Psoriasis

SEATTLE – The availability of biologics for treating psoriasis and psoriatic arthritis has exploded in recent years, with 11 biologics now approved by the Food and Drug Administration. Targets include four separate mechanisms: inhibition of tumor necrosis factor (TNF), interleukin (IL) 23, IL-12/23, and IL-17. The surfeit of treatment options can be a little overwhelming.

“It can be confusing. We have a lot of choices, but the good news is that most of our choices are excellent, and they treat both psoriasis and psoriatic arthritis. That’s very important because, when we think of our psoriasis patients, we need to think not only about their skin but also their joint involvement. Assessment of psoriatic arthritis will drive some of our therapeutic [decisions],” April Armstrong, MD, professor of dermatology at the University of Southern California, Los Angeles, said at the annual Coastal Dermatology Symposium.

In April, the American Academy of Dermatology came to the rescue with comprehensive guidelines. Aside from general advice, the guidelines “provide tips for monitoring as well as dose escalation, which will be very helpful in daily practice,” Dr. Armstrong said in an interview.

The best studied of the biologics with respect to psoriasis and psoriatic arthritis are the IL-17 inhibitors and TNF inhibitors, she said. While TNF inhibitors have traditionally been the treatment of choice for both conditions, “I think these days, people realize that IL-17 inhibitors can be just as good.”

A head-to-head study of the IL-17 inhibitor ixekizumab and the TNF inhibitor adalimumab, presented at the EULAR Congress, looked at a combined outcome of skin and joints and found ixekizumab to be superior, though the study design’s inclusion of a skin outcome may have favored ixekizumab (Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709).

A few other head-to-head studies have been performed, but properly ranking all 11 biologics would require dozens of clinical trials. At the American Academy of Dermatology meeting last March, Dr. Armstrong presented the results of a network meta-analysis of anti-TNF agents, anti-interleukin agents, anti–phosphodiesterase 4 agents, and fumaric acid esters (J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.06.488). That study, funded by AbbVie, compared the individual agents to a collective placebo group and concluded that anti-interleukin agents generate the highest level of PASI 90/100 response rate. Risankizumab, ixekizumab, brodalumab, and guselkumab, all IL inhibitors, achieved the best marks over the primary response period.

The AAD guidelines include recommendations for tests to be done upon initiation of a biologic, including a tuberculosis test, complete blood count, comprehensive metabolic panel, and tests for hepatitis B and C. TB testing should be performed annually during treatment.

The guidelines also include recommendations for dose escalation, which can provide leverage for getting coverage approved. “One can use those guidelines to show payers how dose escalation can be done, so that [physicians] can potentially get more access to medications for their patients,” Dr. Armstrong said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

The guideline also ranks the existing evidence supporting individual biologics for the treatment of psoriasis subtypes. For example, for the treatment of moderate to severe scalp psoriasis, etanercept and guselkumab have consistent and good-quality patient-oriented evidence supporting them; infliximab, adalimumab, secukinumab, and ixekizumab are recommended based on inconsistent or limited quality patient-oriented evidence; and ustekinumab is supported only by consensus opinion, case studies, or disease-oriented evidence. The guidelines provide similar categorization of biologics for the treatment of moderate to severe plaque type palmoplantar psoriasis, moderate to severe psoriasis affecting the nails, adults with pustular or erythrodermic psoriasis, and adults with psoriatic arthritis.

Dr. Armstrong is a research investigator and/or advisor to AbbVie, Janssen, Lily, LEO Pharma, Novartis, UCB, Ortho Dermatologics, Dermera, Regeneron, BMS, Dermavant, and KHK. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – The availability of biologics for treating psoriasis and psoriatic arthritis has exploded in recent years, with 11 biologics now approved by the Food and Drug Administration. Targets include four separate mechanisms: inhibition of tumor necrosis factor (TNF), interleukin (IL) 23, IL-12/23, and IL-17. The surfeit of treatment options can be a little overwhelming.

“It can be confusing. We have a lot of choices, but the good news is that most of our choices are excellent, and they treat both psoriasis and psoriatic arthritis. That’s very important because, when we think of our psoriasis patients, we need to think not only about their skin but also their joint involvement. Assessment of psoriatic arthritis will drive some of our therapeutic [decisions],” April Armstrong, MD, professor of dermatology at the University of Southern California, Los Angeles, said at the annual Coastal Dermatology Symposium.

In April, the American Academy of Dermatology came to the rescue with comprehensive guidelines. Aside from general advice, the guidelines “provide tips for monitoring as well as dose escalation, which will be very helpful in daily practice,” Dr. Armstrong said in an interview.

The best studied of the biologics with respect to psoriasis and psoriatic arthritis are the IL-17 inhibitors and TNF inhibitors, she said. While TNF inhibitors have traditionally been the treatment of choice for both conditions, “I think these days, people realize that IL-17 inhibitors can be just as good.”

A head-to-head study of the IL-17 inhibitor ixekizumab and the TNF inhibitor adalimumab, presented at the EULAR Congress, looked at a combined outcome of skin and joints and found ixekizumab to be superior, though the study design’s inclusion of a skin outcome may have favored ixekizumab (Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709).

A few other head-to-head studies have been performed, but properly ranking all 11 biologics would require dozens of clinical trials. At the American Academy of Dermatology meeting last March, Dr. Armstrong presented the results of a network meta-analysis of anti-TNF agents, anti-interleukin agents, anti–phosphodiesterase 4 agents, and fumaric acid esters (J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.06.488). That study, funded by AbbVie, compared the individual agents to a collective placebo group and concluded that anti-interleukin agents generate the highest level of PASI 90/100 response rate. Risankizumab, ixekizumab, brodalumab, and guselkumab, all IL inhibitors, achieved the best marks over the primary response period.

The AAD guidelines include recommendations for tests to be done upon initiation of a biologic, including a tuberculosis test, complete blood count, comprehensive metabolic panel, and tests for hepatitis B and C. TB testing should be performed annually during treatment.

The guidelines also include recommendations for dose escalation, which can provide leverage for getting coverage approved. “One can use those guidelines to show payers how dose escalation can be done, so that [physicians] can potentially get more access to medications for their patients,” Dr. Armstrong said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

The guideline also ranks the existing evidence supporting individual biologics for the treatment of psoriasis subtypes. For example, for the treatment of moderate to severe scalp psoriasis, etanercept and guselkumab have consistent and good-quality patient-oriented evidence supporting them; infliximab, adalimumab, secukinumab, and ixekizumab are recommended based on inconsistent or limited quality patient-oriented evidence; and ustekinumab is supported only by consensus opinion, case studies, or disease-oriented evidence. The guidelines provide similar categorization of biologics for the treatment of moderate to severe plaque type palmoplantar psoriasis, moderate to severe psoriasis affecting the nails, adults with pustular or erythrodermic psoriasis, and adults with psoriatic arthritis.

Dr. Armstrong is a research investigator and/or advisor to AbbVie, Janssen, Lily, LEO Pharma, Novartis, UCB, Ortho Dermatologics, Dermera, Regeneron, BMS, Dermavant, and KHK. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – The availability of biologics for treating psoriasis and psoriatic arthritis has exploded in recent years, with 11 biologics now approved by the Food and Drug Administration. Targets include four separate mechanisms: inhibition of tumor necrosis factor (TNF), interleukin (IL) 23, IL-12/23, and IL-17. The surfeit of treatment options can be a little overwhelming.

“It can be confusing. We have a lot of choices, but the good news is that most of our choices are excellent, and they treat both psoriasis and psoriatic arthritis. That’s very important because, when we think of our psoriasis patients, we need to think not only about their skin but also their joint involvement. Assessment of psoriatic arthritis will drive some of our therapeutic [decisions],” April Armstrong, MD, professor of dermatology at the University of Southern California, Los Angeles, said at the annual Coastal Dermatology Symposium.

In April, the American Academy of Dermatology came to the rescue with comprehensive guidelines. Aside from general advice, the guidelines “provide tips for monitoring as well as dose escalation, which will be very helpful in daily practice,” Dr. Armstrong said in an interview.

The best studied of the biologics with respect to psoriasis and psoriatic arthritis are the IL-17 inhibitors and TNF inhibitors, she said. While TNF inhibitors have traditionally been the treatment of choice for both conditions, “I think these days, people realize that IL-17 inhibitors can be just as good.”

A head-to-head study of the IL-17 inhibitor ixekizumab and the TNF inhibitor adalimumab, presented at the EULAR Congress, looked at a combined outcome of skin and joints and found ixekizumab to be superior, though the study design’s inclusion of a skin outcome may have favored ixekizumab (Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709).

A few other head-to-head studies have been performed, but properly ranking all 11 biologics would require dozens of clinical trials. At the American Academy of Dermatology meeting last March, Dr. Armstrong presented the results of a network meta-analysis of anti-TNF agents, anti-interleukin agents, anti–phosphodiesterase 4 agents, and fumaric acid esters (J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.06.488). That study, funded by AbbVie, compared the individual agents to a collective placebo group and concluded that anti-interleukin agents generate the highest level of PASI 90/100 response rate. Risankizumab, ixekizumab, brodalumab, and guselkumab, all IL inhibitors, achieved the best marks over the primary response period.

The AAD guidelines include recommendations for tests to be done upon initiation of a biologic, including a tuberculosis test, complete blood count, comprehensive metabolic panel, and tests for hepatitis B and C. TB testing should be performed annually during treatment.

The guidelines also include recommendations for dose escalation, which can provide leverage for getting coverage approved. “One can use those guidelines to show payers how dose escalation can be done, so that [physicians] can potentially get more access to medications for their patients,” Dr. Armstrong said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

The guideline also ranks the existing evidence supporting individual biologics for the treatment of psoriasis subtypes. For example, for the treatment of moderate to severe scalp psoriasis, etanercept and guselkumab have consistent and good-quality patient-oriented evidence supporting them; infliximab, adalimumab, secukinumab, and ixekizumab are recommended based on inconsistent or limited quality patient-oriented evidence; and ustekinumab is supported only by consensus opinion, case studies, or disease-oriented evidence. The guidelines provide similar categorization of biologics for the treatment of moderate to severe plaque type palmoplantar psoriasis, moderate to severe psoriasis affecting the nails, adults with pustular or erythrodermic psoriasis, and adults with psoriatic arthritis.

Dr. Armstrong is a research investigator and/or advisor to AbbVie, Janssen, Lily, LEO Pharma, Novartis, UCB, Ortho Dermatologics, Dermera, Regeneron, BMS, Dermavant, and KHK. This publication and Global Academy for Medical Education are owned by the same parent company.

