Alexa B. Kimball, MD, MPH

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Itch is one of the most protean manifestations of skin disease and can take a substantial physical and emotional toll on patients. For physicians, it is a frequent—if often dreaded—patient concern with a rising incidence. Lack of specific itch therapies as well as associations with multiple dermatologic conditions, including xerosis, psoriasis, atopic dermatitis, cutaneous lymphoma, contact dermatitis, and internal malignancies, make management of these itchy patients challenging and deserving of our attention. Studies evaluating patients with chronic pruritus identified a considerable impact on health-related quality of life, including development of depression, inability to perform activities of daily living, and sleep difficulties. ¹

How to Classify Itching

Itch, or pruritus, originally was defined as an unpleasant sensation that provokes the desire to scratch,² but this definition likely limits our ability to assess itch. The urge to scratch the skin to relieve the itch is sometimes a reflex of the muscles triggered by the spinal cord that can be either conscious or unconscious. If 2 patients present with itch, does the patient with more excoriated skin experience more severe itch? Conversely, does the patient who scratches less have an equivalent decrease in itch severity? Although it is tempting to quantify itch through physical signs such as excoriations, it ultimately is a subjective symptom that is difficult to assess.

Pain is another complex subjective symptom but is one that has been better studied. A previous intensity theory postulated that itch is a form of pain: low-intensity noxious stimuli are perceived as itch, while high-intensity stimuli are perceived as pain. Over time, our understanding of itch evolved, and it became clear that a specific neuronal pathway for itch also exists.³ However, the pathophysiology of itch and pain remain intertwined. Scratching may elicit pain, providing a change in sensation that replaces the itch, whereas opioid analgesics suppress pain but may worsen the itch.

We are gaining a better understanding of the biology and classification of itch, which will hopefully enable the development of new measures to accurately assess itch. Four main categories of itch currently exist: neurogenic, psychogenic, neuropathic, and pruritoceptive.⁴ Patients may have one or multiple types of itch, which can be differentiated clinically and biochemically. Neurogenic (also known as systemic) itch is transmitted via the central nervous system with possible involvement of itch-specific neurons in the spinal cord and encompasses itch associated with pruritus from other organ systems. As the term implies, psychogenic itch is associated with psychiatric disorders. Neuropathic itch is generated from the inappropriate firing of peripheral or central sensory neurons in the absence of pruritogenic stimuli, which can be seen in notalgia paresthetica, brachioradial pruritus, and postherpetic neuralgia. Pruritoceptive itch most commonly is encountered in dermatology and is associated with skin inflammation or other dermatoses.⁴

How to Assess Itch Quantitatively

There currently are 2 major questions about quantitative assessments of itch. First, how do we measure itch in studies that are designed to relieve a different skin disease that is associated with itch? Most clinical trials investigating therapeutic options for atopic dermatitis and psoriasis now include itch assessment and improvement as a secondary outcome. Second, how do we measure itch in studies that are designed with relief of itch as the primary end point? Both of these scenarios require a fundamental set of decisions. Itch clearly is a subjective experience, but it also is one that can be local, regional, generalized, or transitory. Just as with pain, an individual can be distracted from their itch to some extent and consequently experience it more acutely when there are fewer stimuli in their environment. Classically, patients will report that itching is worse at night, preventing them from sleeping. Sleep disruption previously has been demonstrated.⁵ Of course, the environment also can exacerbate itch, as dry air and in some cases humidity can flare the sensation.

Fundamentally, therefore, the questions that are asked to assess itch are incredibly relevant, and there is a matrix of possible avenues of inquiry. Should you measure the peak itch in one area or the peak itch overall? Is the duration, the frequency, or the persistence of the itching most relevant? What is the correct time frame in which to do an assessment: the last 24 hours, the last 48 hours, or the last week? Because these parameters have been so challenging, most investigators have used a visual analog scale, similar to what is used to assess pain, at a 24-hour interval to decrease recall bias. The most commonly employed tool is the itch numeric rating scale (NRS), which asks patients to rate their symptoms on a scale of 0 (no itch) to 10 (worst imaginable itch). Although the psychometric properties of the itch NRS have been validated, debate still exists as to whether the itch NRS is best administered at a specific time of day or if it should be updated to evaluate peak pruritus scores explicitly. Regardless, implementing these scales often is time consuming and burdensome in the clinical trial setting, as participants are asked to complete daily diaries at the same time each day using either paper forms or electronic tablets.

Once scores are collected, we then need to quantitate a meaningful difference in itch. For pain, there has been some acceptance of a 30% difference, or a 2-point reduction, as being clinically meaningful; however, there was substantial debate at the time of the approval of ixekizumab as to whether that was a similarly appropriate threshold for itch. Using data from ixekizumab phase 2 and phase 3 trials, a 4-point reduction in itch NRS was found to be optimal for evaluating clinically significant changes in moderate to severe psoriasis.⁶ A more recent study of the validity of the itch NRS in prurigo nodularis suggested a 1-point change was correlated with minimal clinical improvement.⁷ Thus, the interesting question of how assessment of itch varies across clinical trials and disease states needs to be raised. Psoriasis classically has been thought of as not particularly itchy, and atopic dermatitis and prurigo nodularis have been regarded as extraordinarily itchy, yet one study comparing baseline itch scores in psoriasis and atopic dermatitis suggested that the experience actually is somewhat similar.⁸

Final Thoughts

The subjective nature of itch makes NRSs our best option at this time, but the best disease severity assessment tools are objective, sensitive, and generalizable. Unfortunately, we do not have such tools available to us yet, but technology—smart devices to monitor nocturnal scratching and machine learning algorithms that use electromagnetic impact to capture motion associated with itching and scratching⁹—may offer new objective measures for itch that can be used to further validate the current itch NRS. Even if these technology-based approaches become the standard of measurement, they will certainly help us understand what we are measuring. And even better, the focus on how to develop meaningful end points around the improvement of itch will likely lead us to measure it more and drive the development of therapeutics that address the effect and consequences of this pernicious problem.

Historically, there have been limited data available on the management of psoriasis in pregnancy. The most comprehensive discussion of treatment guidelines is from 2012.¹ In the interim, many biologics have been approved for treating psoriasis, with slow accumulation of pregnancy safety data. The 2019 American Academy of Dermatology–National Psoriasis Foundation guidelines on biologics for psoriasis contain updated information but also highlight the paucity of pregnancy safety data.² This gap is in part a consequence of the exclusion and disenrollment of pregnant women from clinical trials.³ Additionally, lack of detection through registries contributes; pregnancy capture in registries is low compared to the expected number of pregnancies estimated from US Census data.⁴ Despite these shortcomings, psoriasis patients who are already pregnant or are considering becoming pregnant frequently are encountered in practice and may need treatment. This article reviews the evidence on commonly used treatments for psoriasis in pregnancy.

Background

For many patients, psoriasis improves during pregnancy^5,6 and becomes worse postpartum. In a prospective study, most patients reported improvement in pregnancy corresponding to a significant decrease in affected body surface area (P<.001) by 10 to 20 weeks’ gestation. Most patients also reported worsening of psoriasis postpartum; a significant increase in psoriatic body surface area (P=.001) was observed after delivery.⁷ Despite these findings, a considerable number of patients also experience stable disease or worsening of disease during pregnancy.

In addition to the maternal disease state, the issue of pregnancy outcomes is paramount. In the inflammatory bowel disease and rheumatology literature, it is established that uncontrolled disease is associated with poorer pregnancy outcomes.^8-10 Guidelines vary among societies on the use of biologics in pregnancy generally (eTable 1^1,2,9,11-24), but some societies recommend systemic agents to achieve disease control during pregnancy.^9,25

Assessing the potential interplay between disease severity and outcomes in pregnant women with psoriasis is further complicated by the slowly growing body of literature demonstrating that women with psoriasis have more comorbidities²⁶ and worse pregnancy outcomes.^27,28 Pregnant psoriasis patients are more likely to smoke, have depression, and be overweight or obese prior to pregnancy and are less likely to take prenatal vitamins.²⁶ They also have an increased risk for cesarean birth, gestational diabetes, gestational hypertension, and preeclampsia.²⁸ In contrast to these prior studies, a systematic review revealed no risk for adverse outcomes in pregnant women with psoriasis.²⁹

Assessment of Treatments for Psoriasis in Pregnancy

In light of these issues, treatment of psoriasis during pregnancy should be assessed from several vantage points. Of note, the US Food and Drug Administration changed its classification scheme in 2015 to a more narrative format called the Pregnancy and Lactation Labeling Rule.³⁰ Prior classifications, however, provide a reasonable starting point for categorizing the safety of drugs (Table³¹). Importantly, time of exposure to systemic agents also matters; first-trimester exposure is more likely to affect embryogenesis, whereas second- and third-trimester exposures are more prone to affect other aspects of fetal growth. eTable 2 provides data on the use of oral and topical medications to treat psoriasis in pregnancy.^1,8,22,32-45

Topical Agents
Topical steroids are largely understood to be reasonable treatment options, though consideration of potency, formulation, area of application, and use of occlusion is important.^1,46 Risk for orofacial cleft has been noted with first-trimester topical steroid exposure, though a 2015 Cochrane review update determined that the relative risk of this association was not significantly elevated.³²

The impact of topical calcipotriene and salicylic acid has not been studied in human pregnancies,¹ but systemic absorption can occur for both. There is potential for vitamin D toxicity with calcipotriene⁴⁶; consequently, use during pregnancy is not recommended.^1,46 Some authors recommend against topical salicylic acid in pregnancy; others report that limited exposure is permissible.⁴⁷ In fact, as salicylic acid commonly is found in over-the-counter acne products, many women of childbearing potential likely have quotidian exposure.

Preterm delivery and low birthweight have been reported with oral tacrolimus; however, risk with topical tacrolimus is thought to be low¹ because the molecular size likely prohibits notable absorption.⁴⁷ Evidence for the use of anthralin and coal tar also is scarce. First-trimester coal tar use should be avoided; subsequent use in pregnancy should be restricted given concern for adverse outcomes.¹

Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.¹ Phototherapy can exacerbate melasma⁴⁷ and decrease folate levels⁴⁸; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.⁴⁹ Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.¹

Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,¹ and systemic retinoids, which are teratogens, are contraindicated in pregnancy.^1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment⁵⁰ because alcohol intake prolongs the medication’s half-life.²²

Apremilast use is not documented in pregnant psoriasis patients⁵¹; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.⁵² Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.²²

Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.³⁸ A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.³⁹

Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.^53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.⁴² Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.⁴³ Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).

Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist²⁵ (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.⁸² Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.²

Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.⁸³

Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data²⁵ and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,^25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,⁸⁷ but given structural differences, transport of certolizumab and etanercept is substantially less.^88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.⁸⁸ There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).

Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.⁹⁰ This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.⁹¹

In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.⁹²

In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy⁸⁹ or exposed to neither agent.⁹³ A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.

Conclusion

Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.

Historically, there have been limited data available on the management of psoriasis in pregnancy. The most comprehensive discussion of treatment guidelines is from 2012.¹ In the interim, many biologics have been approved for treating psoriasis, with slow accumulation of pregnancy safety data. The 2019 American Academy of Dermatology–National Psoriasis Foundation guidelines on biologics for psoriasis contain updated information but also highlight the paucity of pregnancy safety data.² This gap is in part a consequence of the exclusion and disenrollment of pregnant women from clinical trials.³ Additionally, lack of detection through registries contributes; pregnancy capture in registries is low compared to the expected number of pregnancies estimated from US Census data.⁴ Despite these shortcomings, psoriasis patients who are already pregnant or are considering becoming pregnant frequently are encountered in practice and may need treatment. This article reviews the evidence on commonly used treatments for psoriasis in pregnancy.

Background

For many patients, psoriasis improves during pregnancy^5,6 and becomes worse postpartum. In a prospective study, most patients reported improvement in pregnancy corresponding to a significant decrease in affected body surface area (P<.001) by 10 to 20 weeks’ gestation. Most patients also reported worsening of psoriasis postpartum; a significant increase in psoriatic body surface area (P=.001) was observed after delivery.⁷ Despite these findings, a considerable number of patients also experience stable disease or worsening of disease during pregnancy.

In addition to the maternal disease state, the issue of pregnancy outcomes is paramount. In the inflammatory bowel disease and rheumatology literature, it is established that uncontrolled disease is associated with poorer pregnancy outcomes.^8-10 Guidelines vary among societies on the use of biologics in pregnancy generally (eTable 1^1,2,9,11-24), but some societies recommend systemic agents to achieve disease control during pregnancy.^9,25

Assessing the potential interplay between disease severity and outcomes in pregnant women with psoriasis is further complicated by the slowly growing body of literature demonstrating that women with psoriasis have more comorbidities²⁶ and worse pregnancy outcomes.^27,28 Pregnant psoriasis patients are more likely to smoke, have depression, and be overweight or obese prior to pregnancy and are less likely to take prenatal vitamins.²⁶ They also have an increased risk for cesarean birth, gestational diabetes, gestational hypertension, and preeclampsia.²⁸ In contrast to these prior studies, a systematic review revealed no risk for adverse outcomes in pregnant women with psoriasis.²⁹

Assessment of Treatments for Psoriasis in Pregnancy

In light of these issues, treatment of psoriasis during pregnancy should be assessed from several vantage points. Of note, the US Food and Drug Administration changed its classification scheme in 2015 to a more narrative format called the Pregnancy and Lactation Labeling Rule.³⁰ Prior classifications, however, provide a reasonable starting point for categorizing the safety of drugs (Table³¹). Importantly, time of exposure to systemic agents also matters; first-trimester exposure is more likely to affect embryogenesis, whereas second- and third-trimester exposures are more prone to affect other aspects of fetal growth. eTable 2 provides data on the use of oral and topical medications to treat psoriasis in pregnancy.^1,8,22,32-45

Topical Agents
Topical steroids are largely understood to be reasonable treatment options, though consideration of potency, formulation, area of application, and use of occlusion is important.^1,46 Risk for orofacial cleft has been noted with first-trimester topical steroid exposure, though a 2015 Cochrane review update determined that the relative risk of this association was not significantly elevated.³²

The impact of topical calcipotriene and salicylic acid has not been studied in human pregnancies,¹ but systemic absorption can occur for both. There is potential for vitamin D toxicity with calcipotriene⁴⁶; consequently, use during pregnancy is not recommended.^1,46 Some authors recommend against topical salicylic acid in pregnancy; others report that limited exposure is permissible.⁴⁷ In fact, as salicylic acid commonly is found in over-the-counter acne products, many women of childbearing potential likely have quotidian exposure.

Preterm delivery and low birthweight have been reported with oral tacrolimus; however, risk with topical tacrolimus is thought to be low¹ because the molecular size likely prohibits notable absorption.⁴⁷ Evidence for the use of anthralin and coal tar also is scarce. First-trimester coal tar use should be avoided; subsequent use in pregnancy should be restricted given concern for adverse outcomes.¹

Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.¹ Phototherapy can exacerbate melasma⁴⁷ and decrease folate levels⁴⁸; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.⁴⁹ Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.¹

Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,¹ and systemic retinoids, which are teratogens, are contraindicated in pregnancy.^1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment⁵⁰ because alcohol intake prolongs the medication’s half-life.²²

Apremilast use is not documented in pregnant psoriasis patients⁵¹; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.⁵² Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.²²

Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.³⁸ A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.³⁹

Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.^53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.⁴² Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.⁴³ Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).

Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist²⁵ (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.⁸² Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.²

Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.⁸³

Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data²⁵ and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,^25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,⁸⁷ but given structural differences, transport of certolizumab and etanercept is substantially less.^88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.⁸⁸ There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).

Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.⁹⁰ This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.⁹¹

In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.⁹²

In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy⁸⁹ or exposed to neither agent.⁹³ A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.

Conclusion

Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.

Historically, there have been limited data available on the management of psoriasis in pregnancy. The most comprehensive discussion of treatment guidelines is from 2012.¹ In the interim, many biologics have been approved for treating psoriasis, with slow accumulation of pregnancy safety data. The 2019 American Academy of Dermatology–National Psoriasis Foundation guidelines on biologics for psoriasis contain updated information but also highlight the paucity of pregnancy safety data.² This gap is in part a consequence of the exclusion and disenrollment of pregnant women from clinical trials.³ Additionally, lack of detection through registries contributes; pregnancy capture in registries is low compared to the expected number of pregnancies estimated from US Census data.⁴ Despite these shortcomings, psoriasis patients who are already pregnant or are considering becoming pregnant frequently are encountered in practice and may need treatment. This article reviews the evidence on commonly used treatments for psoriasis in pregnancy.

Background

For many patients, psoriasis improves during pregnancy^5,6 and becomes worse postpartum. In a prospective study, most patients reported improvement in pregnancy corresponding to a significant decrease in affected body surface area (P<.001) by 10 to 20 weeks’ gestation. Most patients also reported worsening of psoriasis postpartum; a significant increase in psoriatic body surface area (P=.001) was observed after delivery.⁷ Despite these findings, a considerable number of patients also experience stable disease or worsening of disease during pregnancy.

In addition to the maternal disease state, the issue of pregnancy outcomes is paramount. In the inflammatory bowel disease and rheumatology literature, it is established that uncontrolled disease is associated with poorer pregnancy outcomes.^8-10 Guidelines vary among societies on the use of biologics in pregnancy generally (eTable 1^1,2,9,11-24), but some societies recommend systemic agents to achieve disease control during pregnancy.^9,25

Assessing the potential interplay between disease severity and outcomes in pregnant women with psoriasis is further complicated by the slowly growing body of literature demonstrating that women with psoriasis have more comorbidities²⁶ and worse pregnancy outcomes.^27,28 Pregnant psoriasis patients are more likely to smoke, have depression, and be overweight or obese prior to pregnancy and are less likely to take prenatal vitamins.²⁶ They also have an increased risk for cesarean birth, gestational diabetes, gestational hypertension, and preeclampsia.²⁸ In contrast to these prior studies, a systematic review revealed no risk for adverse outcomes in pregnant women with psoriasis.²⁹

Assessment of Treatments for Psoriasis in Pregnancy

In light of these issues, treatment of psoriasis during pregnancy should be assessed from several vantage points. Of note, the US Food and Drug Administration changed its classification scheme in 2015 to a more narrative format called the Pregnancy and Lactation Labeling Rule.³⁰ Prior classifications, however, provide a reasonable starting point for categorizing the safety of drugs (Table³¹). Importantly, time of exposure to systemic agents also matters; first-trimester exposure is more likely to affect embryogenesis, whereas second- and third-trimester exposures are more prone to affect other aspects of fetal growth. eTable 2 provides data on the use of oral and topical medications to treat psoriasis in pregnancy.^1,8,22,32-45

Topical Agents
Topical steroids are largely understood to be reasonable treatment options, though consideration of potency, formulation, area of application, and use of occlusion is important.^1,46 Risk for orofacial cleft has been noted with first-trimester topical steroid exposure, though a 2015 Cochrane review update determined that the relative risk of this association was not significantly elevated.³²

The impact of topical calcipotriene and salicylic acid has not been studied in human pregnancies,¹ but systemic absorption can occur for both. There is potential for vitamin D toxicity with calcipotriene⁴⁶; consequently, use during pregnancy is not recommended.^1,46 Some authors recommend against topical salicylic acid in pregnancy; others report that limited exposure is permissible.⁴⁷ In fact, as salicylic acid commonly is found in over-the-counter acne products, many women of childbearing potential likely have quotidian exposure.

Preterm delivery and low birthweight have been reported with oral tacrolimus; however, risk with topical tacrolimus is thought to be low¹ because the molecular size likely prohibits notable absorption.⁴⁷ Evidence for the use of anthralin and coal tar also is scarce. First-trimester coal tar use should be avoided; subsequent use in pregnancy should be restricted given concern for adverse outcomes.¹

Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.¹ Phototherapy can exacerbate melasma⁴⁷ and decrease folate levels⁴⁸; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.⁴⁹ Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.¹

Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,¹ and systemic retinoids, which are teratogens, are contraindicated in pregnancy.^1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment⁵⁰ because alcohol intake prolongs the medication’s half-life.²²

Apremilast use is not documented in pregnant psoriasis patients⁵¹; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.⁵² Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.²²

Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.³⁸ A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.³⁹

Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.^53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.⁴² Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.⁴³ Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).

Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist²⁵ (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.⁸² Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.²

Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.⁸³

Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data²⁵ and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,^25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,⁸⁷ but given structural differences, transport of certolizumab and etanercept is substantially less.^88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.⁸⁸ There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).

Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.⁹⁰ This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.⁹¹

In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.⁹²

In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy⁸⁹ or exposed to neither agent.⁹³ A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.

Conclusion

Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.

Hidradenitis suppurativa (HS) is a common chronic inflammatory skin disease characterized by purulent subcutaneous nodules, papules, abscesses, and fistula tracts that lead to scarring and fibrosis. Lesions develop primarily in the axilla, groin, and other intertriginous and hair-bearing areas.

