Debunking Psoriasis Myths: How to Help Patients Who Are Afraid of Injections

Myth: Patients Are Not Willing to Give Themselves Injections

Injectable biologics target specific parts of the immune system, making them popular treatment options for psoriasis patients, with ample research on their efficacy. Performing a self-injection can be daunting for patients trying a biologic for the first time, and clinicians should be aware of the dearth of patient education material. Although patients may be fearful of self-injections, especially the first few treatments, their worries can be assuaged with proper instruction and appropriate delivery method.

Abrouk et al sought to provide an online guide and video on biologic injections to increase the success of the therapy and compliance among patients. They created a printable guide that covers the supplies needed, procedure techniques, and plans for traveling with medications. Because pain is a common concern for patients, they suggest numbing the injection area with an ice pack first. They also offer tips on dealing with injection-site reactions such as redness or bruising.

Nurse practitioners and physician assistants can be used to give psoriasis patients more personalized attention regarding the fear of injections. They can explain the injection procedures and describe differences between administration techniques. Some patients may prefer using an autoinjector versus a prefilled syringe, which may impact the treatment administered. Taking photographs to show progress with therapy also may motivate patients to tolerate therapy.

The National Psoriasis Foundation provides the following tips to make it easier for patients to self-inject and reduce the chance of an injection-site reaction:

  • Pick an easy injection site, such as the top of the rights, abdomen, or back of the arms.
  • Rotate injection sites from right to left.
  • Numb the area.
  • Warm the pen up by taking it out of the refrigerator 1.5 hours before it is used.
  • Be patient and avoid moving the injection pen before the needle is finished administering the drug.

By giving psoriasis patients educational materials, you can empower them to control their disease with injectable biologics.

Expert Commentary

Most of my patients who use a biologic for the first time are undaunted by learning to inject themselves. I can think of just 1 of my ~300 biologic patients who has to come in every few weeks for their medicine to be injected by one of our nurses. Surprisingly, some patients (I'd estimate 5% of my biologic patients) actually prefer the syringe compared to the autoinjector, with some comments saying that the syringe is less painful and less abrupt. Needle phobia should not be a reason to not prescribe a biologic for a patient with severe psoriasis who needs it.

—Jashin J. Wu, MD (Los Angeles, California)

References

Abrouk M, Nakamura M, Zhu TH, et al. The patient’s guide to psoriasis treatment. part 3: biologic injectables. Dermatol Ther (Heidelb). 2016;6:325-331.

Aldredge LM, Young MS. Providing guidance for patients with moderate-to-severe psoriasis who are candidates for biologic therapy. J Dermatol Nurses Assoc. 2016;8:14-26.

National Psoriasis Foundation. Self-injections 101. https://www.psoriasis.org/about-psoriasis/treatments/biologics/self-injections-101. Accessed January 2, 2018.

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Myth: Patients Are Not Willing to Give Themselves Injections

Injectable biologics target specific parts of the immune system, making them popular treatment options for psoriasis patients, with ample research on their efficacy. Performing a self-injection can be daunting for patients trying a biologic for the first time, and clinicians should be aware of the dearth of patient education material. Although patients may be fearful of self-injections, especially the first few treatments, their worries can be assuaged with proper instruction and appropriate delivery method.

Abrouk et al sought to provide an online guide and video on biologic injections to increase the success of the therapy and compliance among patients. They created a printable guide that covers the supplies needed, procedure techniques, and plans for traveling with medications. Because pain is a common concern for patients, they suggest numbing the injection area with an ice pack first. They also offer tips on dealing with injection-site reactions such as redness or bruising.

Nurse practitioners and physician assistants can be used to give psoriasis patients more personalized attention regarding the fear of injections. They can explain the injection procedures and describe differences between administration techniques. Some patients may prefer using an autoinjector versus a prefilled syringe, which may impact the treatment administered. Taking photographs to show progress with therapy also may motivate patients to tolerate therapy.

The National Psoriasis Foundation provides the following tips to make it easier for patients to self-inject and reduce the chance of an injection-site reaction:

  • Pick an easy injection site, such as the top of the rights, abdomen, or back of the arms.
  • Rotate injection sites from right to left.
  • Numb the area.
  • Warm the pen up by taking it out of the refrigerator 1.5 hours before it is used.
  • Be patient and avoid moving the injection pen before the needle is finished administering the drug.

By giving psoriasis patients educational materials, you can empower them to control their disease with injectable biologics.

Expert Commentary

Most of my patients who use a biologic for the first time are undaunted by learning to inject themselves. I can think of just 1 of my ~300 biologic patients who has to come in every few weeks for their medicine to be injected by one of our nurses. Surprisingly, some patients (I'd estimate 5% of my biologic patients) actually prefer the syringe compared to the autoinjector, with some comments saying that the syringe is less painful and less abrupt. Needle phobia should not be a reason to not prescribe a biologic for a patient with severe psoriasis who needs it.