There are 4 variants of psoriasis: plaque, guttate, pustular, and erythroderma (in order of prevalence).² Guttate psoriasis is characterized by small, 2- to 10-mm, raindroplike lesions on the skin.¹ It accounts for approximately 2% of total psoriasis cases and is commonly triggered by group A streptococcal pharyngitis or tonsillitis.^3,4

Hand-foot-and-mouth disease (HFMD) is an illness most commonly caused by a coxsackievirus A infection but also can be caused by other enteroviruses.^5,6 Coxsackievirus is a serotype of the Enterovirus species within the Picornaviridae family.⁷ Hand-foot-and-mouth disease is characterized by a brief fever and vesicular rashes on the palms, soles, or buttocks, as well as oropharyngeal ulcers.⁸ Typically, the rash is benign and short-lived.⁹ In rare cases, neurologic complications develop. There have been no reported cases of guttate psoriasis following a coxsackievirus A infection.

The involvement of coxsackievirus B in the etiopathogenesis of psoriasis has been previously reported.¹⁰ We report the case of guttate psoriasis following presumed coxsackievirus A HFMD.

Case Report

A 56-year-old woman presented with a vesicular rash on the hands, feet, and lips. The patient reported having a sore throat that started around the same time that the rash developed. The severity of the sore throat was rated as moderate. No fever was reported. One day prior, the patient’s primary care physician prescribed a tapered course of prednisone for the rash. The patient reported a medical history of herpes zoster virus, sunburn, and genital herpes. She was taking clonazepam and had a known allergy to penicillin.

Physical examination revealed erythematous vesicular and papular lesions on the extensor surfaces of the hands and feet. Vesicles also were noted on the vermilion border of the lip. Examination of the patient’s mouth showed blisters and shallow ulcerations in the oral cavity. A clinical diagnosis of coxsackievirus A HFMD was made, and the treatment plan included triamcinolone acetonide ointment 0.025% applied twice daily for 2 weeks and oral valacyclovir hydrochloride 1 g taken 3 times daily for 7 days. A topical emollient also was recommended for the lips when necessary. The lesions all resolved within a 2-week period with no sequela.

The patient returned 1 month later, citing newer red abdominal skin lesions. Fever was denied. She reported that both prescribed treatments had not been helping for the newer lesions. She noticed similar lesions on the groin and brought them to the attention of her gynecologist. Physical examination revealed salmon pink papules and plaques with silvery scaling involving the abdomen, bilateral upper extremities and ears, and scalp. The patient was then clinically diagnosed with guttate psoriasis. A shave biopsy of a representative lesion on the abdomen was performed. The treatment plan included betamethasone dipropionate cream 0.05% applied twice daily for 2 weeks, clobetasol propionate solution 0.05% applied twice daily for 14 days (for the scalp), and hydrocortisone valerate cream 0.2% applied twice daily for 14 days (for the groin).

The skin biopsy shown in the Figure was received in 10% buffered formalin, measuring 5×4×1 mm of skin. Sections showed an acanthotic epidermis with foci of spongiosis and hypergranulosis covered by mounds of parakeratosis infiltrated by neutrophils. Superficial perivascular and interstitial lymphocytic inflammation was present. Tortuous blood vessels within the papillary dermis also were present. Results showed psoriasiform dermatitis with mild spongiosis. Periodic acid–Schiff stain did not reveal any fungal organisms. These findings were consistent with a diagnosis of guttate psoriasis.

Comment

Enterovirus-derived HFMD likely is caused by coxsackie-virus A. Current evidence supports the theory that guttate psoriasis can be environmentally triggered in genetically susceptible individuals, often but not exclusively by a streptococcal infection. The causative agent elicits a T-cell–mediated reaction leading to increased type 1 helper T cells, IFN-γ, and IL-2 cytokine levels. HLA-Cw^∗0602–positive patients are considered genetically susceptible and more likely to develop guttate psoriasis following an environmental trigger. Based on the coincidence in timing of both diagnoses, this reported case of guttate psoriasis may have been triggered by a coxsackievirus A infection.

There are 4 variants of psoriasis: plaque, guttate, pustular, and erythroderma (in order of prevalence).² Guttate psoriasis is characterized by small, 2- to 10-mm, raindroplike lesions on the skin.¹ It accounts for approximately 2% of total psoriasis cases and is commonly triggered by group A streptococcal pharyngitis or tonsillitis.^3,4

Hand-foot-and-mouth disease (HFMD) is an illness most commonly caused by a coxsackievirus A infection but also can be caused by other enteroviruses.^5,6 Coxsackievirus is a serotype of the Enterovirus species within the Picornaviridae family.⁷ Hand-foot-and-mouth disease is characterized by a brief fever and vesicular rashes on the palms, soles, or buttocks, as well as oropharyngeal ulcers.⁸ Typically, the rash is benign and short-lived.⁹ In rare cases, neurologic complications develop. There have been no reported cases of guttate psoriasis following a coxsackievirus A infection.

The involvement of coxsackievirus B in the etiopathogenesis of psoriasis has been previously reported.¹⁰ We report the case of guttate psoriasis following presumed coxsackievirus A HFMD.

Case Report

A 56-year-old woman presented with a vesicular rash on the hands, feet, and lips. The patient reported having a sore throat that started around the same time that the rash developed. The severity of the sore throat was rated as moderate. No fever was reported. One day prior, the patient’s primary care physician prescribed a tapered course of prednisone for the rash. The patient reported a medical history of herpes zoster virus, sunburn, and genital herpes. She was taking clonazepam and had a known allergy to penicillin.

Physical examination revealed erythematous vesicular and papular lesions on the extensor surfaces of the hands and feet. Vesicles also were noted on the vermilion border of the lip. Examination of the patient’s mouth showed blisters and shallow ulcerations in the oral cavity. A clinical diagnosis of coxsackievirus A HFMD was made, and the treatment plan included triamcinolone acetonide ointment 0.025% applied twice daily for 2 weeks and oral valacyclovir hydrochloride 1 g taken 3 times daily for 7 days. A topical emollient also was recommended for the lips when necessary. The lesions all resolved within a 2-week period with no sequela.

The patient returned 1 month later, citing newer red abdominal skin lesions. Fever was denied. She reported that both prescribed treatments had not been helping for the newer lesions. She noticed similar lesions on the groin and brought them to the attention of her gynecologist. Physical examination revealed salmon pink papules and plaques with silvery scaling involving the abdomen, bilateral upper extremities and ears, and scalp. The patient was then clinically diagnosed with guttate psoriasis. A shave biopsy of a representative lesion on the abdomen was performed. The treatment plan included betamethasone dipropionate cream 0.05% applied twice daily for 2 weeks, clobetasol propionate solution 0.05% applied twice daily for 14 days (for the scalp), and hydrocortisone valerate cream 0.2% applied twice daily for 14 days (for the groin).

The skin biopsy shown in the Figure was received in 10% buffered formalin, measuring 5×4×1 mm of skin. Sections showed an acanthotic epidermis with foci of spongiosis and hypergranulosis covered by mounds of parakeratosis infiltrated by neutrophils. Superficial perivascular and interstitial lymphocytic inflammation was present. Tortuous blood vessels within the papillary dermis also were present. Results showed psoriasiform dermatitis with mild spongiosis. Periodic acid–Schiff stain did not reveal any fungal organisms. These findings were consistent with a diagnosis of guttate psoriasis.

Comment

Enterovirus-derived HFMD likely is caused by coxsackie-virus A. Current evidence supports the theory that guttate psoriasis can be environmentally triggered in genetically susceptible individuals, often but not exclusively by a streptococcal infection. The causative agent elicits a T-cell–mediated reaction leading to increased type 1 helper T cells, IFN-γ, and IL-2 cytokine levels. HLA-Cw^∗0602–positive patients are considered genetically susceptible and more likely to develop guttate psoriasis following an environmental trigger. Based on the coincidence in timing of both diagnoses, this reported case of guttate psoriasis may have been triggered by a coxsackievirus A infection.

There are 4 variants of psoriasis: plaque, guttate, pustular, and erythroderma (in order of prevalence).² Guttate psoriasis is characterized by small, 2- to 10-mm, raindroplike lesions on the skin.¹ It accounts for approximately 2% of total psoriasis cases and is commonly triggered by group A streptococcal pharyngitis or tonsillitis.^3,4

Hand-foot-and-mouth disease (HFMD) is an illness most commonly caused by a coxsackievirus A infection but also can be caused by other enteroviruses.^5,6 Coxsackievirus is a serotype of the Enterovirus species within the Picornaviridae family.⁷ Hand-foot-and-mouth disease is characterized by a brief fever and vesicular rashes on the palms, soles, or buttocks, as well as oropharyngeal ulcers.⁸ Typically, the rash is benign and short-lived.⁹ In rare cases, neurologic complications develop. There have been no reported cases of guttate psoriasis following a coxsackievirus A infection.

The involvement of coxsackievirus B in the etiopathogenesis of psoriasis has been previously reported.¹⁰ We report the case of guttate psoriasis following presumed coxsackievirus A HFMD.

Case Report

A 56-year-old woman presented with a vesicular rash on the hands, feet, and lips. The patient reported having a sore throat that started around the same time that the rash developed. The severity of the sore throat was rated as moderate. No fever was reported. One day prior, the patient’s primary care physician prescribed a tapered course of prednisone for the rash. The patient reported a medical history of herpes zoster virus, sunburn, and genital herpes. She was taking clonazepam and had a known allergy to penicillin.

Physical examination revealed erythematous vesicular and papular lesions on the extensor surfaces of the hands and feet. Vesicles also were noted on the vermilion border of the lip. Examination of the patient’s mouth showed blisters and shallow ulcerations in the oral cavity. A clinical diagnosis of coxsackievirus A HFMD was made, and the treatment plan included triamcinolone acetonide ointment 0.025% applied twice daily for 2 weeks and oral valacyclovir hydrochloride 1 g taken 3 times daily for 7 days. A topical emollient also was recommended for the lips when necessary. The lesions all resolved within a 2-week period with no sequela.

The patient returned 1 month later, citing newer red abdominal skin lesions. Fever was denied. She reported that both prescribed treatments had not been helping for the newer lesions. She noticed similar lesions on the groin and brought them to the attention of her gynecologist. Physical examination revealed salmon pink papules and plaques with silvery scaling involving the abdomen, bilateral upper extremities and ears, and scalp. The patient was then clinically diagnosed with guttate psoriasis. A shave biopsy of a representative lesion on the abdomen was performed. The treatment plan included betamethasone dipropionate cream 0.05% applied twice daily for 2 weeks, clobetasol propionate solution 0.05% applied twice daily for 14 days (for the scalp), and hydrocortisone valerate cream 0.2% applied twice daily for 14 days (for the groin).

The skin biopsy shown in the Figure was received in 10% buffered formalin, measuring 5×4×1 mm of skin. Sections showed an acanthotic epidermis with foci of spongiosis and hypergranulosis covered by mounds of parakeratosis infiltrated by neutrophils. Superficial perivascular and interstitial lymphocytic inflammation was present. Tortuous blood vessels within the papillary dermis also were present. Results showed psoriasiform dermatitis with mild spongiosis. Periodic acid–Schiff stain did not reveal any fungal organisms. These findings were consistent with a diagnosis of guttate psoriasis.