The natural history of the disease is characterized by periods of disease flare, followed by periods of disease quiescence. Patients might have weeks or months of low disease activity but frequently develop multiple exacerbating episodes over the course of weeks or months. The condition primarily presents in adolescent and peripubescent years, continuing throughout adulthood. Some evidence suggests a bimodal disease distribution, with a second peak of incidence in middle-aged adults. Women and men are affected equally; however, the disease can be phenotypically different in men and women.

Patients frequently present in emergency and inpatient settings for evaluation because of the pain and severity of HS flares as well as associated systemic symptoms. Inpatient and emergency department (ED) care are unique opportunities for dermatologic hospitalist and dermatologic consultative services to educate other physicians about the condition and initiate aggressive treatments that are frequently necessary to control HS flares. This article aims to address best methods for treating HS in these settings.

Pathophysiology

Although the exact pathophysiology of the condition is unknown, HS is thought to begin with follicular occlusion with downstream inflammation mediating neutrophilic activity and scarring. Hyperplasia of the infundibular epithelium is observed on histology, and the resulting occlusion, contained keratin, and follicular rupture initiate robust downstream inflammation.^1,2 Follicular occlusion might be initially androgen mediated³ or might occur in combination with friction⁴ and genetic or acquired factors involving Notch signaling. Although HS characteristically presents in areas of high apocrine density, apocrine glands are not thought to be the primary mediator of disease activity.⁵ IL-17, IL-23, tumor necrosis factor α, and IL-1β are implicated in the pathogenesis of HS, but it is unknown if these cytokines are the driving pathologic factor in HS or if they are merely secondary sequelae.⁶

Demographics and Prevalence in Hospitalized Patients

Although increasing treatment availability has brought more attention to HS, true prevalence is unknown. A prevalence of 1% has been reported in many European countries.⁷ Global prevalence has been more difficult to determine, with variable data suggesting a prevalence of 0.03% to 8%, depending on the population included.⁸ Most patients studied in a US-based claims database were aged 30 to 64 years, and the overall prevalence was 0.05%.⁹ Despite prevalence similar to psoriasis, utilization of high-cost emergency and inpatient admissions is notably higher among patients with HS. Recent claims data suggest that HS patients utilize the ED at a rate 3 times higher than psoriasis patients and are admitted as inpatients at a rate 5 times higher.¹⁰ Similar data suggest an associated increased cost of care for patients with HS vs other conditions, such as psoriasis, due to frequent ED and inpatient stays.¹¹ Although HS frequently presents in the inpatient and emergency settings, there is little literature on best methods for managing patients in these settings.

Pearls for Inpatient and Emergency Evaluation and Management

Initial Evaluation
When dermatologic consultative services are asked to evaluate patients with HS, preliminary evaluation should reflect the acuity of the patient. Vital signs and toxicity should be reviewed to ensure that there is no evidence of severe infection necessitating critical or acute care.

History
History-taking should reflect assessment of the patient’s baseline disease, including date of initial onset; exacerbating factors, such as friction, smoking, pregnancy, and menses; and the current history of the patient’s flare. A history of antibiotics, immunosuppression, topical therapy, antiandrogen therapy, and vitamin A analog therapy also should be reviewed. If an initial diagnosis is made in the ED or inpatient setting, a family and personal history should focus on specific risk factors and disease associations, including inflammatory bowel disease,¹² pilonidal cysts,¹³ polycystic ovary syndrome,¹⁴ and metabolic syndrome.¹⁵

Physical Examination
As with all dermatologic consultations, a full-body skin examination, with special attention to the axilla, inframammary skin, groin, buttocks, and perineum, should be undertaken. In addition to these common areas of disease progression, examination should focus on atypical sites for disease manifestation, including the posterior auricular scalp, skin folds in the pannus and back, and the beard area in men. Evaluation of axillary and gluteal hair should note features of folliculitis and hair removal, which can exacerbate HS. Examination also should include an investigation of cutaneous manifestations of comorbid conditions, including acanthosis nigricans, contiguous or metastatic cutaneous Crohn disease, erythema nodosum, and pilonidal cysts. Caution should be exercised when diagnosing pilonidal cysts, as isolated or evolving HS in the gluteal cleft often is misdiagnosed as a pilonidal cyst.

Laboratory Evaluation
Testing often is misleading in patients with HS, especially in the acute setting, because the condition is a chronic inflammatory process. The C-reactive protein level as well as the absolute white blood cell and neutrophil counts often are elevated, even in the absence of acute infection.¹⁶ In fact, although patients often are treated with intravenous antibiotics by inpatient and emergency teams in the setting of these 3 laboratory abnormalities, these findings often reflect disease activity, not frank infection. Fever, especially low-grade fever, also can reflect ongoing disease activity. Thrombocytosis and anemia also are anecdotally common, though these findings have not been reported specifically in the literature.

Bacterial Cultures
The role of lesional and perilesional bacterial cultures is controversial in HS. Prior studies have demonstrated that biofilm formation may be associated with the chronic inflammation seen in HS.¹⁷ However, most data to date suggest that infection is not the primary driver of HS disease flares, as demonstrated by the frequency of sterile cultures and the variable response of the disease to penicillin and related antibiotics.¹⁸

Imaging
Ultrasonography and magnetic resonance imaging can be conducted if there is concern about deeper abscesses that are not apparent on examination. When interpreted by nondermatologic practitioners, however, the findings of these modalities can result in unnecessary surgical intervention, given the concern for development of infectious abscess.¹⁹

Diagnosis
Many patients with HS experience a notable delay in time to diagnosis, living with symptoms for 7 years on average prior to being given a name for their condition.²⁰ Often, patients seek ED care at initial presentation because lesions can present quickly and are associated with remarkable pain. Inpatient dermatologic evaluation can provide patients with definitive diagnosis, appropriate counseling that provides an overview of the natural history of the disease, lifestyle recommendations, and expedited connection to outpatient longitudinal care.

Diagnosis is made clinically by assessment for typical lesions, such as painful or tender papules, nodules, or abscesses in the axillae, inframammary region, groin, thighs, and perineal and perianal regions. Cordlike scarring often is seen in the absence of active inflammatory lesions.²¹ Double-headed open comedones and prominent follicular occlusion are seen in some phenotypes but are not required for diagnosis.²²

Multiple scoring modalities are in use²³; the Hurley staging system, initially developed for surgical staging, has become a commonly used method in the clinical setting²⁴:

• Hurley stage I: isolated nodules or abscesses;

• Hurley stage II: widely separate lesions and sinus tracts or scarring are suggestive; and

• Hurley stage III: multiple lesions with near-diffuse involvement and formation of sinus tracts and scarring.

Other scoring modalities, such as the Hidradenitis Suppurativa Clinical Response (HiSCR), are more commonly used in the clinical trial setting and quantitatively capture lesion count improvement while the patient is being treated.²⁵

Treatment
Evaluation in the ED might necessitate recommendations for inpatient admission. Dermatologic consultation can be helpful in providing ED physicians with context for interpretation of laboratory results and clinical findings. Specifically, dermatologic evaluation can help differentiate presentations consistent with a primary infection from a more common presentation of HS flaring and associated bacterial colonization. Indications for inpatient admission are severe pain; concern for systemic infection, including high fever or sepsis; and need for surgical intervention. Patients with severe disease who do not have a longitudinal care plan or who lack the ability to care for lesions at home also are candidates for inpatient admission, where they can receive more intensive nursing and wound care as well as outpatient logistical management.

Acute care should be aimed at treatments that work quickly and aggressively and have both anti-inflammatory and antimicrobial effects. Severe flares require aggressive initial treatment to ensure more long-term remission. Adalimumab, maintained at 40 mg/wk after a loading dose, is the mainstay of evidence-based treatment for moderate to severe HS in patients 12 years or older; however, this treatment might not be easy to initiate in the inpatient setting because of its cost and availability and the fact that it is not as fast acting as other therapies.²⁶ For patients with severe disease flares, prednisone,²⁷ infliximab,²⁸ or cyclosporine²⁹ can be used in combination with antimicrobial therapy in the inpatient setting to quickly control active flaring. Intravenous antimicrobial therapy might be necessary in severe disease and should include coverage of gram-positive³⁰ and anaerobic organisms.³¹

Although management of acute flares is critical, especially for hospitalized patients, initiating longitudinal treatment modalities while the patient is an inpatient will help prevent future readmissions, facilitate better outcomes, and enable longer periods of disease-free progression. Specific treatments, stratified by disease severity, are listed in the Table.

Lastly, appropriate postdischarge maintenance therapy also can be initiated during the inpatient stay, including maintenance antibiotic therapy, spironolactone³² for female patients, and acitretin³³ for comedonal-predominant patients.

Final Thoughts

Hidradenitis suppurativa is a common dermatologic condition that frequently presents in emergency and inpatient settings, given its association with painful and acutely indurated lesions that often appear concerning for infection. Elevated inflammatory markers and fever are common in HS and are not necessarily suggestive of infection. As such, while antibiotics may be part of acute management of HS, care also should address the inflammatory component of the disease. Longitudinal outpatient care coordination with a dermatologist and primary care physician is imperative for limiting ED and inpatient care utilization.

Hidradenitis suppurativa (HS) is a common chronic inflammatory skin disease characterized by purulent subcutaneous nodules, papules, abscesses, and fistula tracts that lead to scarring and fibrosis. Lesions develop primarily in the axilla, groin, and other intertriginous and hair-bearing areas.

The natural history of the disease is characterized by periods of disease flare, followed by periods of disease quiescence. Patients might have weeks or months of low disease activity but frequently develop multiple exacerbating episodes over the course of weeks or months. The condition primarily presents in adolescent and peripubescent years, continuing throughout adulthood. Some evidence suggests a bimodal disease distribution, with a second peak of incidence in middle-aged adults. Women and men are affected equally; however, the disease can be phenotypically different in men and women.

Patients frequently present in emergency and inpatient settings for evaluation because of the pain and severity of HS flares as well as associated systemic symptoms. Inpatient and emergency department (ED) care are unique opportunities for dermatologic hospitalist and dermatologic consultative services to educate other physicians about the condition and initiate aggressive treatments that are frequently necessary to control HS flares. This article aims to address best methods for treating HS in these settings.