—Jashin J. Wu, MD (Los Angeles, California)

Myth: Patients Are Not Willing to Give Themselves Injections

Injectable biologics target specific parts of the immune system, making them popular treatment options for psoriasis patients, with ample research on their efficacy. Performing a self-injection can be daunting for patients trying a biologic for the first time, and clinicians should be aware of the dearth of patient education material. Although patients may be fearful of self-injections, especially the first few treatments, their worries can be assuaged with proper instruction and appropriate delivery method.

Abrouk et al sought to provide an online guide and video on biologic injections to increase the success of the therapy and compliance among patients. They created a printable guide that covers the supplies needed, procedure techniques, and plans for traveling with medications. Because pain is a common concern for patients, they suggest numbing the injection area with an ice pack first. They also offer tips on dealing with injection-site reactions such as redness or bruising.

Nurse practitioners and physician assistants can be used to give psoriasis patients more personalized attention regarding the fear of injections. They can explain the injection procedures and describe differences between administration techniques. Some patients may prefer using an autoinjector versus a prefilled syringe, which may impact the treatment administered. Taking photographs to show progress with therapy also may motivate patients to tolerate therapy.

The National Psoriasis Foundation provides the following tips to make it easier for patients to self-inject and reduce the chance of an injection-site reaction:

  • Pick an easy injection site, such as the top of the rights, abdomen, or back of the arms.
  • Rotate injection sites from right to left.
  • Numb the area.
  • Warm the pen up by taking it out of the refrigerator 1.5 hours before it is used.
  • Be patient and avoid moving the injection pen before the needle is finished administering the drug.

By giving psoriasis patients educational materials, you can empower them to control their disease with injectable biologics.

Expert Commentary

Most of my patients who use a biologic for the first time are undaunted by learning to inject themselves. I can think of just 1 of my ~300 biologic patients who has to come in every few weeks for their medicine to be injected by one of our nurses. Surprisingly, some patients (I'd estimate 5% of my biologic patients) actually prefer the syringe compared to the autoinjector, with some comments saying that the syringe is less painful and less abrupt. Needle phobia should not be a reason to not prescribe a biologic for a patient with severe psoriasis who needs it.

—Jashin J. Wu, MD (Los Angeles, California)

References

Abrouk M, Nakamura M, Zhu TH, et al. The patient’s guide to psoriasis treatment. part 3: biologic injectables. Dermatol Ther (Heidelb). 2016;6:325-331.

Aldredge LM, Young MS. Providing guidance for patients with moderate-to-severe psoriasis who are candidates for biologic therapy. J Dermatol Nurses Assoc. 2016;8:14-26.

National Psoriasis Foundation. Self-injections 101. https://www.psoriasis.org/about-psoriasis/treatments/biologics/self-injections-101. Accessed January 2, 2018.

References

Abrouk M, Nakamura M, Zhu TH, et al. The patient’s guide to psoriasis treatment. part 3: biologic injectables. Dermatol Ther (Heidelb). 2016;6:325-331.

Aldredge LM, Young MS. Providing guidance for patients with moderate-to-severe psoriasis who are candidates for biologic therapy. J Dermatol Nurses Assoc. 2016;8:14-26.

National Psoriasis Foundation. Self-injections 101. https://www.psoriasis.org/about-psoriasis/treatments/biologics/self-injections-101. Accessed January 2, 2018.

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Guselkumab crushes skin disease in psoriatic arthritis patients

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– The interleukin-23 inhibitor guselkumab generates the same impressive improvement in skin disease in psoriatic arthritis patients as has been seen in psoriasis without joint disease, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

However, psoriatic arthritis patients’ improvement in Dermatology Life Quality Index (DLQI) scores is less robust than in patients with psoriasis only, added Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center.

Bruce Jancin/Frontline Medical News
Dr. Alexa B. Kimball
She presented a secondary analysis of 1,829 patients with moderate to severe plaque psoriasis who participated in the pivotal phase 3, randomized, double-blind VOYAGE 1 and VOYAGE 2 trials, which helped guselkumab win Food and Drug Administration approval as Tremfya for treatment of psoriasis in July 2017. The purpose was to see how guselkumab stacked up in terms of efficacy and safety in the 335 participants with psoriatic arthritis versus the 1,494 without the rheumatologic disease.

The psoriatic arthritis group as a whole had more severe psoriasis, with a baseline mean PASI score of 24.3 and involvement of 32.7% of their body surface area as compared with a PASI score of 21.2 and 27.2% BSA in psoriasis patients without arthritis. A total of 28% of the psoriatic arthritis patients had previously been on other biologics and 77% had been on nonbiologic systemic agents, compared with 19% and 60% of the psoriasis patients, respectively. The psoriatic arthritis group had a mean 19.2-year history of psoriasis, 1.9 years longer than the psoriasis-only group.