Comment

Enterovirus-derived HFMD likely is caused by coxsackie-virus A. Current evidence supports the theory that guttate psoriasis can be environmentally triggered in genetically susceptible individuals, often but not exclusively by a streptococcal infection. The causative agent elicits a T-cell–mediated reaction leading to increased type 1 helper T cells, IFN-γ, and IL-2 cytokine levels. HLA-Cw^∗0602–positive patients are considered genetically susceptible and more likely to develop guttate psoriasis following an environmental trigger. Based on the coincidence in timing of both diagnoses, this reported case of guttate psoriasis may have been triggered by a coxsackievirus A infection.

Psychological and Sexual Consequences of Psoriasis Vulgaris on Patients and Their Partners.

Alariny AF, Farid CI, Elweshahi HM, Abbood SS. J Sex Med. 2019 Sep 18.

In a comparative cross-sectional study that aimed to evaluate the psychopathological and sexual aspects of psoriasis vulgaris in patients and their partners, the sample included 220 psoriasis vulgaris patients (110 males and 110 females), their consenting partners, and 220 age- and sex-matched healthy controls. The main outcome measures were frequency of depression, anxiety, low self-esteem, and sexual dysfunction in psoriasis vulgaris patients, partners, and controls; the domains of sexual function affected in the studied groups; and the etiology of erectile dysfunction in affected psoriatic males.

Ceramide- and Keratolytic-containing Body Cleanser and Cream Application in Patients with Psoriasis: Outcomes from a Consumer Usage Study.

Del Rosso JQ. J Clin Aesthet Dermatol. 2019 Jul;12(7):18-21

Ceramides are epidermal lipids that play an essential role in stratum corneum function, including maintaining physiologic permeability barrier properties. The role of ceramides in the maintenance and repair of epidermal barrier function is believed to be valuable in the treatment of psoriasis. Normalization of corneocyte desquamation and the incorporation of agents that promote desquamation to reduce hyperkeratosis are also regarded as key factors in psoriasis management. Based on results reported by the study patients, the evaluated ceramide/keratolytic-containing cream and cleanser both yielded a high level of patient acceptance regarding improvement in skin characteristics in patients with psoriasis, including when used as a combination adjunctive regimen.

Split thickness skin graft in active psoriasis in patient with clear cell variant squamous cell carcinoma.

Scupham L, Ingle A. BMJ Case Rep. 2019 Sep 16;12(9).

The case report discusses split thickness skin grafting in a patient with active psoriasis. This also reports a case of a rare variant of squamous cell carcinoma.

Epicardial Adipose Tissue Inflammation Can Cause the Distinctive Pattern of Cardiovascular Disorders Seen in Psoriasis.

Packer M. Am J Med. 2019 Sep 11.

Psoriasis is a systemic inflammatory disorder that can target adipose tissue; the resulting adipocyte dysfunction is manifest clinically as the metabolic syndrome, which is present in ≈20-40% of patients. Epicardial adipose tissue inflammation is likely responsible for a distinctive pattern of cardiovascular disorders, consisting of: accelerated coronary atherosclerosis leading to myocardial infarction, atrial myopathy leading to atrial fibrillation and thromboembolic stroke, and ventricular myopathy leading to heart failure with a preserved ejection fraction. If cardiovascular inflammation drives these risks, then treatments that focus on blood pressure, lipids and glucose will not ameliorate the burden of cardiovascular disease in patients with psoriasis, especially in those who are young and have severe inflammation. Instead, interventions that alleviate systemic and adipose tissue inflammation may not only minimize the risks of atrial fibrillation and heart failure, but may also have favorable effects on the severity of psoriasis. Viewed from this perspective, the known link between psoriasis and cardiovascular disease is not related to the influence of the individual diagnostic components of the metabolic syndrome.

Musculoskeletal ultrasound can improve referrals from dermatology to rheumatology for patients with psoriasis.

Solmaz D, Bakirci S, Al Onazi A, Al Osaimi N, Fahim S, Aydin SZ. Br J Dermatol. 2019 Sep 10.

Psoriasis affects 1-3% of the population and up to 1/3 of psoriasis patients have underlying psoriatic arthritis (PsA). Non-specific musculoskeletal complaints are even higher, being around 50%. Detecting early signs of PsA and early treatments are crucial to improve the outcomes to prevent progressive, damaging arthritis. Due to the high frequency of non-specific pain in psoriasis, it is not possible for every psoriasis patient with joint pain to be assessed by a rheumato

Psychological and Sexual Consequences of Psoriasis Vulgaris on Patients and Their Partners.

Alariny AF, Farid CI, Elweshahi HM, Abbood SS. J Sex Med. 2019 Sep 18.

In a comparative cross-sectional study that aimed to evaluate the psychopathological and sexual aspects of psoriasis vulgaris in patients and their partners, the sample included 220 psoriasis vulgaris patients (110 males and 110 females), their consenting partners, and 220 age- and sex-matched healthy controls. The main outcome measures were frequency of depression, anxiety, low self-esteem, and sexual dysfunction in psoriasis vulgaris patients, partners, and controls; the domains of sexual function affected in the studied groups; and the etiology of erectile dysfunction in affected psoriatic males.

Ceramide- and Keratolytic-containing Body Cleanser and Cream Application in Patients with Psoriasis: Outcomes from a Consumer Usage Study.

Del Rosso JQ. J Clin Aesthet Dermatol. 2019 Jul;12(7):18-21

Ceramides are epidermal lipids that play an essential role in stratum corneum function, including maintaining physiologic permeability barrier properties. The role of ceramides in the maintenance and repair of epidermal barrier function is believed to be valuable in the treatment of psoriasis. Normalization of corneocyte desquamation and the incorporation of agents that promote desquamation to reduce hyperkeratosis are also regarded as key factors in psoriasis management. Based on results reported by the study patients, the evaluated ceramide/keratolytic-containing cream and cleanser both yielded a high level of patient acceptance regarding improvement in skin characteristics in patients with psoriasis, including when used as a combination adjunctive regimen.

Split thickness skin graft in active psoriasis in patient with clear cell variant squamous cell carcinoma.

Scupham L, Ingle A. BMJ Case Rep. 2019 Sep 16;12(9).

The case report discusses split thickness skin grafting in a patient with active psoriasis. This also reports a case of a rare variant of squamous cell carcinoma.

Epicardial Adipose Tissue Inflammation Can Cause the Distinctive Pattern of Cardiovascular Disorders Seen in Psoriasis.

Packer M. Am J Med. 2019 Sep 11.

Psoriasis is a systemic inflammatory disorder that can target adipose tissue; the resulting adipocyte dysfunction is manifest clinically as the metabolic syndrome, which is present in ≈20-40% of patients. Epicardial adipose tissue inflammation is likely responsible for a distinctive pattern of cardiovascular disorders, consisting of: accelerated coronary atherosclerosis leading to myocardial infarction, atrial myopathy leading to atrial fibrillation and thromboembolic stroke, and ventricular myopathy leading to heart failure with a preserved ejection fraction. If cardiovascular inflammation drives these risks, then treatments that focus on blood pressure, lipids and glucose will not ameliorate the burden of cardiovascular disease in patients with psoriasis, especially in those who are young and have severe inflammation. Instead, interventions that alleviate systemic and adipose tissue inflammation may not only minimize the risks of atrial fibrillation and heart failure, but may also have favorable effects on the severity of psoriasis. Viewed from this perspective, the known link between psoriasis and cardiovascular disease is not related to the influence of the individual diagnostic components of the metabolic syndrome.

Musculoskeletal ultrasound can improve referrals from dermatology to rheumatology for patients with psoriasis.

Solmaz D, Bakirci S, Al Onazi A, Al Osaimi N, Fahim S, Aydin SZ. Br J Dermatol. 2019 Sep 10.

Psoriasis affects 1-3% of the population and up to 1/3 of psoriasis patients have underlying psoriatic arthritis (PsA). Non-specific musculoskeletal complaints are even higher, being around 50%. Detecting early signs of PsA and early treatments are crucial to improve the outcomes to prevent progressive, damaging arthritis. Due to the high frequency of non-specific pain in psoriasis, it is not possible for every psoriasis patient with joint pain to be assessed by a rheumato

Psychological and Sexual Consequences of Psoriasis Vulgaris on Patients and Their Partners.

Alariny AF, Farid CI, Elweshahi HM, Abbood SS. J Sex Med. 2019 Sep 18.

In a comparative cross-sectional study that aimed to evaluate the psychopathological and sexual aspects of psoriasis vulgaris in patients and their partners, the sample included 220 psoriasis vulgaris patients (110 males and 110 females), their consenting partners, and 220 age- and sex-matched healthy controls. The main outcome measures were frequency of depression, anxiety, low self-esteem, and sexual dysfunction in psoriasis vulgaris patients, partners, and controls; the domains of sexual function affected in the studied groups; and the etiology of erectile dysfunction in affected psoriatic males.

Ceramide- and Keratolytic-containing Body Cleanser and Cream Application in Patients with Psoriasis: Outcomes from a Consumer Usage Study.

Del Rosso JQ. J Clin Aesthet Dermatol. 2019 Jul;12(7):18-21

Ceramides are epidermal lipids that play an essential role in stratum corneum function, including maintaining physiologic permeability barrier properties. The role of ceramides in the maintenance and repair of epidermal barrier function is believed to be valuable in the treatment of psoriasis. Normalization of corneocyte desquamation and the incorporation of agents that promote desquamation to reduce hyperkeratosis are also regarded as key factors in psoriasis management. Based on results reported by the study patients, the evaluated ceramide/keratolytic-containing cream and cleanser both yielded a high level of patient acceptance regarding improvement in skin characteristics in patients with psoriasis, including when used as a combination adjunctive regimen.

Split thickness skin graft in active psoriasis in patient with clear cell variant squamous cell carcinoma.

Scupham L, Ingle A. BMJ Case Rep. 2019 Sep 16;12(9).

The case report discusses split thickness skin grafting in a patient with active psoriasis. This also reports a case of a rare variant of squamous cell carcinoma.

Epicardial Adipose Tissue Inflammation Can Cause the Distinctive Pattern of Cardiovascular Disorders Seen in Psoriasis.

Packer M. Am J Med. 2019 Sep 11.