Pathophysiology

Although the exact pathophysiology of the condition is unknown, HS is thought to begin with follicular occlusion with downstream inflammation mediating neutrophilic activity and scarring. Hyperplasia of the infundibular epithelium is observed on histology, and the resulting occlusion, contained keratin, and follicular rupture initiate robust downstream inflammation.^1,2 Follicular occlusion might be initially androgen mediated³ or might occur in combination with friction⁴ and genetic or acquired factors involving Notch signaling. Although HS characteristically presents in areas of high apocrine density, apocrine glands are not thought to be the primary mediator of disease activity.⁵ IL-17, IL-23, tumor necrosis factor α, and IL-1β are implicated in the pathogenesis of HS, but it is unknown if these cytokines are the driving pathologic factor in HS or if they are merely secondary sequelae.⁶

Demographics and Prevalence in Hospitalized Patients

Although increasing treatment availability has brought more attention to HS, true prevalence is unknown. A prevalence of 1% has been reported in many European countries.⁷ Global prevalence has been more difficult to determine, with variable data suggesting a prevalence of 0.03% to 8%, depending on the population included.⁸ Most patients studied in a US-based claims database were aged 30 to 64 years, and the overall prevalence was 0.05%.⁹ Despite prevalence similar to psoriasis, utilization of high-cost emergency and inpatient admissions is notably higher among patients with HS. Recent claims data suggest that HS patients utilize the ED at a rate 3 times higher than psoriasis patients and are admitted as inpatients at a rate 5 times higher.¹⁰ Similar data suggest an associated increased cost of care for patients with HS vs other conditions, such as psoriasis, due to frequent ED and inpatient stays.¹¹ Although HS frequently presents in the inpatient and emergency settings, there is little literature on best methods for managing patients in these settings.

Pearls for Inpatient and Emergency Evaluation and Management

Initial Evaluation
When dermatologic consultative services are asked to evaluate patients with HS, preliminary evaluation should reflect the acuity of the patient. Vital signs and toxicity should be reviewed to ensure that there is no evidence of severe infection necessitating critical or acute care.

History
History-taking should reflect assessment of the patient’s baseline disease, including date of initial onset; exacerbating factors, such as friction, smoking, pregnancy, and menses; and the current history of the patient’s flare. A history of antibiotics, immunosuppression, topical therapy, antiandrogen therapy, and vitamin A analog therapy also should be reviewed. If an initial diagnosis is made in the ED or inpatient setting, a family and personal history should focus on specific risk factors and disease associations, including inflammatory bowel disease,¹² pilonidal cysts,¹³ polycystic ovary syndrome,¹⁴ and metabolic syndrome.¹⁵

Physical Examination
As with all dermatologic consultations, a full-body skin examination, with special attention to the axilla, inframammary skin, groin, buttocks, and perineum, should be undertaken. In addition to these common areas of disease progression, examination should focus on atypical sites for disease manifestation, including the posterior auricular scalp, skin folds in the pannus and back, and the beard area in men. Evaluation of axillary and gluteal hair should note features of folliculitis and hair removal, which can exacerbate HS. Examination also should include an investigation of cutaneous manifestations of comorbid conditions, including acanthosis nigricans, contiguous or metastatic cutaneous Crohn disease, erythema nodosum, and pilonidal cysts. Caution should be exercised when diagnosing pilonidal cysts, as isolated or evolving HS in the gluteal cleft often is misdiagnosed as a pilonidal cyst.

Laboratory Evaluation
Testing often is misleading in patients with HS, especially in the acute setting, because the condition is a chronic inflammatory process. The C-reactive protein level as well as the absolute white blood cell and neutrophil counts often are elevated, even in the absence of acute infection.¹⁶ In fact, although patients often are treated with intravenous antibiotics by inpatient and emergency teams in the setting of these 3 laboratory abnormalities, these findings often reflect disease activity, not frank infection. Fever, especially low-grade fever, also can reflect ongoing disease activity. Thrombocytosis and anemia also are anecdotally common, though these findings have not been reported specifically in the literature.

Bacterial Cultures
The role of lesional and perilesional bacterial cultures is controversial in HS. Prior studies have demonstrated that biofilm formation may be associated with the chronic inflammation seen in HS.¹⁷ However, most data to date suggest that infection is not the primary driver of HS disease flares, as demonstrated by the frequency of sterile cultures and the variable response of the disease to penicillin and related antibiotics.¹⁸

Imaging
Ultrasonography and magnetic resonance imaging can be conducted if there is concern about deeper abscesses that are not apparent on examination. When interpreted by nondermatologic practitioners, however, the findings of these modalities can result in unnecessary surgical intervention, given the concern for development of infectious abscess.¹⁹

Diagnosis
Many patients with HS experience a notable delay in time to diagnosis, living with symptoms for 7 years on average prior to being given a name for their condition.²⁰ Often, patients seek ED care at initial presentation because lesions can present quickly and are associated with remarkable pain. Inpatient dermatologic evaluation can provide patients with definitive diagnosis, appropriate counseling that provides an overview of the natural history of the disease, lifestyle recommendations, and expedited connection to outpatient longitudinal care.

Diagnosis is made clinically by assessment for typical lesions, such as painful or tender papules, nodules, or abscesses in the axillae, inframammary region, groin, thighs, and perineal and perianal regions. Cordlike scarring often is seen in the absence of active inflammatory lesions.²¹ Double-headed open comedones and prominent follicular occlusion are seen in some phenotypes but are not required for diagnosis.²²

Multiple scoring modalities are in use²³; the Hurley staging system, initially developed for surgical staging, has become a commonly used method in the clinical setting²⁴:

• Hurley stage I: isolated nodules or abscesses;

• Hurley stage II: widely separate lesions and sinus tracts or scarring are suggestive; and

• Hurley stage III: multiple lesions with near-diffuse involvement and formation of sinus tracts and scarring.

Other scoring modalities, such as the Hidradenitis Suppurativa Clinical Response (HiSCR), are more commonly used in the clinical trial setting and quantitatively capture lesion count improvement while the patient is being treated.²⁵

Treatment
Evaluation in the ED might necessitate recommendations for inpatient admission. Dermatologic consultation can be helpful in providing ED physicians with context for interpretation of laboratory results and clinical findings. Specifically, dermatologic evaluation can help differentiate presentations consistent with a primary infection from a more common presentation of HS flaring and associated bacterial colonization. Indications for inpatient admission are severe pain; concern for systemic infection, including high fever or sepsis; and need for surgical intervention. Patients with severe disease who do not have a longitudinal care plan or who lack the ability to care for lesions at home also are candidates for inpatient admission, where they can receive more intensive nursing and wound care as well as outpatient logistical management.

Acute care should be aimed at treatments that work quickly and aggressively and have both anti-inflammatory and antimicrobial effects. Severe flares require aggressive initial treatment to ensure more long-term remission. Adalimumab, maintained at 40 mg/wk after a loading dose, is the mainstay of evidence-based treatment for moderate to severe HS in patients 12 years or older; however, this treatment might not be easy to initiate in the inpatient setting because of its cost and availability and the fact that it is not as fast acting as other therapies.²⁶ For patients with severe disease flares, prednisone,²⁷ infliximab,²⁸ or cyclosporine²⁹ can be used in combination with antimicrobial therapy in the inpatient setting to quickly control active flaring. Intravenous antimicrobial therapy might be necessary in severe disease and should include coverage of gram-positive³⁰ and anaerobic organisms.³¹

Although management of acute flares is critical, especially for hospitalized patients, initiating longitudinal treatment modalities while the patient is an inpatient will help prevent future readmissions, facilitate better outcomes, and enable longer periods of disease-free progression. Specific treatments, stratified by disease severity, are listed in the Table.

Lastly, appropriate postdischarge maintenance therapy also can be initiated during the inpatient stay, including maintenance antibiotic therapy, spironolactone³² for female patients, and acitretin³³ for comedonal-predominant patients.

Final Thoughts

Hidradenitis suppurativa is a common dermatologic condition that frequently presents in emergency and inpatient settings, given its association with painful and acutely indurated lesions that often appear concerning for infection. Elevated inflammatory markers and fever are common in HS and are not necessarily suggestive of infection. As such, while antibiotics may be part of acute management of HS, care also should address the inflammatory component of the disease. Longitudinal outpatient care coordination with a dermatologist and primary care physician is imperative for limiting ED and inpatient care utilization.

Hidradenitis suppurativa (HS) is a common chronic inflammatory skin disease characterized by purulent subcutaneous nodules, papules, abscesses, and fistula tracts that lead to scarring and fibrosis. Lesions develop primarily in the axilla, groin, and other intertriginous and hair-bearing areas.

The natural history of the disease is characterized by periods of disease flare, followed by periods of disease quiescence. Patients might have weeks or months of low disease activity but frequently develop multiple exacerbating episodes over the course of weeks or months. The condition primarily presents in adolescent and peripubescent years, continuing throughout adulthood. Some evidence suggests a bimodal disease distribution, with a second peak of incidence in middle-aged adults. Women and men are affected equally; however, the disease can be phenotypically different in men and women.

Patients frequently present in emergency and inpatient settings for evaluation because of the pain and severity of HS flares as well as associated systemic symptoms. Inpatient and emergency department (ED) care are unique opportunities for dermatologic hospitalist and dermatologic consultative services to educate other physicians about the condition and initiate aggressive treatments that are frequently necessary to control HS flares. This article aims to address best methods for treating HS in these settings.

Pathophysiology

Although the exact pathophysiology of the condition is unknown, HS is thought to begin with follicular occlusion with downstream inflammation mediating neutrophilic activity and scarring. Hyperplasia of the infundibular epithelium is observed on histology, and the resulting occlusion, contained keratin, and follicular rupture initiate robust downstream inflammation.^1,2 Follicular occlusion might be initially androgen mediated³ or might occur in combination with friction⁴ and genetic or acquired factors involving Notch signaling. Although HS characteristically presents in areas of high apocrine density, apocrine glands are not thought to be the primary mediator of disease activity.⁵ IL-17, IL-23, tumor necrosis factor α, and IL-1β are implicated in the pathogenesis of HS, but it is unknown if these cytokines are the driving pathologic factor in HS or if they are merely secondary sequelae.⁶

Demographics and Prevalence in Hospitalized Patients

Although increasing treatment availability has brought more attention to HS, true prevalence is unknown. A prevalence of 1% has been reported in many European countries.⁷ Global prevalence has been more difficult to determine, with variable data suggesting a prevalence of 0.03% to 8%, depending on the population included.⁸ Most patients studied in a US-based claims database were aged 30 to 64 years, and the overall prevalence was 0.05%.⁹ Despite prevalence similar to psoriasis, utilization of high-cost emergency and inpatient admissions is notably higher among patients with HS. Recent claims data suggest that HS patients utilize the ED at a rate 3 times higher than psoriasis patients and are admitted as inpatients at a rate 5 times higher.¹⁰ Similar data suggest an associated increased cost of care for patients with HS vs other conditions, such as psoriasis, due to frequent ED and inpatient stays.¹¹ Although HS frequently presents in the inpatient and emergency settings, there is little literature on best methods for managing patients in these settings.