Participants were randomized to 100 mg of guselkumab administered subcutaneously at weeks 0, 4, 12, and 20; placebo through week 12, followed by a switch to adalimumab (Humira); or adalimumab at 80 mg at week 0, then 40 mg at week 2 and 40 mg again every 2 weeks until week 23.

The key findings:

The PASI 90 response rate – that is, at least a 90% improvement in Psoriasis Area and Severity Index – in guselkumab-treated patients at week 16 was 72% in patients with psoriatic arthritis and 71% in those without. At week 24, the PASI 90 rate was 74% in guselkumab-treated patients with psoriatic arthritis and similar at 78% in those without. In contrast, the PASI 90 rate at week 24 in patients on adalimumab was significantly lower: 48% in the psoriatic arthritis group and 55% in those with psoriasis only. The PASI 90 rate in placebo-treated controls was single digit.

At week 24, 82% of psoriatic arthritis patients on guselkumab had clear or almost clear skin as reflected in an Investigator’s Global Assessment score of 0 or 1, as did 84% of psoriasis-only patients.

A DLQI score of 0 or 1, meaning the dermatologic disease had no impact on patient quality of life, was documented at week 16 in 46% of psoriatic arthritis patients and 55% of psoriasis-only patients, a trend that didn’t achieve statistical significance. However, by week 24 the difference became significant, with a DLQI of 0 or 1 in 48% of the psoriatic arthritis patients, compared with 62% of psoriasis-only patients.

VOYAGE 1 and 2 were dermatologic studies that didn’t measure changes in joint symptom scores or other psoriatic arthritis outcomes. Guselkumab as a potential treatment for psoriatic arthritis is under investigation in other studies.

The VOYAGE trials and this analysis were sponsored by Janssen. Dr. Kimball reported receiving research funding from and serving as a consultant to Janssen and numerous other pharmaceutical companies.

SOURCE: Kimball A et al. https://eadvgeneva2017.org/

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– The interleukin-23 inhibitor guselkumab generates the same impressive improvement in skin disease in psoriatic arthritis patients as has been seen in psoriasis without joint disease, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

However, psoriatic arthritis patients’ improvement in Dermatology Life Quality Index (DLQI) scores is less robust than in patients with psoriasis only, added Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center.

Bruce Jancin/Frontline Medical News
Dr. Alexa B. Kimball
She presented a secondary analysis of 1,829 patients with moderate to severe plaque psoriasis who participated in the pivotal phase 3, randomized, double-blind VOYAGE 1 and VOYAGE 2 trials, which helped guselkumab win Food and Drug Administration approval as Tremfya for treatment of psoriasis in July 2017. The purpose was to see how guselkumab stacked up in terms of efficacy and safety in the 335 participants with psoriatic arthritis versus the 1,494 without the rheumatologic disease.

The psoriatic arthritis group as a whole had more severe psoriasis, with a baseline mean PASI score of 24.3 and involvement of 32.7% of their body surface area as compared with a PASI score of 21.2 and 27.2% BSA in psoriasis patients without arthritis. A total of 28% of the psoriatic arthritis patients had previously been on other biologics and 77% had been on nonbiologic systemic agents, compared with 19% and 60% of the psoriasis patients, respectively. The psoriatic arthritis group had a mean 19.2-year history of psoriasis, 1.9 years longer than the psoriasis-only group.

Participants were randomized to 100 mg of guselkumab administered subcutaneously at weeks 0, 4, 12, and 20; placebo through week 12, followed by a switch to adalimumab (Humira); or adalimumab at 80 mg at week 0, then 40 mg at week 2 and 40 mg again every 2 weeks until week 23.

The key findings:

The PASI 90 response rate – that is, at least a 90% improvement in Psoriasis Area and Severity Index – in guselkumab-treated patients at week 16 was 72% in patients with psoriatic arthritis and 71% in those without. At week 24, the PASI 90 rate was 74% in guselkumab-treated patients with psoriatic arthritis and similar at 78% in those without. In contrast, the PASI 90 rate at week 24 in patients on adalimumab was significantly lower: 48% in the psoriatic arthritis group and 55% in those with psoriasis only. The PASI 90 rate in placebo-treated controls was single digit.

At week 24, 82% of psoriatic arthritis patients on guselkumab had clear or almost clear skin as reflected in an Investigator’s Global Assessment score of 0 or 1, as did 84% of psoriasis-only patients.