Psoriasis is a systemic inflammatory disorder that can target adipose tissue; the resulting adipocyte dysfunction is manifest clinically as the metabolic syndrome, which is present in ≈20-40% of patients. Epicardial adipose tissue inflammation is likely responsible for a distinctive pattern of cardiovascular disorders, consisting of: accelerated coronary atherosclerosis leading to myocardial infarction, atrial myopathy leading to atrial fibrillation and thromboembolic stroke, and ventricular myopathy leading to heart failure with a preserved ejection fraction. If cardiovascular inflammation drives these risks, then treatments that focus on blood pressure, lipids and glucose will not ameliorate the burden of cardiovascular disease in patients with psoriasis, especially in those who are young and have severe inflammation. Instead, interventions that alleviate systemic and adipose tissue inflammation may not only minimize the risks of atrial fibrillation and heart failure, but may also have favorable effects on the severity of psoriasis. Viewed from this perspective, the known link between psoriasis and cardiovascular disease is not related to the influence of the individual diagnostic components of the metabolic syndrome.

Musculoskeletal ultrasound can improve referrals from dermatology to rheumatology for patients with psoriasis.

Solmaz D, Bakirci S, Al Onazi A, Al Osaimi N, Fahim S, Aydin SZ. Br J Dermatol. 2019 Sep 10.

Psoriasis affects 1-3% of the population and up to 1/3 of psoriasis patients have underlying psoriatic arthritis (PsA). Non-specific musculoskeletal complaints are even higher, being around 50%. Detecting early signs of PsA and early treatments are crucial to improve the outcomes to prevent progressive, damaging arthritis. Due to the high frequency of non-specific pain in psoriasis, it is not possible for every psoriasis patient with joint pain to be assessed by a rheumato

The expanded use of targeted anticancer agents such as sorafenib has revealed a growing spectrum of adverse cutaneous eruptions. We describe 3 patients with sorafenib-induced psoriasiform dermatitis and review the literature of only 10 other similar reported cases based on a search of PubMed, Web of Science, and American Society of Clinical Oncology abstracts using the terms psoriasis or psoriasiform dermatitis and sorafenib.^1-10 We seek to increase awareness of this particular drug eruption in response to sorafenib and to describe potential effective treatment options, especially when sorafenib cannot be discontinued.

Case Reports

Patient 1
A 68-year-old man with chronic hepatitis B infection and hepatocellular carcinoma (HCC) was started on sorafenib 400 mg daily. After 2 months of treatment, he developed painful hyperkeratotic lesions on the bilateral palms and soles with formation of calluses and superficial blisters on an erythematous base that was consistent with hand-foot skin reaction (HFSR). He also had numerous erythematous thin papules and plaques with adherent white scale and yellow crust on the bilateral thighs, lower legs, forearms, dorsal hands, abdomen, back, and buttocks (Figure 1). He had no personal or family history of psoriasis, and blood tests were unremarkable. Histologic analysis of punch biopsies from the buttocks and right leg revealed focal parakeratosis with neutrophils and serous crust, acanthosis, mild spongiosis, and lymphocytes at the dermoepidermal junction and surrounding dermal vessels, consistent with psoriasiform dermatitis (Figure 2). Sorafenib was discontinued and the eruption began to resolve within a week. A lower dose of sorafenib (200 mg daily) was attempted and the psoriasiform eruption recurred.

Patient 2
An 82-year-old man with chronic hepatitis B infection and HCC with lung metastasis was treated with sorafenib 400 mg daily. One week after treatment, he developed painful, thick, erythematous lesions on acral surfaces, consistent with HFSR. The sorafenib dose was decreased to 200 mg daily and HFSR resolved. Four months later, he developed well-demarcated, erythematous, scaly plaques with peripheral pustules on the right thigh (Figure 3) and right shin. He had no personal or family history of psoriasis, and blood tests were unremarkable. Samples from the pustules were taken for bacterial culture and fungal stain, but both were negative. Histologic analysis of a punch biopsy from the right thigh revealed necrotic parakeratosis, spongiform pustules, mild acanthosis, and a perivascular lymphocytic infiltrate with many neutrophils in the dermis. These findings suggested a diagnosis of pustular psoriasis, pustular drug eruption, or acute generalized exanthematous pustulosis. Treatment was initiated with mometasone cream. The patient subsequently developed hemoptysis and ascites from sorafenib. Sorafenib was discontinued and his skin eruption gradually resolved.

Comment

Sorafenib is an oral tyrosine kinase inhibitor that blocks tumor cell proliferation and angiogenesis due to its activity against vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, stem cell growth factor receptor, and rapidly accelerated fibrosarcoma kinases.¹¹ It is primarily used for the treatment of solid tumors, such as advanced renal cell carcinoma, unresectable HCC, and thyroid carcinoma, and more recently has been expanded for treatment of AML due to potential inhibition of FMS-like tyrosine kinase 3 receptor. Although dermatologic toxicity is a common adverse event during treatment with sorafenib,¹¹ reports of psoriasiform drug eruptions are rare.

Review of Cases
Based on our literature search, there are 10 previously reported cases of psoriasiform drug eruption secondary to sorafenib. Of the 13 total cases (including the 3 patients in this report), 7 patients had a history of psoriasis; most were middle-aged men; and the treatment with sorafenib was for solid tumors, primarily HCC with the exception of patient 3 from the current report who was treated for AML (Table). In all cases, the dose of sorafenib ranged from 200 to 800 mg daily. In 5 cases, HFSR preceded (as with patient 2 in the current report) or presented concurrently (as with patient 1 in the current report) with the onset of psoriasiform rash.^1,3,5

Vascular endothelial growth factor is overexpressed on psoriatic keratinocytes, contributes to epidermal hyperplasia, and induces angiogenesis in the dermis.¹² The development of psoriasiform eruptions in patients treated with sorafenib seems paradoxical, as this drug has been considered as potential therapy for psoriasis due to its ability to block VEGF receptor signaling. Indeed, an improvement of psoriasis has been reported in 1 case of a patient treated with sorafenib¹³ and in multiple patients with psoriasis treated with other VEGF antagonists (eg, bevacizumab).¹⁴ The underlying mechanisms by which sorafenib induced or exacerbated psoriasis are not entirely clear. Palmoplantar hyperkeratosis, keratosis pilaris–like eruption, multiple cysts, eruptive keratoacanthomas, and squamous cell carcinoma have been described in patients treated with sorafenib, supporting the hypothesis that treatment with sorafenib alters keratinocyte proliferation and differentiation.¹⁵ In addition, B-Raf inhibitors such as imatinib are known to induce or exacerbate psoriasiform dermatitis.¹⁶ The activity of sorafenib resulting in psoriasis may be specific to RAF kinase inhibition, as there are no reports in the literature that describe psoriasiform dermatitis with agents that preferentially block other sorafenib targets such as VEGF receptor, stem cell growth factor receptor, or platelet-derived growth factor receptor. Future studies are needed to fully elucidate the underlying mechanisms by which sorafenib induces or exacerbates psoriasiform dermatitis and whether the severity of the drug eruption correlates with the antitumor efficacy of sorafenib.

Conclusion

Although psoriasiform drug eruptions secondary to sorafenib are not life-threatening, they impact quality of life with associated pain, pruritus, infection, and limitation of daily activities. Dose reduction or discontinuation of sorafenib resulted in resolution of the psoriasiform dermatitis; however, as demonstrated in 3 cases (including patient 3),^1,2 psoriasiform dermatitis can be managed while maintaining the patient on sorafenib so that treatment of the malignancy is not compromised.

The expanded use of targeted anticancer agents such as sorafenib has revealed a growing spectrum of adverse cutaneous eruptions. We describe 3 patients with sorafenib-induced psoriasiform dermatitis and review the literature of only 10 other similar reported cases based on a search of PubMed, Web of Science, and American Society of Clinical Oncology abstracts using the terms psoriasis or psoriasiform dermatitis and sorafenib.^1-10 We seek to increase awareness of this particular drug eruption in response to sorafenib and to describe potential effective treatment options, especially when sorafenib cannot be discontinued.

Case Reports

Patient 1
A 68-year-old man with chronic hepatitis B infection and hepatocellular carcinoma (HCC) was started on sorafenib 400 mg daily. After 2 months of treatment, he developed painful hyperkeratotic lesions on the bilateral palms and soles with formation of calluses and superficial blisters on an erythematous base that was consistent with hand-foot skin reaction (HFSR). He also had numerous erythematous thin papules and plaques with adherent white scale and yellow crust on the bilateral thighs, lower legs, forearms, dorsal hands, abdomen, back, and buttocks (Figure 1). He had no personal or family history of psoriasis, and blood tests were unremarkable. Histologic analysis of punch biopsies from the buttocks and right leg revealed focal parakeratosis with neutrophils and serous crust, acanthosis, mild spongiosis, and lymphocytes at the dermoepidermal junction and surrounding dermal vessels, consistent with psoriasiform dermatitis (Figure 2). Sorafenib was discontinued and the eruption began to resolve within a week. A lower dose of sorafenib (200 mg daily) was attempted and the psoriasiform eruption recurred.

Patient 2
An 82-year-old man with chronic hepatitis B infection and HCC with lung metastasis was treated with sorafenib 400 mg daily. One week after treatment, he developed painful, thick, erythematous lesions on acral surfaces, consistent with HFSR. The sorafenib dose was decreased to 200 mg daily and HFSR resolved. Four months later, he developed well-demarcated, erythematous, scaly plaques with peripheral pustules on the right thigh (Figure 3) and right shin. He had no personal or family history of psoriasis, and blood tests were unremarkable. Samples from the pustules were taken for bacterial culture and fungal stain, but both were negative. Histologic analysis of a punch biopsy from the right thigh revealed necrotic parakeratosis, spongiform pustules, mild acanthosis, and a perivascular lymphocytic infiltrate with many neutrophils in the dermis. These findings suggested a diagnosis of pustular psoriasis, pustular drug eruption, or acute generalized exanthematous pustulosis. Treatment was initiated with mometasone cream. The patient subsequently developed hemoptysis and ascites from sorafenib. Sorafenib was discontinued and his skin eruption gradually resolved.

Comment

Sorafenib is an oral tyrosine kinase inhibitor that blocks tumor cell proliferation and angiogenesis due to its activity against vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, stem cell growth factor receptor, and rapidly accelerated fibrosarcoma kinases.¹¹ It is primarily used for the treatment of solid tumors, such as advanced renal cell carcinoma, unresectable HCC, and thyroid carcinoma, and more recently has been expanded for treatment of AML due to potential inhibition of FMS-like tyrosine kinase 3 receptor. Although dermatologic toxicity is a common adverse event during treatment with sorafenib,¹¹ reports of psoriasiform drug eruptions are rare.