Pearls for Inpatient and Emergency Evaluation and Management

Initial Evaluation
When dermatologic consultative services are asked to evaluate patients with HS, preliminary evaluation should reflect the acuity of the patient. Vital signs and toxicity should be reviewed to ensure that there is no evidence of severe infection necessitating critical or acute care.

History
History-taking should reflect assessment of the patient’s baseline disease, including date of initial onset; exacerbating factors, such as friction, smoking, pregnancy, and menses; and the current history of the patient’s flare. A history of antibiotics, immunosuppression, topical therapy, antiandrogen therapy, and vitamin A analog therapy also should be reviewed. If an initial diagnosis is made in the ED or inpatient setting, a family and personal history should focus on specific risk factors and disease associations, including inflammatory bowel disease,¹² pilonidal cysts,¹³ polycystic ovary syndrome,¹⁴ and metabolic syndrome.¹⁵

Physical Examination
As with all dermatologic consultations, a full-body skin examination, with special attention to the axilla, inframammary skin, groin, buttocks, and perineum, should be undertaken. In addition to these common areas of disease progression, examination should focus on atypical sites for disease manifestation, including the posterior auricular scalp, skin folds in the pannus and back, and the beard area in men. Evaluation of axillary and gluteal hair should note features of folliculitis and hair removal, which can exacerbate HS. Examination also should include an investigation of cutaneous manifestations of comorbid conditions, including acanthosis nigricans, contiguous or metastatic cutaneous Crohn disease, erythema nodosum, and pilonidal cysts. Caution should be exercised when diagnosing pilonidal cysts, as isolated or evolving HS in the gluteal cleft often is misdiagnosed as a pilonidal cyst.

Laboratory Evaluation
Testing often is misleading in patients with HS, especially in the acute setting, because the condition is a chronic inflammatory process. The C-reactive protein level as well as the absolute white blood cell and neutrophil counts often are elevated, even in the absence of acute infection.¹⁶ In fact, although patients often are treated with intravenous antibiotics by inpatient and emergency teams in the setting of these 3 laboratory abnormalities, these findings often reflect disease activity, not frank infection. Fever, especially low-grade fever, also can reflect ongoing disease activity. Thrombocytosis and anemia also are anecdotally common, though these findings have not been reported specifically in the literature.

Bacterial Cultures
The role of lesional and perilesional bacterial cultures is controversial in HS. Prior studies have demonstrated that biofilm formation may be associated with the chronic inflammation seen in HS.¹⁷ However, most data to date suggest that infection is not the primary driver of HS disease flares, as demonstrated by the frequency of sterile cultures and the variable response of the disease to penicillin and related antibiotics.¹⁸

Imaging
Ultrasonography and magnetic resonance imaging can be conducted if there is concern about deeper abscesses that are not apparent on examination. When interpreted by nondermatologic practitioners, however, the findings of these modalities can result in unnecessary surgical intervention, given the concern for development of infectious abscess.¹⁹

Diagnosis
Many patients with HS experience a notable delay in time to diagnosis, living with symptoms for 7 years on average prior to being given a name for their condition.²⁰ Often, patients seek ED care at initial presentation because lesions can present quickly and are associated with remarkable pain. Inpatient dermatologic evaluation can provide patients with definitive diagnosis, appropriate counseling that provides an overview of the natural history of the disease, lifestyle recommendations, and expedited connection to outpatient longitudinal care.

Diagnosis is made clinically by assessment for typical lesions, such as painful or tender papules, nodules, or abscesses in the axillae, inframammary region, groin, thighs, and perineal and perianal regions. Cordlike scarring often is seen in the absence of active inflammatory lesions.²¹ Double-headed open comedones and prominent follicular occlusion are seen in some phenotypes but are not required for diagnosis.²²

Multiple scoring modalities are in use²³; the Hurley staging system, initially developed for surgical staging, has become a commonly used method in the clinical setting²⁴:

• Hurley stage I: isolated nodules or abscesses;

• Hurley stage II: widely separate lesions and sinus tracts or scarring are suggestive; and

• Hurley stage III: multiple lesions with near-diffuse involvement and formation of sinus tracts and scarring.

Other scoring modalities, such as the Hidradenitis Suppurativa Clinical Response (HiSCR), are more commonly used in the clinical trial setting and quantitatively capture lesion count improvement while the patient is being treated.²⁵

Treatment
Evaluation in the ED might necessitate recommendations for inpatient admission. Dermatologic consultation can be helpful in providing ED physicians with context for interpretation of laboratory results and clinical findings. Specifically, dermatologic evaluation can help differentiate presentations consistent with a primary infection from a more common presentation of HS flaring and associated bacterial colonization. Indications for inpatient admission are severe pain; concern for systemic infection, including high fever or sepsis; and need for surgical intervention. Patients with severe disease who do not have a longitudinal care plan or who lack the ability to care for lesions at home also are candidates for inpatient admission, where they can receive more intensive nursing and wound care as well as outpatient logistical management.

Acute care should be aimed at treatments that work quickly and aggressively and have both anti-inflammatory and antimicrobial effects. Severe flares require aggressive initial treatment to ensure more long-term remission. Adalimumab, maintained at 40 mg/wk after a loading dose, is the mainstay of evidence-based treatment for moderate to severe HS in patients 12 years or older; however, this treatment might not be easy to initiate in the inpatient setting because of its cost and availability and the fact that it is not as fast acting as other therapies.²⁶ For patients with severe disease flares, prednisone,²⁷ infliximab,²⁸ or cyclosporine²⁹ can be used in combination with antimicrobial therapy in the inpatient setting to quickly control active flaring. Intravenous antimicrobial therapy might be necessary in severe disease and should include coverage of gram-positive³⁰ and anaerobic organisms.³¹

Although management of acute flares is critical, especially for hospitalized patients, initiating longitudinal treatment modalities while the patient is an inpatient will help prevent future readmissions, facilitate better outcomes, and enable longer periods of disease-free progression. Specific treatments, stratified by disease severity, are listed in the Table.

Lastly, appropriate postdischarge maintenance therapy also can be initiated during the inpatient stay, including maintenance antibiotic therapy, spironolactone³² for female patients, and acitretin³³ for comedonal-predominant patients.

Final Thoughts

Hidradenitis suppurativa is a common dermatologic condition that frequently presents in emergency and inpatient settings, given its association with painful and acutely indurated lesions that often appear concerning for infection. Elevated inflammatory markers and fever are common in HS and are not necessarily suggestive of infection. As such, while antibiotics may be part of acute management of HS, care also should address the inflammatory component of the disease. Longitudinal outpatient care coordination with a dermatologist and primary care physician is imperative for limiting ED and inpatient care utilization.

Psoriasis is a chronic autoinflammatory disorder affecting approximately 2% to 4% of the Western population.¹ While there is no absolute cure for psoriasis, novel therapies allow for substantial reduction in symptoms and considerable improvement in quality of life (QoL). In the past few years, multiple treatment guidelines (recommendations based on evidence-based literature reviews) and consensus statements (a set of declarations determined and voted on by a panel of experts in the field) have been developed to guide physicians worldwide in treating psoriasis in the clinical setting (eTable).^2-10

Because psoriasis is a complex disease with multiple comorbidities, applicability of these guidelines may be limited. Although some basic treatment algorithms exist, patient preference, disease severity, and other variables including comorbidities (eg, psoriatic arthritis [PsA], risk of major cardiac events, inflammatory bowel disease [IBD]), history of nonmelanoma skin cancer (NMSC), pregnancy and lactation, and specific contraindications to therapy (eg, renal failure, liver disease, active malignancy) should be considered. In this article, we summarize common themes across existing guidelines and consensus statements for the treatment of psoriasis and highlight areas where there is consistent agreement or lack of sufficient information.

Disease Severity and Treatment Outcomes

There currently are no consensus definitions for mild, moderate, and severe psoriasis, but several consensus statements have attempted to standardize grading systems based on objective values, such as body surface area (BSA) and psoriasis area and severity index (PASI)(a scoring system used to grade the degree of redness, thickness, and scaling of psoriasis plaques), as well as subjective QoL measures.^2,6 Although classification of disease severity varies, mild psoriasis generally is characterized as disease that can be managed with local and topical therapy, and moderate to severe psoriasis typically warrants consideration for escalated treatment with phototherapy or systemic agents.

Most definitions of disease severity in psoriasis reference 5% to 10% BSA involvement as a cutoff that should trigger consideration of systemic treatment; however, these criteria could result in undertreatment of patients with substantial disease. For example, patients who have limited BSA involvement but whose disease has a considerable impact on QoL, as well as those who have debilitating disease in localized areas (eg, palms, soles, scalp, nails) or substantial joint involvement may also be appropriate candidates for systemic treatment.^5,8

Once therapy is initiated, patients should be evaluated for appropriate treatment response at dedicated intervals. While the time to maximum therapeutic benefit depends on the agent of choice, European guidelines recommend that patients be evaluated after an induction phase (typically 16–24 weeks) and define treatment success as either (1) at least 75% improvement in PASI or (2) at least 50% improvement in PASI and a Dermatology Quality of Life Index (DLQI) score of 5 or lower.⁶

Alternatively, the National Psoriasis Foundation (NPF) recommended BSA as the preferred outcome measure in a recent consensus statement and concluded that an outcome of 3% or less BSA involvement or improvement in BSA of 75% or more is considered a desirable treatment response.⁹ Additionally, the Medicare Merit-based Incentive Payment System (MIPS) guidelines for successful systemic treatment response include at least 1 of the following: (1) physician global assessment score of 2 or lower, (2) BSA involvement of less than 3%, (3) PASI score lower than 3, or (4) DLQI score of 5 or lower.¹⁰

Although an array of outcome measures have been utilized in clinical trials and proposed in psoriasis guidelines and consensus statements, BSA is typically a manageable measure of treatment response in a clinical setting; however, DLQI should also be assessed if possible, particularly in patients with debilitating localized disease.⁹

Treatment Options

Because topical treatment regimens can be arduous and typically do not result in sustained clearance, patient expectations should be ascertained prior to initiation of therapy. Topical corticosteroids often can be used as monotherapy in patients with mild psoriasis.³ Topical vitamin D analogues and retinoids also can be effective; however, combined use of these agents with topical steroids should be considered to increase efficacy, and combination formulations can be prescribed to simplify application and improve adherence.