A DLQI score of 0 or 1, meaning the dermatologic disease had no impact on patient quality of life, was documented at week 16 in 46% of psoriatic arthritis patients and 55% of psoriasis-only patients, a trend that didn’t achieve statistical significance. However, by week 24 the difference became significant, with a DLQI of 0 or 1 in 48% of the psoriatic arthritis patients, compared with 62% of psoriasis-only patients.

VOYAGE 1 and 2 were dermatologic studies that didn’t measure changes in joint symptom scores or other psoriatic arthritis outcomes. Guselkumab as a potential treatment for psoriatic arthritis is under investigation in other studies.

The VOYAGE trials and this analysis were sponsored by Janssen. Dr. Kimball reported receiving research funding from and serving as a consultant to Janssen and numerous other pharmaceutical companies.

SOURCE: Kimball A et al. https://eadvgeneva2017.org/

 

– The interleukin-23 inhibitor guselkumab generates the same impressive improvement in skin disease in psoriatic arthritis patients as has been seen in psoriasis without joint disease, Alexa B. Kimball, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

However, psoriatic arthritis patients’ improvement in Dermatology Life Quality Index (DLQI) scores is less robust than in patients with psoriasis only, added Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, and CEO of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center.

Bruce Jancin/Frontline Medical News
Dr. Alexa B. Kimball
She presented a secondary analysis of 1,829 patients with moderate to severe plaque psoriasis who participated in the pivotal phase 3, randomized, double-blind VOYAGE 1 and VOYAGE 2 trials, which helped guselkumab win Food and Drug Administration approval as Tremfya for treatment of psoriasis in July 2017. The purpose was to see how guselkumab stacked up in terms of efficacy and safety in the 335 participants with psoriatic arthritis versus the 1,494 without the rheumatologic disease.

The psoriatic arthritis group as a whole had more severe psoriasis, with a baseline mean PASI score of 24.3 and involvement of 32.7% of their body surface area as compared with a PASI score of 21.2 and 27.2% BSA in psoriasis patients without arthritis. A total of 28% of the psoriatic arthritis patients had previously been on other biologics and 77% had been on nonbiologic systemic agents, compared with 19% and 60% of the psoriasis patients, respectively. The psoriatic arthritis group had a mean 19.2-year history of psoriasis, 1.9 years longer than the psoriasis-only group.

Participants were randomized to 100 mg of guselkumab administered subcutaneously at weeks 0, 4, 12, and 20; placebo through week 12, followed by a switch to adalimumab (Humira); or adalimumab at 80 mg at week 0, then 40 mg at week 2 and 40 mg again every 2 weeks until week 23.

The key findings:

The PASI 90 response rate – that is, at least a 90% improvement in Psoriasis Area and Severity Index – in guselkumab-treated patients at week 16 was 72% in patients with psoriatic arthritis and 71% in those without. At week 24, the PASI 90 rate was 74% in guselkumab-treated patients with psoriatic arthritis and similar at 78% in those without. In contrast, the PASI 90 rate at week 24 in patients on adalimumab was significantly lower: 48% in the psoriatic arthritis group and 55% in those with psoriasis only. The PASI 90 rate in placebo-treated controls was single digit.

At week 24, 82% of psoriatic arthritis patients on guselkumab had clear or almost clear skin as reflected in an Investigator’s Global Assessment score of 0 or 1, as did 84% of psoriasis-only patients.

A DLQI score of 0 or 1, meaning the dermatologic disease had no impact on patient quality of life, was documented at week 16 in 46% of psoriatic arthritis patients and 55% of psoriasis-only patients, a trend that didn’t achieve statistical significance. However, by week 24 the difference became significant, with a DLQI of 0 or 1 in 48% of the psoriatic arthritis patients, compared with 62% of psoriasis-only patients.

VOYAGE 1 and 2 were dermatologic studies that didn’t measure changes in joint symptom scores or other psoriatic arthritis outcomes. Guselkumab as a potential treatment for psoriatic arthritis is under investigation in other studies.

The VOYAGE trials and this analysis were sponsored by Janssen. Dr. Kimball reported receiving research funding from and serving as a consultant to Janssen and numerous other pharmaceutical companies.

SOURCE: Kimball A et al. https://eadvgeneva2017.org/

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Key clinical point: Guselkumab achieves consistent skin outcomes in psoriasis with and without arthritis.

Major finding: After 16 weeks on guselkumab, 72% of psoriatic arthritis patients and 71% with psoriasis-only had a PASI 90 response.

Study details: This was a comparison of skin and DLQI outcomes in 335 patients with psoriatic arthritis and 1,494 with psoriasis only who participated in two randomized, double-blind, phase 3 clinical trials.

Disclosures: Janssen sponsored the study. The presenter reported receiving research grants from and serving as a consultant to Janssen and numerous other pharmaceutical companies.

Source: Kimball A et al. https://eadvgeneva2017.org/.

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