Review of Cases
Based on our literature search, there are 10 previously reported cases of psoriasiform drug eruption secondary to sorafenib. Of the 13 total cases (including the 3 patients in this report), 7 patients had a history of psoriasis; most were middle-aged men; and the treatment with sorafenib was for solid tumors, primarily HCC with the exception of patient 3 from the current report who was treated for AML (Table). In all cases, the dose of sorafenib ranged from 200 to 800 mg daily. In 5 cases, HFSR preceded (as with patient 2 in the current report) or presented concurrently (as with patient 1 in the current report) with the onset of psoriasiform rash.^1,3,5

Vascular endothelial growth factor is overexpressed on psoriatic keratinocytes, contributes to epidermal hyperplasia, and induces angiogenesis in the dermis.¹² The development of psoriasiform eruptions in patients treated with sorafenib seems paradoxical, as this drug has been considered as potential therapy for psoriasis due to its ability to block VEGF receptor signaling. Indeed, an improvement of psoriasis has been reported in 1 case of a patient treated with sorafenib¹³ and in multiple patients with psoriasis treated with other VEGF antagonists (eg, bevacizumab).¹⁴ The underlying mechanisms by which sorafenib induced or exacerbated psoriasis are not entirely clear. Palmoplantar hyperkeratosis, keratosis pilaris–like eruption, multiple cysts, eruptive keratoacanthomas, and squamous cell carcinoma have been described in patients treated with sorafenib, supporting the hypothesis that treatment with sorafenib alters keratinocyte proliferation and differentiation.¹⁵ In addition, B-Raf inhibitors such as imatinib are known to induce or exacerbate psoriasiform dermatitis.¹⁶ The activity of sorafenib resulting in psoriasis may be specific to RAF kinase inhibition, as there are no reports in the literature that describe psoriasiform dermatitis with agents that preferentially block other sorafenib targets such as VEGF receptor, stem cell growth factor receptor, or platelet-derived growth factor receptor. Future studies are needed to fully elucidate the underlying mechanisms by which sorafenib induces or exacerbates psoriasiform dermatitis and whether the severity of the drug eruption correlates with the antitumor efficacy of sorafenib.

Conclusion

Although psoriasiform drug eruptions secondary to sorafenib are not life-threatening, they impact quality of life with associated pain, pruritus, infection, and limitation of daily activities. Dose reduction or discontinuation of sorafenib resulted in resolution of the psoriasiform dermatitis; however, as demonstrated in 3 cases (including patient 3),^1,2 psoriasiform dermatitis can be managed while maintaining the patient on sorafenib so that treatment of the malignancy is not compromised.

The expanded use of targeted anticancer agents such as sorafenib has revealed a growing spectrum of adverse cutaneous eruptions. We describe 3 patients with sorafenib-induced psoriasiform dermatitis and review the literature of only 10 other similar reported cases based on a search of PubMed, Web of Science, and American Society of Clinical Oncology abstracts using the terms psoriasis or psoriasiform dermatitis and sorafenib.^1-10 We seek to increase awareness of this particular drug eruption in response to sorafenib and to describe potential effective treatment options, especially when sorafenib cannot be discontinued.

Case Reports

Patient 1
A 68-year-old man with chronic hepatitis B infection and hepatocellular carcinoma (HCC) was started on sorafenib 400 mg daily. After 2 months of treatment, he developed painful hyperkeratotic lesions on the bilateral palms and soles with formation of calluses and superficial blisters on an erythematous base that was consistent with hand-foot skin reaction (HFSR). He also had numerous erythematous thin papules and plaques with adherent white scale and yellow crust on the bilateral thighs, lower legs, forearms, dorsal hands, abdomen, back, and buttocks (Figure 1). He had no personal or family history of psoriasis, and blood tests were unremarkable. Histologic analysis of punch biopsies from the buttocks and right leg revealed focal parakeratosis with neutrophils and serous crust, acanthosis, mild spongiosis, and lymphocytes at the dermoepidermal junction and surrounding dermal vessels, consistent with psoriasiform dermatitis (Figure 2). Sorafenib was discontinued and the eruption began to resolve within a week. A lower dose of sorafenib (200 mg daily) was attempted and the psoriasiform eruption recurred.

Patient 2
An 82-year-old man with chronic hepatitis B infection and HCC with lung metastasis was treated with sorafenib 400 mg daily. One week after treatment, he developed painful, thick, erythematous lesions on acral surfaces, consistent with HFSR. The sorafenib dose was decreased to 200 mg daily and HFSR resolved. Four months later, he developed well-demarcated, erythematous, scaly plaques with peripheral pustules on the right thigh (Figure 3) and right shin. He had no personal or family history of psoriasis, and blood tests were unremarkable. Samples from the pustules were taken for bacterial culture and fungal stain, but both were negative. Histologic analysis of a punch biopsy from the right thigh revealed necrotic parakeratosis, spongiform pustules, mild acanthosis, and a perivascular lymphocytic infiltrate with many neutrophils in the dermis. These findings suggested a diagnosis of pustular psoriasis, pustular drug eruption, or acute generalized exanthematous pustulosis. Treatment was initiated with mometasone cream. The patient subsequently developed hemoptysis and ascites from sorafenib. Sorafenib was discontinued and his skin eruption gradually resolved.

Comment

Sorafenib is an oral tyrosine kinase inhibitor that blocks tumor cell proliferation and angiogenesis due to its activity against vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor, stem cell growth factor receptor, and rapidly accelerated fibrosarcoma kinases.¹¹ It is primarily used for the treatment of solid tumors, such as advanced renal cell carcinoma, unresectable HCC, and thyroid carcinoma, and more recently has been expanded for treatment of AML due to potential inhibition of FMS-like tyrosine kinase 3 receptor. Although dermatologic toxicity is a common adverse event during treatment with sorafenib,¹¹ reports of psoriasiform drug eruptions are rare.

Review of Cases
Based on our literature search, there are 10 previously reported cases of psoriasiform drug eruption secondary to sorafenib. Of the 13 total cases (including the 3 patients in this report), 7 patients had a history of psoriasis; most were middle-aged men; and the treatment with sorafenib was for solid tumors, primarily HCC with the exception of patient 3 from the current report who was treated for AML (Table). In all cases, the dose of sorafenib ranged from 200 to 800 mg daily. In 5 cases, HFSR preceded (as with patient 2 in the current report) or presented concurrently (as with patient 1 in the current report) with the onset of psoriasiform rash.^1,3,5

Vascular endothelial growth factor is overexpressed on psoriatic keratinocytes, contributes to epidermal hyperplasia, and induces angiogenesis in the dermis.¹² The development of psoriasiform eruptions in patients treated with sorafenib seems paradoxical, as this drug has been considered as potential therapy for psoriasis due to its ability to block VEGF receptor signaling. Indeed, an improvement of psoriasis has been reported in 1 case of a patient treated with sorafenib¹³ and in multiple patients with psoriasis treated with other VEGF antagonists (eg, bevacizumab).¹⁴ The underlying mechanisms by which sorafenib induced or exacerbated psoriasis are not entirely clear. Palmoplantar hyperkeratosis, keratosis pilaris–like eruption, multiple cysts, eruptive keratoacanthomas, and squamous cell carcinoma have been described in patients treated with sorafenib, supporting the hypothesis that treatment with sorafenib alters keratinocyte proliferation and differentiation.¹⁵ In addition, B-Raf inhibitors such as imatinib are known to induce or exacerbate psoriasiform dermatitis.¹⁶ The activity of sorafenib resulting in psoriasis may be specific to RAF kinase inhibition, as there are no reports in the literature that describe psoriasiform dermatitis with agents that preferentially block other sorafenib targets such as VEGF receptor, stem cell growth factor receptor, or platelet-derived growth factor receptor. Future studies are needed to fully elucidate the underlying mechanisms by which sorafenib induces or exacerbates psoriasiform dermatitis and whether the severity of the drug eruption correlates with the antitumor efficacy of sorafenib.

Conclusion

Although psoriasiform drug eruptions secondary to sorafenib are not life-threatening, they impact quality of life with associated pain, pruritus, infection, and limitation of daily activities. Dose reduction or discontinuation of sorafenib resulted in resolution of the psoriasiform dermatitis; however, as demonstrated in 3 cases (including patient 3),^1,2 psoriasiform dermatitis can be managed while maintaining the patient on sorafenib so that treatment of the malignancy is not compromised.

Higher body mass index and moderate – but not heavy – drinking may increase the risk of individuals with psoriasis going on to develop psoriatic arthritis, a study has found.

Around one in five people with psoriasis will develop psoriatic arthritis (PsA), wrote Amelia Green of the University of Bath (England) and coauthors in the British Journal of Dermatology.

Previous studies have explored possible links between obesity, alcohol consumption, or smoking, and an increased risk of developing psoriatic arthritis. However, some of these studies found conflicting results or had limitations such as measuring only a single exposure.

In a cohort study, the Ms. Green and her colleagues examined data from the U.K. Clinical Practice Research Datalink for 90,189 individuals with psoriasis, 1,409 of whom were subsequently also diagnosed with psoriatic arthritis.

The analysis showed a significant association between increasing body mass index (BMI) and increasing odds of developing psoriatic arthritis. Compared with individuals with a BMI below 25 kg/m², those with a BMI of 25.0-29.9 had a 79% greater odds of psoriatic arthritis, those with a BMI of 30.0-34.9 had a 2.10-fold greater odds, and those with a BMI at or above 35 had a 2.68-fold greater odds of developing psoriatic arthritis (P for trend less than .001). Adjustment for potential confounders such as sex, age, duration and severity of psoriasis, diabetes, smoking, and alcohol use slightly attenuated the association, but it remained statistically significant.

Researchers also examined the cumulative effect of lower BMIs over time, and found that over a 10-year period, reductions in BMI were associated with reductions in the risk of developing PsA, compared with remaining at the same BMI over that time.

“Here we have shown for the first time that losing weight over time could reduce the risk of developing PsA in a population with documented psoriasis,” the authors wrote. “As the effect of obesity on the risk of developing PsA may in fact occur with some delay and change over time, our analysis took into account both updated BMI measurements over time and the possible nonlinear and cumulative effects of BMI, which have not previously been investigated.”

Commenting on the mechanisms underlying the association between obesity and the development of PsA, the authors noted that adipose tissue is a source of inflammatory mediators such as adipokines and proinflammatory cytokines, which could lead to the development of PsA. Increasing body weight also could cause microtraumas of the connective tissue between tendon and bone, which may act as an initiating pathogenic event for PsA.

Moderate drinkers – defined as 0.1–3.0 drinks per day ­– had 57% higher odds of developing PsA when compared with nondrinkers, but former drinkers or heavy drinkers did not have an increased risk.

The study also didn’t see any effect of either past or current smoking on the risk of PsA, although there was a nonsignificant interaction with obesity that hinted at increased odds.

“While we found no association between smoking status and the development of PsA in people with psoriasis, further analysis revealed that the effect of smoking on the risk of PsA was possibly mediated through the effect of BMI on PsA; in other words, the protective effect of smoking may be associated with lower BMI among smokers,” the authors wrote.

Patients who developed PsA were also more likely to be younger (mean age of 44.7 years vs. 48.5 years), have severe psoriasis, and have had the disease for a shorter duration.

The study was funded by the National Institute for Health Research, and the authors declared grants from the funder during the conduct of the study. No other conflicts of interest were declared.