Treatment with UVB or psoralen plus UVA phototherapy is recommended for patients with moderate to severe psoriasis as well as in those who have had minimal response to topical therapy.⁴ Targeted phototherapy with an excimer laser can be used in patients with BSA involvement of less than 10%.

Methotrexate (MTX), cyclosporine, and acitretin are the most commonly prescribed systemic medications for severe psoriasis in the United States.⁵ Despite the risk for hepatotoxicity, MTX appears to have the best combined safety and efficacy profile in terms of serious adverse events compared to other systemic agents.¹¹ Guidelines for MTX monitoring, especially with regard to when to do a liver biopsy, have been substantially liberalized over time, and the recommended interval for biopsy has been extended by years; biopsy was previously recommended after a cumulative MTX dose of 1 to 1.5 g, but guidelines now suggest biopsy after 3.5 to 4 g in low-risk patients.⁵ While abnormally elevated liver function tests during treatment with MTX may necessitate liver biopsy, the use of transient elastography and a panel of serum biomarkers for liver function also can be used to monitor noninvasively for hepatotoxicity before biopsy is considered; these recommendations are likely to be incorporated into newer guidelines in development.¹² Methotrexate has demonstrated safety and increased efficacy when used in combination with biologic agents such as adalimumab, etanercept, infliximab, and secukinumab⁷ and has been studied in combination with many biologics indicated for PsA.¹³

Due to a considerable risk of glomerulosclerosis, cyclosporine is approved for a maximum of 1 year of continuous treatment of psoriasis in the United States and2 years in Europe.^5,7 Cyclosporine is best used as induction therapy in psoriasis patients with severe disease who are seeking faster abatement of symptoms.

Acitretin is another systemic treatment option, although efficacy of this agent is dose dependent. Higher dosing often is limited due to lower tolerability.⁵

Given that many insurance formularies primarily cover traditional systemic therapies and that MTX and phototherapy are generally well tolerated and cost effective, patients may need to be treated with traditional agents before escalating to biologics. Prior to starting treatment with any biologic, patients should typically be screened for tuberculosis (TB), human immunodeficiency virus infection, and immunization for, exposure to, and/or infection with hepatitis B and C virus, and any other active infections. In patients who do not demonstrate hepatitis immunity, the hepatitis B vaccine should be administered prior to starting treatment with a biologic.¹⁴ In psoriasis patients with latent TB, 2 months of treatment should be completed before initiating biologic therapy⁸; once a biologic has been initiated, all patients should be screened annually for TB.

European guidelines for biologic treatment recommend that complete blood count and liver and renal function be evaluated at baseline, at months 1 and 3 of treatment, and then every 3 to 6 months thereafter while on the biologic agent.⁷ These recommendations are more stringent than those indicated in regulatory labeling and, based on the continual accumulation of data regarding the safety of these agents, some investigators have argued that laboratory testing might not be necessary at all.¹⁵

Treatment in Special Populations

Psoriasis patients often present with comorbidities or a complicated medical history, which can make it challenging to decide which therapy is most suitable. Patients with comorbid diseases (eg, PsA, risk of major cardiac event, IBD) or a history of NMSC and those who are pregnant or are lactating require special considerations to ensure treatment safety and efficacy.

Tumor necrosis factor α (TNF-α) and IL-17 inhibitors are used in the treatment of joint disorders and should be considered in patients with PsA. IL-23/IL-12 inhibition appears to have less benefit in patients with PsA, but studies on IL-23 inhibition (p19 antibodies) alone are ongoing.¹⁶ It has been reported that TNF-α inhibition may be beneficial in patients at risk for major cardiac events.^8,17 In patients with IBD, IL-17 inhibitors should be avoided because they may exacerbate the condition; however, TNF-α and IL-23/IL-12 inhibition have shown to be safe in patients with IBD and many agents in these classes are approved by the US Food and Drug Administration for use in this population.^18,19

Although biologics may increase the risk of developing NMSC²⁰ and should generally be avoided in patients with any active malignancy, specific guidelines for screening and initiation of treatment in patients with a history of cancer are not clearly outlined. Prior to initiating systemic therapy in any patient, a careful medical history should be obtained. These agents often are not prescribed in patients with a history of cancer until remission has been established for at least 5 years, with the exception of patients with a history of treated NMSC.⁸ Annual skin monitoring for NMSC should be undertaken for psoriasis patients on most immunomodulating systemic therapies.

Recommendations for biologic treatment in psoriasis patients who are pregnant or lactating also are limited. European guidelines have noted pregnancy as an absolute contraindication to treatment with biologics,⁷but the regulatory guidance has recently changed for some agents, so this recommendation also may evolve.²¹ British⁸ and US⁵ guidelines do not consider pregnancy a contraindication for treatment with biologics.

Information on the safety of TNF-α antagonists during pregnancy comes primarily from use in patients with IBD and rheumatologic disease. To date, reports on the incidence of congenital malformations have been generally reassuring. Because IgG antibodies are actively transferred across the placenta in the late-second or the third trimesters, neonates born to mothers on biologic treatments may have high levels of some biologic drugs at birth. As a result, live vaccination should be avoided in neonates whose mothers were treated with IgG-based biologics.

Changing Treatment Agents

Patients may need to stop and change treatment agents due to ineffectiveness, personal preference, or worsening disease. When transitioning from any systemic or biologic agent to another (other than MTX), the British Association of Dermatologists recommends a washout period of at least 1 month before initiating a new therapy.⁸ Most guidelines do not define parameters for therapy escalation when patients fail multiple systemic agents, so physicians should use clinical judgment along with consideration of patient preference and comorbidity profile to ascertain which agent is most appropriate.

Conclusion

Keeping psoriasis treatment guidelines updated can be difficult, especially as new therapeutic options for psoriasis and treatment regimens rapidly evolve. Regulatory recommendations also vary worldwide, but most guidelines are reasonably consistent without being overly prescriptive, appropriately allowing for flexibility for application in clinical practice. Nonetheless, physicians should keep in mind new or changing guidelines while tailoring psoriasis treatment recommendations to best suit their individual patients.

Psoriasis is a chronic autoinflammatory disorder affecting approximately 2% to 4% of the Western population.¹ While there is no absolute cure for psoriasis, novel therapies allow for substantial reduction in symptoms and considerable improvement in quality of life (QoL). In the past few years, multiple treatment guidelines (recommendations based on evidence-based literature reviews) and consensus statements (a set of declarations determined and voted on by a panel of experts in the field) have been developed to guide physicians worldwide in treating psoriasis in the clinical setting (eTable).^2-10

Because psoriasis is a complex disease with multiple comorbidities, applicability of these guidelines may be limited. Although some basic treatment algorithms exist, patient preference, disease severity, and other variables including comorbidities (eg, psoriatic arthritis [PsA], risk of major cardiac events, inflammatory bowel disease [IBD]), history of nonmelanoma skin cancer (NMSC), pregnancy and lactation, and specific contraindications to therapy (eg, renal failure, liver disease, active malignancy) should be considered. In this article, we summarize common themes across existing guidelines and consensus statements for the treatment of psoriasis and highlight areas where there is consistent agreement or lack of sufficient information.

Disease Severity and Treatment Outcomes

There currently are no consensus definitions for mild, moderate, and severe psoriasis, but several consensus statements have attempted to standardize grading systems based on objective values, such as body surface area (BSA) and psoriasis area and severity index (PASI)(a scoring system used to grade the degree of redness, thickness, and scaling of psoriasis plaques), as well as subjective QoL measures.^2,6 Although classification of disease severity varies, mild psoriasis generally is characterized as disease that can be managed with local and topical therapy, and moderate to severe psoriasis typically warrants consideration for escalated treatment with phototherapy or systemic agents.

Most definitions of disease severity in psoriasis reference 5% to 10% BSA involvement as a cutoff that should trigger consideration of systemic treatment; however, these criteria could result in undertreatment of patients with substantial disease. For example, patients who have limited BSA involvement but whose disease has a considerable impact on QoL, as well as those who have debilitating disease in localized areas (eg, palms, soles, scalp, nails) or substantial joint involvement may also be appropriate candidates for systemic treatment.^5,8

Once therapy is initiated, patients should be evaluated for appropriate treatment response at dedicated intervals. While the time to maximum therapeutic benefit depends on the agent of choice, European guidelines recommend that patients be evaluated after an induction phase (typically 16–24 weeks) and define treatment success as either (1) at least 75% improvement in PASI or (2) at least 50% improvement in PASI and a Dermatology Quality of Life Index (DLQI) score of 5 or lower.⁶

Alternatively, the National Psoriasis Foundation (NPF) recommended BSA as the preferred outcome measure in a recent consensus statement and concluded that an outcome of 3% or less BSA involvement or improvement in BSA of 75% or more is considered a desirable treatment response.⁹ Additionally, the Medicare Merit-based Incentive Payment System (MIPS) guidelines for successful systemic treatment response include at least 1 of the following: (1) physician global assessment score of 2 or lower, (2) BSA involvement of less than 3%, (3) PASI score lower than 3, or (4) DLQI score of 5 or lower.¹⁰

Although an array of outcome measures have been utilized in clinical trials and proposed in psoriasis guidelines and consensus statements, BSA is typically a manageable measure of treatment response in a clinical setting; however, DLQI should also be assessed if possible, particularly in patients with debilitating localized disease.⁹

Treatment Options

Because topical treatment regimens can be arduous and typically do not result in sustained clearance, patient expectations should be ascertained prior to initiation of therapy. Topical corticosteroids often can be used as monotherapy in patients with mild psoriasis.³ Topical vitamin D analogues and retinoids also can be effective; however, combined use of these agents with topical steroids should be considered to increase efficacy, and combination formulations can be prescribed to simplify application and improve adherence.

Treatment with UVB or psoralen plus UVA phototherapy is recommended for patients with moderate to severe psoriasis as well as in those who have had minimal response to topical therapy.⁴ Targeted phototherapy with an excimer laser can be used in patients with BSA involvement of less than 10%.