SOURCE: Green A et al. Br J Dermatol. 2019 Jun 18. doi: 10.1111/bjd.18227

Higher body mass index and moderate – but not heavy – drinking may increase the risk of individuals with psoriasis going on to develop psoriatic arthritis, a study has found.

Around one in five people with psoriasis will develop psoriatic arthritis (PsA), wrote Amelia Green of the University of Bath (England) and coauthors in the British Journal of Dermatology.

Previous studies have explored possible links between obesity, alcohol consumption, or smoking, and an increased risk of developing psoriatic arthritis. However, some of these studies found conflicting results or had limitations such as measuring only a single exposure.

In a cohort study, the Ms. Green and her colleagues examined data from the U.K. Clinical Practice Research Datalink for 90,189 individuals with psoriasis, 1,409 of whom were subsequently also diagnosed with psoriatic arthritis.

The analysis showed a significant association between increasing body mass index (BMI) and increasing odds of developing psoriatic arthritis. Compared with individuals with a BMI below 25 kg/m², those with a BMI of 25.0-29.9 had a 79% greater odds of psoriatic arthritis, those with a BMI of 30.0-34.9 had a 2.10-fold greater odds, and those with a BMI at or above 35 had a 2.68-fold greater odds of developing psoriatic arthritis (P for trend less than .001). Adjustment for potential confounders such as sex, age, duration and severity of psoriasis, diabetes, smoking, and alcohol use slightly attenuated the association, but it remained statistically significant.

Researchers also examined the cumulative effect of lower BMIs over time, and found that over a 10-year period, reductions in BMI were associated with reductions in the risk of developing PsA, compared with remaining at the same BMI over that time.

“Here we have shown for the first time that losing weight over time could reduce the risk of developing PsA in a population with documented psoriasis,” the authors wrote. “As the effect of obesity on the risk of developing PsA may in fact occur with some delay and change over time, our analysis took into account both updated BMI measurements over time and the possible nonlinear and cumulative effects of BMI, which have not previously been investigated.”

Commenting on the mechanisms underlying the association between obesity and the development of PsA, the authors noted that adipose tissue is a source of inflammatory mediators such as adipokines and proinflammatory cytokines, which could lead to the development of PsA. Increasing body weight also could cause microtraumas of the connective tissue between tendon and bone, which may act as an initiating pathogenic event for PsA.

Moderate drinkers – defined as 0.1–3.0 drinks per day ­– had 57% higher odds of developing PsA when compared with nondrinkers, but former drinkers or heavy drinkers did not have an increased risk.

The study also didn’t see any effect of either past or current smoking on the risk of PsA, although there was a nonsignificant interaction with obesity that hinted at increased odds.

“While we found no association between smoking status and the development of PsA in people with psoriasis, further analysis revealed that the effect of smoking on the risk of PsA was possibly mediated through the effect of BMI on PsA; in other words, the protective effect of smoking may be associated with lower BMI among smokers,” the authors wrote.

Patients who developed PsA were also more likely to be younger (mean age of 44.7 years vs. 48.5 years), have severe psoriasis, and have had the disease for a shorter duration.

The study was funded by the National Institute for Health Research, and the authors declared grants from the funder during the conduct of the study. No other conflicts of interest were declared.

SOURCE: Green A et al. Br J Dermatol. 2019 Jun 18. doi: 10.1111/bjd.18227

Higher body mass index and moderate – but not heavy – drinking may increase the risk of individuals with psoriasis going on to develop psoriatic arthritis, a study has found.

Around one in five people with psoriasis will develop psoriatic arthritis (PsA), wrote Amelia Green of the University of Bath (England) and coauthors in the British Journal of Dermatology.

Previous studies have explored possible links between obesity, alcohol consumption, or smoking, and an increased risk of developing psoriatic arthritis. However, some of these studies found conflicting results or had limitations such as measuring only a single exposure.

In a cohort study, the Ms. Green and her colleagues examined data from the U.K. Clinical Practice Research Datalink for 90,189 individuals with psoriasis, 1,409 of whom were subsequently also diagnosed with psoriatic arthritis.

The analysis showed a significant association between increasing body mass index (BMI) and increasing odds of developing psoriatic arthritis. Compared with individuals with a BMI below 25 kg/m², those with a BMI of 25.0-29.9 had a 79% greater odds of psoriatic arthritis, those with a BMI of 30.0-34.9 had a 2.10-fold greater odds, and those with a BMI at or above 35 had a 2.68-fold greater odds of developing psoriatic arthritis (P for trend less than .001). Adjustment for potential confounders such as sex, age, duration and severity of psoriasis, diabetes, smoking, and alcohol use slightly attenuated the association, but it remained statistically significant.

Researchers also examined the cumulative effect of lower BMIs over time, and found that over a 10-year period, reductions in BMI were associated with reductions in the risk of developing PsA, compared with remaining at the same BMI over that time.

“Here we have shown for the first time that losing weight over time could reduce the risk of developing PsA in a population with documented psoriasis,” the authors wrote. “As the effect of obesity on the risk of developing PsA may in fact occur with some delay and change over time, our analysis took into account both updated BMI measurements over time and the possible nonlinear and cumulative effects of BMI, which have not previously been investigated.”

Commenting on the mechanisms underlying the association between obesity and the development of PsA, the authors noted that adipose tissue is a source of inflammatory mediators such as adipokines and proinflammatory cytokines, which could lead to the development of PsA. Increasing body weight also could cause microtraumas of the connective tissue between tendon and bone, which may act as an initiating pathogenic event for PsA.

Moderate drinkers – defined as 0.1–3.0 drinks per day ­– had 57% higher odds of developing PsA when compared with nondrinkers, but former drinkers or heavy drinkers did not have an increased risk.

The study also didn’t see any effect of either past or current smoking on the risk of PsA, although there was a nonsignificant interaction with obesity that hinted at increased odds.

“While we found no association between smoking status and the development of PsA in people with psoriasis, further analysis revealed that the effect of smoking on the risk of PsA was possibly mediated through the effect of BMI on PsA; in other words, the protective effect of smoking may be associated with lower BMI among smokers,” the authors wrote.

Patients who developed PsA were also more likely to be younger (mean age of 44.7 years vs. 48.5 years), have severe psoriasis, and have had the disease for a shorter duration.

The study was funded by the National Institute for Health Research, and the authors declared grants from the funder during the conduct of the study. No other conflicts of interest were declared.

SOURCE: Green A et al. Br J Dermatol. 2019 Jun 18. doi: 10.1111/bjd.18227

AUSTIN, TEX. – The way Kelly M. Cordoro sees it, the most difficult part of managing pediatric patients with severe psoriasis is not in the logistics of prescribing a drug, it’s deciding which drug to use for which patient.

“You can look up the dosing and frequency of these drugs; all of that’s available,” she said at the annual meeting of the Society for Pediatric Dermatology. “But how do we think about which drug for which patient? What are the considerations?”

Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, described psoriasis as an autoamplifying inflammatory cascade involving innate and adaptive immunity and noted that various components of that cascade represent treatment targets. “We don’t have a true comprehension of the pathophysiology of psoriasis, but as we learn the pathways, we’re targeting them,” she said. “You can target keratinocyte proliferation with drugs like retinoids and phototherapy. You can broadly target T cells, neutrophils, and dendritic cells with methotrexate, cyclosporine, and phototherapy. The newer drugs target the cytokine milieu, including TNF [tumor necrosis factor]–alpha, IL [interleukin]–17A, IL-12, and IL-23.”

There is no one right answer for which drug to prescribe, she continued, except in the cases of certain comorbidities, contraindications, and genetic variants. “For example, if a patient has psoriatic arthritis, then you have methotrexate and all of the biologics that might be disease modifying,” she said. “If a patient has inflammatory bowel disease, it’s critical to know that IL-17 inhibitors will flare that disease, but anti-TNF and IL-12 and IL-23 inhibitors are okay. If a patient has liver and kidney disease, you want to avoid methotrexate and cyclosporine. If there’s a female of childbearing potential you want to be very cautious with using retinoids. I think the harder question for us is, How about the rest of the patients?”

In addition to a drug’s mechanism of action, patient- and family-related factors play a role in deciding which agent to use. For example, does the patient prefer an oral or an injectable agent? Is the patient able to travel to a phototherapy center? Is it feasible for the family to manage visits for lab work and direct clinical monitoring? Does the family have a high level of health literacy and are you communicating with them in ways that facilitate shared decision making?

“The best way to choose a systemic therapy is to develop an individualized assessment of overall disease burden,” said Dr. Cordoro, who is also division chief of pediatric dermatology at UCSF. “Include psychological burden and subjective data in addition to objective measures like body surface area. Look for triggers. Infants are more commonly affected by viral infections and, in a subset, monogenic forms of psoriasis such as deficiency of interleukin 1 receptor antagonist [DIRA]. In general, we try to take a conservative approach in the developing child. As children hit early adolescence and become post pubertal, you have to start thinking about the psychosocial impact [of psoriasis], and we have to start treating patients with the consideration that chronic uncontrolled inflammation can potentially lead to comorbidities down the road. We see this in adults with severe psoriasis and early onset cardiovascular disease, the so-called psoriatic march from chronic inflammation to cardiovascular disease.”

Dr. Cordoro advises clinicians to rethink the conventional “therapeutic ladder” concept and embrace the idea of “finding the right tool for the job right now.” If a patient presents with a flare from a known trigger such as a strep infection, “maybe you want to treat with something more conservative,” she said. “Once you treat, and if the trigger has been managed, they might be better. But some patients will need the most aggressive treatment right out of the gate.”

Tried and true systemic therapies for psoriasis include methotrexate, cyclosporine, acitretin, and phototherapy, but none is approved by the Food and Drug Administration for use in children. “These drugs have decades of experience behind them,” Dr. Cordoro said. “Methotrexate is slow to start but has a sustained profile, so if you can get the patient to respond, that response tends to persist. Methotrexate also prevents the formation of antidrug antibodies, which is important if you are considering use of a biologic agent later on.”

Cyclosporine is best if you need a rapid rescue drug to get the disease under control before moving on to other options. “One in four patients relapse once cyclosporine is discontinued, so the benefit may not be as sustained as with methotrexate,” she said. “Acitretin is a really nice choice when you can’t or don’t want to immunosuppress the patient, and phototherapy is good if you can get it. The advantages of systemic therapies are that they’re easy on, easy off, and you can combine medications in severe situations. Almost all of these drugs can be combined with another, with few exceptions. I would caution that over immunosuppression is the biggest risk ... so this must be done carefully and only when necessary.”

Biologic agents such as TNF inhibitors and IL-12/23 inhibitors are playing an increasing role in pediatric psoriasis. They can be expensive and difficult for some insurance plans to cover, but offer the convenience of better efficacy and less frequent lab monitoring than conventional systemics. In the United States, etanercept and ustekinumab are approved for moderate to severe pediatric plaque psoriasis in patients as young as age 4 and 12 years, respectively. TNF inhibitors have accumulated the most data in children, while data are accumulating in trials of IL-17 inhibitors, IL-23 inhibitors, and PDE4 inhibitors.

“These drugs have reassuring safety profiles; low rates of infection and adverse reactions,” Dr. Cordoro said of biologic agents. “They’ve changed the landscape completely because now the expectation is complete or near-complete clearance. In contrast to the systemic agents, which may be started and stopped repeatedly, you need to think about continuous therapy, because these drugs are immunogenic,” she noted. “Whether antibodies against them become neutralizing or not is a different case. If a patient does have antibodies, it does not mean you have to stop the drug. Dose escalation can help. Increasing frequency of use of the drug can help, but patients will develop antibodies and it may result in loss of efficacy or reactions to the drug,” she added.

“When you’re thinking about using a biologic agent, think about patients who are chronic, moderate to severe, and who will need more long-term therapy. Most importantly, treatment should be individualized, as there is no ‘one size fits all’ approach.”

Dr. Cordoro disclosed that she is a member of the Celgene Corporation Scientific Steering Committee.

[email protected]

AUSTIN, TEX. – The way Kelly M. Cordoro sees it, the most difficult part of managing pediatric patients with severe psoriasis is not in the logistics of prescribing a drug, it’s deciding which drug to use for which patient.

“You can look up the dosing and frequency of these drugs; all of that’s available,” she said at the annual meeting of the Society for Pediatric Dermatology. “But how do we think about which drug for which patient? What are the considerations?”

Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, described psoriasis as an autoamplifying inflammatory cascade involving innate and adaptive immunity and noted that various components of that cascade represent treatment targets. “We don’t have a true comprehension of the pathophysiology of psoriasis, but as we learn the pathways, we’re targeting them,” she said. “You can target keratinocyte proliferation with drugs like retinoids and phototherapy. You can broadly target T cells, neutrophils, and dendritic cells with methotrexate, cyclosporine, and phototherapy. The newer drugs target the cytokine milieu, including TNF [tumor necrosis factor]–alpha, IL [interleukin]–17A, IL-12, and IL-23.”

There is no one right answer for which drug to prescribe, she continued, except in the cases of certain comorbidities, contraindications, and genetic variants. “For example, if a patient has psoriatic arthritis, then you have methotrexate and all of the biologics that might be disease modifying,” she said. “If a patient has inflammatory bowel disease, it’s critical to know that IL-17 inhibitors will flare that disease, but anti-TNF and IL-12 and IL-23 inhibitors are okay. If a patient has liver and kidney disease, you want to avoid methotrexate and cyclosporine. If there’s a female of childbearing potential you want to be very cautious with using retinoids. I think the harder question for us is, How about the rest of the patients?”

In addition to a drug’s mechanism of action, patient- and family-related factors play a role in deciding which agent to use. For example, does the patient prefer an oral or an injectable agent? Is the patient able to travel to a phototherapy center? Is it feasible for the family to manage visits for lab work and direct clinical monitoring? Does the family have a high level of health literacy and are you communicating with them in ways that facilitate shared decision making?

“The best way to choose a systemic therapy is to develop an individualized assessment of overall disease burden,” said Dr. Cordoro, who is also division chief of pediatric dermatology at UCSF. “Include psychological burden and subjective data in addition to objective measures like body surface area. Look for triggers. Infants are more commonly affected by viral infections and, in a subset, monogenic forms of psoriasis such as deficiency of interleukin 1 receptor antagonist [DIRA]. In general, we try to take a conservative approach in the developing child. As children hit early adolescence and become post pubertal, you have to start thinking about the psychosocial impact [of psoriasis], and we have to start treating patients with the consideration that chronic uncontrolled inflammation can potentially lead to comorbidities down the road. We see this in adults with severe psoriasis and early onset cardiovascular disease, the so-called psoriatic march from chronic inflammation to cardiovascular disease.”

Dr. Cordoro advises clinicians to rethink the conventional “therapeutic ladder” concept and embrace the idea of “finding the right tool for the job right now.” If a patient presents with a flare from a known trigger such as a strep infection, “maybe you want to treat with something more conservative,” she said. “Once you treat, and if the trigger has been managed, they might be better. But some patients will need the most aggressive treatment right out of the gate.”

Tried and true systemic therapies for psoriasis include methotrexate, cyclosporine, acitretin, and phototherapy, but none is approved by the Food and Drug Administration for use in children. “These drugs have decades of experience behind them,” Dr. Cordoro said. “Methotrexate is slow to start but has a sustained profile, so if you can get the patient to respond, that response tends to persist. Methotrexate also prevents the formation of antidrug antibodies, which is important if you are considering use of a biologic agent later on.”

Cyclosporine is best if you need a rapid rescue drug to get the disease under control before moving on to other options. “One in four patients relapse once cyclosporine is discontinued, so the benefit may not be as sustained as with methotrexate,” she said. “Acitretin is a really nice choice when you can’t or don’t want to immunosuppress the patient, and phototherapy is good if you can get it. The advantages of systemic therapies are that they’re easy on, easy off, and you can combine medications in severe situations. Almost all of these drugs can be combined with another, with few exceptions. I would caution that over immunosuppression is the biggest risk ... so this must be done carefully and only when necessary.”

Biologic agents such as TNF inhibitors and IL-12/23 inhibitors are playing an increasing role in pediatric psoriasis. They can be expensive and difficult for some insurance plans to cover, but offer the convenience of better efficacy and less frequent lab monitoring than conventional systemics. In the United States, etanercept and ustekinumab are approved for moderate to severe pediatric plaque psoriasis in patients as young as age 4 and 12 years, respectively. TNF inhibitors have accumulated the most data in children, while data are accumulating in trials of IL-17 inhibitors, IL-23 inhibitors, and PDE4 inhibitors.

“These drugs have reassuring safety profiles; low rates of infection and adverse reactions,” Dr. Cordoro said of biologic agents. “They’ve changed the landscape completely because now the expectation is complete or near-complete clearance. In contrast to the systemic agents, which may be started and stopped repeatedly, you need to think about continuous therapy, because these drugs are immunogenic,” she noted. “Whether antibodies against them become neutralizing or not is a different case. If a patient does have antibodies, it does not mean you have to stop the drug. Dose escalation can help. Increasing frequency of use of the drug can help, but patients will develop antibodies and it may result in loss of efficacy or reactions to the drug,” she added.

“When you’re thinking about using a biologic agent, think about patients who are chronic, moderate to severe, and who will need more long-term therapy. Most importantly, treatment should be individualized, as there is no ‘one size fits all’ approach.”

Dr. Cordoro disclosed that she is a member of the Celgene Corporation Scientific Steering Committee.

[email protected]

AUSTIN, TEX. – The way Kelly M. Cordoro sees it, the most difficult part of managing pediatric patients with severe psoriasis is not in the logistics of prescribing a drug, it’s deciding which drug to use for which patient.

“You can look up the dosing and frequency of these drugs; all of that’s available,” she said at the annual meeting of the Society for Pediatric Dermatology. “But how do we think about which drug for which patient? What are the considerations?”

Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, described psoriasis as an autoamplifying inflammatory cascade involving innate and adaptive immunity and noted that various components of that cascade represent treatment targets. “We don’t have a true comprehension of the pathophysiology of psoriasis, but as we learn the pathways, we’re targeting them,” she said. “You can target keratinocyte proliferation with drugs like retinoids and phototherapy. You can broadly target T cells, neutrophils, and dendritic cells with methotrexate, cyclosporine, and phototherapy. The newer drugs target the cytokine milieu, including TNF [tumor necrosis factor]–alpha, IL [interleukin]–17A, IL-12, and IL-23.”

There is no one right answer for which drug to prescribe, she continued, except in the cases of certain comorbidities, contraindications, and genetic variants. “For example, if a patient has psoriatic arthritis, then you have methotrexate and all of the biologics that might be disease modifying,” she said. “If a patient has inflammatory bowel disease, it’s critical to know that IL-17 inhibitors will flare that disease, but anti-TNF and IL-12 and IL-23 inhibitors are okay. If a patient has liver and kidney disease, you want to avoid methotrexate and cyclosporine. If there’s a female of childbearing potential you want to be very cautious with using retinoids. I think the harder question for us is, How about the rest of the patients?”

In addition to a drug’s mechanism of action, patient- and family-related factors play a role in deciding which agent to use. For example, does the patient prefer an oral or an injectable agent? Is the patient able to travel to a phototherapy center? Is it feasible for the family to manage visits for lab work and direct clinical monitoring? Does the family have a high level of health literacy and are you communicating with them in ways that facilitate shared decision making?

“The best way to choose a systemic therapy is to develop an individualized assessment of overall disease burden,” said Dr. Cordoro, who is also division chief of pediatric dermatology at UCSF. “Include psychological burden and subjective data in addition to objective measures like body surface area. Look for triggers. Infants are more commonly affected by viral infections and, in a subset, monogenic forms of psoriasis such as deficiency of interleukin 1 receptor antagonist [DIRA]. In general, we try to take a conservative approach in the developing child. As children hit early adolescence and become post pubertal, you have to start thinking about the psychosocial impact [of psoriasis], and we have to start treating patients with the consideration that chronic uncontrolled inflammation can potentially lead to comorbidities down the road. We see this in adults with severe psoriasis and early onset cardiovascular disease, the so-called psoriatic march from chronic inflammation to cardiovascular disease.”

Dr. Cordoro advises clinicians to rethink the conventional “therapeutic ladder” concept and embrace the idea of “finding the right tool for the job right now.” If a patient presents with a flare from a known trigger such as a strep infection, “maybe you want to treat with something more conservative,” she said. “Once you treat, and if the trigger has been managed, they might be better. But some patients will need the most aggressive treatment right out of the gate.”

Tried and true systemic therapies for psoriasis include methotrexate, cyclosporine, acitretin, and phototherapy, but none is approved by the Food and Drug Administration for use in children. “These drugs have decades of experience behind them,” Dr. Cordoro said. “Methotrexate is slow to start but has a sustained profile, so if you can get the patient to respond, that response tends to persist. Methotrexate also prevents the formation of antidrug antibodies, which is important if you are considering use of a biologic agent later on.”

Cyclosporine is best if you need a rapid rescue drug to get the disease under control before moving on to other options. “One in four patients relapse once cyclosporine is discontinued, so the benefit may not be as sustained as with methotrexate,” she said. “Acitretin is a really nice choice when you can’t or don’t want to immunosuppress the patient, and phototherapy is good if you can get it. The advantages of systemic therapies are that they’re easy on, easy off, and you can combine medications in severe situations. Almost all of these drugs can be combined with another, with few exceptions. I would caution that over immunosuppression is the biggest risk ... so this must be done carefully and only when necessary.”