Methotrexate (MTX), cyclosporine, and acitretin are the most commonly prescribed systemic medications for severe psoriasis in the United States.⁵ Despite the risk for hepatotoxicity, MTX appears to have the best combined safety and efficacy profile in terms of serious adverse events compared to other systemic agents.¹¹ Guidelines for MTX monitoring, especially with regard to when to do a liver biopsy, have been substantially liberalized over time, and the recommended interval for biopsy has been extended by years; biopsy was previously recommended after a cumulative MTX dose of 1 to 1.5 g, but guidelines now suggest biopsy after 3.5 to 4 g in low-risk patients.⁵ While abnormally elevated liver function tests during treatment with MTX may necessitate liver biopsy, the use of transient elastography and a panel of serum biomarkers for liver function also can be used to monitor noninvasively for hepatotoxicity before biopsy is considered; these recommendations are likely to be incorporated into newer guidelines in development.¹² Methotrexate has demonstrated safety and increased efficacy when used in combination with biologic agents such as adalimumab, etanercept, infliximab, and secukinumab⁷ and has been studied in combination with many biologics indicated for PsA.¹³

Due to a considerable risk of glomerulosclerosis, cyclosporine is approved for a maximum of 1 year of continuous treatment of psoriasis in the United States and2 years in Europe.^5,7 Cyclosporine is best used as induction therapy in psoriasis patients with severe disease who are seeking faster abatement of symptoms.

Acitretin is another systemic treatment option, although efficacy of this agent is dose dependent. Higher dosing often is limited due to lower tolerability.⁵

Given that many insurance formularies primarily cover traditional systemic therapies and that MTX and phototherapy are generally well tolerated and cost effective, patients may need to be treated with traditional agents before escalating to biologics. Prior to starting treatment with any biologic, patients should typically be screened for tuberculosis (TB), human immunodeficiency virus infection, and immunization for, exposure to, and/or infection with hepatitis B and C virus, and any other active infections. In patients who do not demonstrate hepatitis immunity, the hepatitis B vaccine should be administered prior to starting treatment with a biologic.¹⁴ In psoriasis patients with latent TB, 2 months of treatment should be completed before initiating biologic therapy⁸; once a biologic has been initiated, all patients should be screened annually for TB.

European guidelines for biologic treatment recommend that complete blood count and liver and renal function be evaluated at baseline, at months 1 and 3 of treatment, and then every 3 to 6 months thereafter while on the biologic agent.⁷ These recommendations are more stringent than those indicated in regulatory labeling and, based on the continual accumulation of data regarding the safety of these agents, some investigators have argued that laboratory testing might not be necessary at all.¹⁵

Treatment in Special Populations

Psoriasis patients often present with comorbidities or a complicated medical history, which can make it challenging to decide which therapy is most suitable. Patients with comorbid diseases (eg, PsA, risk of major cardiac event, IBD) or a history of NMSC and those who are pregnant or are lactating require special considerations to ensure treatment safety and efficacy.

Tumor necrosis factor α (TNF-α) and IL-17 inhibitors are used in the treatment of joint disorders and should be considered in patients with PsA. IL-23/IL-12 inhibition appears to have less benefit in patients with PsA, but studies on IL-23 inhibition (p19 antibodies) alone are ongoing.¹⁶ It has been reported that TNF-α inhibition may be beneficial in patients at risk for major cardiac events.^8,17 In patients with IBD, IL-17 inhibitors should be avoided because they may exacerbate the condition; however, TNF-α and IL-23/IL-12 inhibition have shown to be safe in patients with IBD and many agents in these classes are approved by the US Food and Drug Administration for use in this population.^18,19

Although biologics may increase the risk of developing NMSC²⁰ and should generally be avoided in patients with any active malignancy, specific guidelines for screening and initiation of treatment in patients with a history of cancer are not clearly outlined. Prior to initiating systemic therapy in any patient, a careful medical history should be obtained. These agents often are not prescribed in patients with a history of cancer until remission has been established for at least 5 years, with the exception of patients with a history of treated NMSC.⁸ Annual skin monitoring for NMSC should be undertaken for psoriasis patients on most immunomodulating systemic therapies.

Recommendations for biologic treatment in psoriasis patients who are pregnant or lactating also are limited. European guidelines have noted pregnancy as an absolute contraindication to treatment with biologics,⁷but the regulatory guidance has recently changed for some agents, so this recommendation also may evolve.²¹ British⁸ and US⁵ guidelines do not consider pregnancy a contraindication for treatment with biologics.

Information on the safety of TNF-α antagonists during pregnancy comes primarily from use in patients with IBD and rheumatologic disease. To date, reports on the incidence of congenital malformations have been generally reassuring. Because IgG antibodies are actively transferred across the placenta in the late-second or the third trimesters, neonates born to mothers on biologic treatments may have high levels of some biologic drugs at birth. As a result, live vaccination should be avoided in neonates whose mothers were treated with IgG-based biologics.

Changing Treatment Agents

Patients may need to stop and change treatment agents due to ineffectiveness, personal preference, or worsening disease. When transitioning from any systemic or biologic agent to another (other than MTX), the British Association of Dermatologists recommends a washout period of at least 1 month before initiating a new therapy.⁸ Most guidelines do not define parameters for therapy escalation when patients fail multiple systemic agents, so physicians should use clinical judgment along with consideration of patient preference and comorbidity profile to ascertain which agent is most appropriate.

Conclusion

Keeping psoriasis treatment guidelines updated can be difficult, especially as new therapeutic options for psoriasis and treatment regimens rapidly evolve. Regulatory recommendations also vary worldwide, but most guidelines are reasonably consistent without being overly prescriptive, appropriately allowing for flexibility for application in clinical practice. Nonetheless, physicians should keep in mind new or changing guidelines while tailoring psoriasis treatment recommendations to best suit their individual patients.

Psoriasis is a chronic autoinflammatory disorder affecting approximately 2% to 4% of the Western population.¹ While there is no absolute cure for psoriasis, novel therapies allow for substantial reduction in symptoms and considerable improvement in quality of life (QoL). In the past few years, multiple treatment guidelines (recommendations based on evidence-based literature reviews) and consensus statements (a set of declarations determined and voted on by a panel of experts in the field) have been developed to guide physicians worldwide in treating psoriasis in the clinical setting (eTable).^2-10

Because psoriasis is a complex disease with multiple comorbidities, applicability of these guidelines may be limited. Although some basic treatment algorithms exist, patient preference, disease severity, and other variables including comorbidities (eg, psoriatic arthritis [PsA], risk of major cardiac events, inflammatory bowel disease [IBD]), history of nonmelanoma skin cancer (NMSC), pregnancy and lactation, and specific contraindications to therapy (eg, renal failure, liver disease, active malignancy) should be considered. In this article, we summarize common themes across existing guidelines and consensus statements for the treatment of psoriasis and highlight areas where there is consistent agreement or lack of sufficient information.

Disease Severity and Treatment Outcomes

There currently are no consensus definitions for mild, moderate, and severe psoriasis, but several consensus statements have attempted to standardize grading systems based on objective values, such as body surface area (BSA) and psoriasis area and severity index (PASI)(a scoring system used to grade the degree of redness, thickness, and scaling of psoriasis plaques), as well as subjective QoL measures.^2,6 Although classification of disease severity varies, mild psoriasis generally is characterized as disease that can be managed with local and topical therapy, and moderate to severe psoriasis typically warrants consideration for escalated treatment with phototherapy or systemic agents.

Most definitions of disease severity in psoriasis reference 5% to 10% BSA involvement as a cutoff that should trigger consideration of systemic treatment; however, these criteria could result in undertreatment of patients with substantial disease. For example, patients who have limited BSA involvement but whose disease has a considerable impact on QoL, as well as those who have debilitating disease in localized areas (eg, palms, soles, scalp, nails) or substantial joint involvement may also be appropriate candidates for systemic treatment.^5,8

Once therapy is initiated, patients should be evaluated for appropriate treatment response at dedicated intervals. While the time to maximum therapeutic benefit depends on the agent of choice, European guidelines recommend that patients be evaluated after an induction phase (typically 16–24 weeks) and define treatment success as either (1) at least 75% improvement in PASI or (2) at least 50% improvement in PASI and a Dermatology Quality of Life Index (DLQI) score of 5 or lower.⁶

Alternatively, the National Psoriasis Foundation (NPF) recommended BSA as the preferred outcome measure in a recent consensus statement and concluded that an outcome of 3% or less BSA involvement or improvement in BSA of 75% or more is considered a desirable treatment response.⁹ Additionally, the Medicare Merit-based Incentive Payment System (MIPS) guidelines for successful systemic treatment response include at least 1 of the following: (1) physician global assessment score of 2 or lower, (2) BSA involvement of less than 3%, (3) PASI score lower than 3, or (4) DLQI score of 5 or lower.¹⁰

Although an array of outcome measures have been utilized in clinical trials and proposed in psoriasis guidelines and consensus statements, BSA is typically a manageable measure of treatment response in a clinical setting; however, DLQI should also be assessed if possible, particularly in patients with debilitating localized disease.⁹

Treatment Options

Because topical treatment regimens can be arduous and typically do not result in sustained clearance, patient expectations should be ascertained prior to initiation of therapy. Topical corticosteroids often can be used as monotherapy in patients with mild psoriasis.³ Topical vitamin D analogues and retinoids also can be effective; however, combined use of these agents with topical steroids should be considered to increase efficacy, and combination formulations can be prescribed to simplify application and improve adherence.

Treatment with UVB or psoralen plus UVA phototherapy is recommended for patients with moderate to severe psoriasis as well as in those who have had minimal response to topical therapy.⁴ Targeted phototherapy with an excimer laser can be used in patients with BSA involvement of less than 10%.

Methotrexate (MTX), cyclosporine, and acitretin are the most commonly prescribed systemic medications for severe psoriasis in the United States.⁵ Despite the risk for hepatotoxicity, MTX appears to have the best combined safety and efficacy profile in terms of serious adverse events compared to other systemic agents.¹¹ Guidelines for MTX monitoring, especially with regard to when to do a liver biopsy, have been substantially liberalized over time, and the recommended interval for biopsy has been extended by years; biopsy was previously recommended after a cumulative MTX dose of 1 to 1.5 g, but guidelines now suggest biopsy after 3.5 to 4 g in low-risk patients.⁵ While abnormally elevated liver function tests during treatment with MTX may necessitate liver biopsy, the use of transient elastography and a panel of serum biomarkers for liver function also can be used to monitor noninvasively for hepatotoxicity before biopsy is considered; these recommendations are likely to be incorporated into newer guidelines in development.¹² Methotrexate has demonstrated safety and increased efficacy when used in combination with biologic agents such as adalimumab, etanercept, infliximab, and secukinumab⁷ and has been studied in combination with many biologics indicated for PsA.¹³

Due to a considerable risk of glomerulosclerosis, cyclosporine is approved for a maximum of 1 year of continuous treatment of psoriasis in the United States and2 years in Europe.^5,7 Cyclosporine is best used as induction therapy in psoriasis patients with severe disease who are seeking faster abatement of symptoms.