Biologic agents such as TNF inhibitors and IL-12/23 inhibitors are playing an increasing role in pediatric psoriasis. They can be expensive and difficult for some insurance plans to cover, but offer the convenience of better efficacy and less frequent lab monitoring than conventional systemics. In the United States, etanercept and ustekinumab are approved for moderate to severe pediatric plaque psoriasis in patients as young as age 4 and 12 years, respectively. TNF inhibitors have accumulated the most data in children, while data are accumulating in trials of IL-17 inhibitors, IL-23 inhibitors, and PDE4 inhibitors.

“These drugs have reassuring safety profiles; low rates of infection and adverse reactions,” Dr. Cordoro said of biologic agents. “They’ve changed the landscape completely because now the expectation is complete or near-complete clearance. In contrast to the systemic agents, which may be started and stopped repeatedly, you need to think about continuous therapy, because these drugs are immunogenic,” she noted. “Whether antibodies against them become neutralizing or not is a different case. If a patient does have antibodies, it does not mean you have to stop the drug. Dose escalation can help. Increasing frequency of use of the drug can help, but patients will develop antibodies and it may result in loss of efficacy or reactions to the drug,” she added.

“When you’re thinking about using a biologic agent, think about patients who are chronic, moderate to severe, and who will need more long-term therapy. Most importantly, treatment should be individualized, as there is no ‘one size fits all’ approach.”

Dr. Cordoro disclosed that she is a member of the Celgene Corporation Scientific Steering Committee.

[email protected]

Verrucous psoriasis: A rare variant of psoriasis masquerading as verrucous carcinoma.

Garvie K, McGinley Simpson M, Logemann N, Lackey J. JAAD Case Rep. 2019 Aug 5;5(8):723-725.

Verrucous psoriasis is a rare variant of psoriasis characterized by hyperkeratotic, papillomatous plaques that clinically resemble verrucous carcinoma in lesion appearance and distribution. It is amenable to medical treatments. Conversely, verrucous carcinoma, a rare subtype of well-differentiated squamous cell carcinoma, is treated with surgical excision. Histologically, they may be difficult to differentiate. This case report presents a patient with verrucous psoriasis of the heal that was initially diagnosed as verrucous carcinoma and excised.

Re-Categorization of Psoriasis Severity: Delphi Consensus from the International Psoriasis Council.

Strober B, Ryan C, van de Kerkhof P, et al. J Am Acad Dermatol. 2019 Aug 16.

This consensus statement on the classification of psoriasis severity preferentially ranked seven severity definitions. This most preferred statement rejects the mild, moderate and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic therapy; the latter are patients who meet at least one of the following criteria: 1) BSA > 10%, 2) Disease involving special areas, 3) Failure of topical therapy.

Gluten intake and risk of psoriasis, psoriatic arthritis and atopic dermatitis among US women.

Drucker AM, Qureshi AA, Thompson JM, Li T, Cho E. J Am Acad Dermatol. 2019 Aug 9.

Associations between gluten intake and psoriasis, psoriatic arthritis and atopic dermatitis are poorly understood. Gluten content of participants' diet was calculated every four years using food frequency questionnaires. Disease outcomes were assessed by self-report and subsequently validated.

Psoriasis and Mortality in the US: Data from the National Health and Nutrition Examination Survey.

Semenov YR, Herbosa CM, Rogers AT, et al. J Am Acad Dermatol. 2019 Aug 12.

In this retrospective population-based cohort study of adults and adolescents > 10 years (n=13,031) who participated in National Health and Nutrition Examination Surveys (2003-2006; 2009-2010), psoriasis was present in 2.7% of the study population. Over an average 52.3 months median follow-up, psoriasis was significantly associated with increased mortality risk. This relationship is partially mediated by an increased prevalence of cardiovascular, infectious, and neoplastic disorders seen among psoriatics.

Ostraceous Psoriasis Presenting as Koebner Phenomenon in a Tattoo.

Reinhart J, Willett M, Gibbs N. J Drugs Dermatol. 2019 Aug 1;18(8):825-826.

Psoriasis ostracea is defined as having pronounced adherent scales resembling an oyster shell. Many ostraceous cases occur as generalized outbreaks in patients with long-standing history of psoriasis. Rarely does this variant occur as a direct flare from a cutaneous insult. In these situations, when a pre-existing dermatosis appears in response to a traumatic insult to skin, the process is referred to as the Koebner phenomenon. In addition to lichen planus and vitiligo, psoriasis is a commonly known condition that can present as a Koebner reaction. In this atypical case, the authors present a 21-year-old male with remarkable ostraceous psoriatic lesions precipitated by an upper arm tattoo, demonstrating the Koebner phenomenon.

Verrucous psoriasis: A rare variant of psoriasis masquerading as verrucous carcinoma.

Garvie K, McGinley Simpson M, Logemann N, Lackey J. JAAD Case Rep. 2019 Aug 5;5(8):723-725.

Verrucous psoriasis is a rare variant of psoriasis characterized by hyperkeratotic, papillomatous plaques that clinically resemble verrucous carcinoma in lesion appearance and distribution. It is amenable to medical treatments. Conversely, verrucous carcinoma, a rare subtype of well-differentiated squamous cell carcinoma, is treated with surgical excision. Histologically, they may be difficult to differentiate. This case report presents a patient with verrucous psoriasis of the heal that was initially diagnosed as verrucous carcinoma and excised.

Re-Categorization of Psoriasis Severity: Delphi Consensus from the International Psoriasis Council.

Strober B, Ryan C, van de Kerkhof P, et al. J Am Acad Dermatol. 2019 Aug 16.

This consensus statement on the classification of psoriasis severity preferentially ranked seven severity definitions. This most preferred statement rejects the mild, moderate and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic therapy; the latter are patients who meet at least one of the following criteria: 1) BSA > 10%, 2) Disease involving special areas, 3) Failure of topical therapy.

Gluten intake and risk of psoriasis, psoriatic arthritis and atopic dermatitis among US women.

Drucker AM, Qureshi AA, Thompson JM, Li T, Cho E. J Am Acad Dermatol. 2019 Aug 9.

Associations between gluten intake and psoriasis, psoriatic arthritis and atopic dermatitis are poorly understood. Gluten content of participants' diet was calculated every four years using food frequency questionnaires. Disease outcomes were assessed by self-report and subsequently validated.

Psoriasis and Mortality in the US: Data from the National Health and Nutrition Examination Survey.

Semenov YR, Herbosa CM, Rogers AT, et al. J Am Acad Dermatol. 2019 Aug 12.

In this retrospective population-based cohort study of adults and adolescents > 10 years (n=13,031) who participated in National Health and Nutrition Examination Surveys (2003-2006; 2009-2010), psoriasis was present in 2.7% of the study population. Over an average 52.3 months median follow-up, psoriasis was significantly associated with increased mortality risk. This relationship is partially mediated by an increased prevalence of cardiovascular, infectious, and neoplastic disorders seen among psoriatics.

Ostraceous Psoriasis Presenting as Koebner Phenomenon in a Tattoo.

Reinhart J, Willett M, Gibbs N. J Drugs Dermatol. 2019 Aug 1;18(8):825-826.

Psoriasis ostracea is defined as having pronounced adherent scales resembling an oyster shell. Many ostraceous cases occur as generalized outbreaks in patients with long-standing history of psoriasis. Rarely does this variant occur as a direct flare from a cutaneous insult. In these situations, when a pre-existing dermatosis appears in response to a traumatic insult to skin, the process is referred to as the Koebner phenomenon. In addition to lichen planus and vitiligo, psoriasis is a commonly known condition that can present as a Koebner reaction. In this atypical case, the authors present a 21-year-old male with remarkable ostraceous psoriatic lesions precipitated by an upper arm tattoo, demonstrating the Koebner phenomenon.

Verrucous psoriasis: A rare variant of psoriasis masquerading as verrucous carcinoma.

Garvie K, McGinley Simpson M, Logemann N, Lackey J. JAAD Case Rep. 2019 Aug 5;5(8):723-725.

Verrucous psoriasis is a rare variant of psoriasis characterized by hyperkeratotic, papillomatous plaques that clinically resemble verrucous carcinoma in lesion appearance and distribution. It is amenable to medical treatments. Conversely, verrucous carcinoma, a rare subtype of well-differentiated squamous cell carcinoma, is treated with surgical excision. Histologically, they may be difficult to differentiate. This case report presents a patient with verrucous psoriasis of the heal that was initially diagnosed as verrucous carcinoma and excised.

Re-Categorization of Psoriasis Severity: Delphi Consensus from the International Psoriasis Council.

Strober B, Ryan C, van de Kerkhof P, et al. J Am Acad Dermatol. 2019 Aug 16.

This consensus statement on the classification of psoriasis severity preferentially ranked seven severity definitions. This most preferred statement rejects the mild, moderate and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic therapy; the latter are patients who meet at least one of the following criteria: 1) BSA > 10%, 2) Disease involving special areas, 3) Failure of topical therapy.

Gluten intake and risk of psoriasis, psoriatic arthritis and atopic dermatitis among US women.

Drucker AM, Qureshi AA, Thompson JM, Li T, Cho E. J Am Acad Dermatol. 2019 Aug 9.

Associations between gluten intake and psoriasis, psoriatic arthritis and atopic dermatitis are poorly understood. Gluten content of participants' diet was calculated every four years using food frequency questionnaires. Disease outcomes were assessed by self-report and subsequently validated.

Psoriasis and Mortality in the US: Data from the National Health and Nutrition Examination Survey.

Semenov YR, Herbosa CM, Rogers AT, et al. J Am Acad Dermatol. 2019 Aug 12.

In this retrospective population-based cohort study of adults and adolescents > 10 years (n=13,031) who participated in National Health and Nutrition Examination Surveys (2003-2006; 2009-2010), psoriasis was present in 2.7% of the study population. Over an average 52.3 months median follow-up, psoriasis was significantly associated with increased mortality risk. This relationship is partially mediated by an increased prevalence of cardiovascular, infectious, and neoplastic disorders seen among psoriatics.

Ostraceous Psoriasis Presenting as Koebner Phenomenon in a Tattoo.

Reinhart J, Willett M, Gibbs N. J Drugs Dermatol. 2019 Aug 1;18(8):825-826.

Psoriasis ostracea is defined as having pronounced adherent scales resembling an oyster shell. Many ostraceous cases occur as generalized outbreaks in patients with long-standing history of psoriasis. Rarely does this variant occur as a direct flare from a cutaneous insult. In these situations, when a pre-existing dermatosis appears in response to a traumatic insult to skin, the process is referred to as the Koebner phenomenon. In addition to lichen planus and vitiligo, psoriasis is a commonly known condition that can present as a Koebner reaction. In this atypical case, the authors present a 21-year-old male with remarkable ostraceous psoriatic lesions precipitated by an upper arm tattoo, demonstrating the Koebner phenomenon.