Acitretin is another systemic treatment option, although efficacy of this agent is dose dependent. Higher dosing often is limited due to lower tolerability.⁵

Given that many insurance formularies primarily cover traditional systemic therapies and that MTX and phototherapy are generally well tolerated and cost effective, patients may need to be treated with traditional agents before escalating to biologics. Prior to starting treatment with any biologic, patients should typically be screened for tuberculosis (TB), human immunodeficiency virus infection, and immunization for, exposure to, and/or infection with hepatitis B and C virus, and any other active infections. In patients who do not demonstrate hepatitis immunity, the hepatitis B vaccine should be administered prior to starting treatment with a biologic.¹⁴ In psoriasis patients with latent TB, 2 months of treatment should be completed before initiating biologic therapy⁸; once a biologic has been initiated, all patients should be screened annually for TB.

European guidelines for biologic treatment recommend that complete blood count and liver and renal function be evaluated at baseline, at months 1 and 3 of treatment, and then every 3 to 6 months thereafter while on the biologic agent.⁷ These recommendations are more stringent than those indicated in regulatory labeling and, based on the continual accumulation of data regarding the safety of these agents, some investigators have argued that laboratory testing might not be necessary at all.¹⁵

Treatment in Special Populations

Psoriasis patients often present with comorbidities or a complicated medical history, which can make it challenging to decide which therapy is most suitable. Patients with comorbid diseases (eg, PsA, risk of major cardiac event, IBD) or a history of NMSC and those who are pregnant or are lactating require special considerations to ensure treatment safety and efficacy.

Tumor necrosis factor α (TNF-α) and IL-17 inhibitors are used in the treatment of joint disorders and should be considered in patients with PsA. IL-23/IL-12 inhibition appears to have less benefit in patients with PsA, but studies on IL-23 inhibition (p19 antibodies) alone are ongoing.¹⁶ It has been reported that TNF-α inhibition may be beneficial in patients at risk for major cardiac events.^8,17 In patients with IBD, IL-17 inhibitors should be avoided because they may exacerbate the condition; however, TNF-α and IL-23/IL-12 inhibition have shown to be safe in patients with IBD and many agents in these classes are approved by the US Food and Drug Administration for use in this population.^18,19

Although biologics may increase the risk of developing NMSC²⁰ and should generally be avoided in patients with any active malignancy, specific guidelines for screening and initiation of treatment in patients with a history of cancer are not clearly outlined. Prior to initiating systemic therapy in any patient, a careful medical history should be obtained. These agents often are not prescribed in patients with a history of cancer until remission has been established for at least 5 years, with the exception of patients with a history of treated NMSC.⁸ Annual skin monitoring for NMSC should be undertaken for psoriasis patients on most immunomodulating systemic therapies.

Recommendations for biologic treatment in psoriasis patients who are pregnant or lactating also are limited. European guidelines have noted pregnancy as an absolute contraindication to treatment with biologics,⁷but the regulatory guidance has recently changed for some agents, so this recommendation also may evolve.²¹ British⁸ and US⁵ guidelines do not consider pregnancy a contraindication for treatment with biologics.

Information on the safety of TNF-α antagonists during pregnancy comes primarily from use in patients with IBD and rheumatologic disease. To date, reports on the incidence of congenital malformations have been generally reassuring. Because IgG antibodies are actively transferred across the placenta in the late-second or the third trimesters, neonates born to mothers on biologic treatments may have high levels of some biologic drugs at birth. As a result, live vaccination should be avoided in neonates whose mothers were treated with IgG-based biologics.

Changing Treatment Agents

Patients may need to stop and change treatment agents due to ineffectiveness, personal preference, or worsening disease. When transitioning from any systemic or biologic agent to another (other than MTX), the British Association of Dermatologists recommends a washout period of at least 1 month before initiating a new therapy.⁸ Most guidelines do not define parameters for therapy escalation when patients fail multiple systemic agents, so physicians should use clinical judgment along with consideration of patient preference and comorbidity profile to ascertain which agent is most appropriate.

Conclusion

Keeping psoriasis treatment guidelines updated can be difficult, especially as new therapeutic options for psoriasis and treatment regimens rapidly evolve. Regulatory recommendations also vary worldwide, but most guidelines are reasonably consistent without being overly prescriptive, appropriately allowing for flexibility for application in clinical practice. Nonetheless, physicians should keep in mind new or changing guidelines while tailoring psoriasis treatment recommendations to best suit their individual patients.

Interest in hidradenitis suppurativa (HS) has exploded in the last few years. A PubMed search of articles indexed for MEDLINE using the MeSH term hidradenitis suppurativa yielded more than 900 articles on HS since 1947, with a sharp increase in publications over the last few years and 119 articles published in 2015 alone. In addition to publications, we recently saw adalimumab become the first and only US Food and Drug Administration–approved treatment of moderate to severe HS.

With new treatment options and enthusiasm for HS, further attention needs to be paid to the scoring systems or outcome measures that clinicians use to grade HS severity and disease. Utilization of validated outcome measures allows for comparability between treatment effects, which is essential for clinical trials, meta-analyses, and monitoring of treatment response in daily clinical practice. Designing a scoring scale for any dermatologic disease is challenging; however, as we move forward with value-based reimbursement models, we likely will encounter quality reporting guidelines that mandate providers demonstrate the positive impact of treatment. Thus, scoring systems for HS, particularly ones that accurately assess this impact of treatment, are essential. For psoriasis, the physician global assessment (PGA) and psoriasis area and severity index are standard outcome measures of disease severity in clinical trials. The PGA also can be used in a clinical setting to longitudinally track patient treatment outcomes.¹ Both the psoriasis area and severity index and PGA were cited as acceptable scoring tools for Medicare’s Physician Quality Reporting System quality metrics reporting (Measure #410: Psoriasis: Clinical Response to Oral Systemic or Biologic Medications). Unfortunately, no such outcome measures consensus currently exists for scoring systems in HS.

Many scoring systems have been proposed for HS. The most well known is the Hurley staging system. Developed in 1989 for surgical approaches, it is a straightforward tool to categorize disease severity but does not emphasize the inflammatory component of HS. Recently, a refined Hurley stage classification system was proposed. This 3-step algorithm expanded the Hurley stage classification to incorporate disease extensiveness, degree of inflammation, and presence of sinus tracts.² The modified Sartorius score (also known as the modified HS score) is a more detailed scoring system for assessing disease activity that requires measurements and precise counting of lesions.³ The HS-PGA is an ordinal scale specific to HS that categorizes patients into clear, minimal, mild, moderate, severe, or very severe disease, and it was used successfully in a phase 2 interventional clinical trial.⁴ The HS clinical response (HiSCR) score is an HS-specific, binary scoring system for patients with 3 or more abscesses or inflammatory nodules. It was engineered using raw data and outcomes from a large clinical trial, and subsequently was employed as the primary end point in 2 randomized controlled trials.^5,6 It is the only HS scoring system to undergo an extensive validation process of both physician- and patient-reported measures for assessment of therapeutic response in controlling the inflammatory manifestations of HS.

Designing a scoring system for clinical trials can be complicated. Sample sizes are dependent on the delta, or change, in efficacy or variation in response, and the design of the score will affect how easy it is to detect a statistically meaningful difference. These choices are a critical part of the design of small studies, particularly if obtaining enough statistical power can be challenging. Additionally, it is easier to detect change in more homogenous populations where we expect a more consistent response. Hidradenitis suppurativa is not a particularly homogenous disease, which furthers the risk of designing a trial that cannot detect important differences. The PGA often is required by the US Food and Drug Administration and has the major advantage that it is easy to understand, but the categories can sometimes be too broad to detect change easily, and more granular data can provide the basis for more in-depth analyses. An ideal outcome measure is a simplified scoring system that assesses disease severity and responsiveness to treatment while accurately serving as a surrogate for patient-reported outcomes, such as the dermatology life quality index, visual analog scale for HS skin pain, the work productivity and activity impairment questionnaire (specific health problem), or the patient global assessment. Validation processes for outcome measures, such as the one that HiSCR underwent, are essential to ensure that the proposed scoring system has clinical meaningfulness to both the physician and patient.

A 2016 Cochrane review of interventions for HS included 12 randomized controlled trials that employed a total of 30 different outcome measures instruments. Because use of multiple scoring systems makes it difficult to compare analyses of treatment, the authors concluded that there was a need for improved validation of HS outcome measures for future clinical trials.⁷ Schmitt et al⁸ recognized that atopic dermatitis also was in a similar predicament; they noted that more than 20 outcome measures were employed to assess disease severity in clinical trials. The authors called this situation “a significant threat to evidence-based health care” and outlined the Harmonizing Outcome Measures for Eczema (HOME) research initiative’s methodology for creation of core outcome sets for any dermatologic disease. Their consensus process involved first identifying what to measure, termed outcome domains, followed by developing how to measure these domains through outcome measures instruments, which would be assessed for validity, reliability, sensitivity to change, and feasibility.⁸

Using the framework set forth by the HOME initiative and data from the 2016 Cochrane review,⁷ a recent review of all outcome measures instruments currently employed in HS found that 90% (27/30) were not validated.⁹ Even those that were validated still could not be fully recommended by the authors. The authors identified 10 potential outcome domains for measurement, including quality of life, pain, lesion count, PGA, patient global self-assessment, recurrence rate, overall satisfaction with treatment, impairment of function, cosmesis, and duration of recovery. They recommended a further consensus process to better define these outcomes.⁹

Measuring all of these variables seems daunting, but as the speed of HS research rapidly progresses, we would greatly benefit from employing a standard validated scoring system that captures both disease severity and activity. Several groups are working to improve our current tools, but we will need to move quickly to a common approach so we can better compare treatment effects and build an evidence base for treatment decisions. For now, the HiSCR is the most validated clinical trials instrument, but it may not be ideal for the clinical setting. In our practice, we grade all patients each visit with Hurley staging, the validated HS-PGA scoring system to track improvement in inflammatory lesions, and a 10-point pain scale to monitor disease activity and severity. We have found these tools to be quick and effective for measuring treatment response and would recommend employment of these scoring systems as a standard measure in clinical practice until further consensus is reached.

Interest in hidradenitis suppurativa (HS) has exploded in the last few years. A PubMed search of articles indexed for MEDLINE using the MeSH term hidradenitis suppurativa yielded more than 900 articles on HS since 1947, with a sharp increase in publications over the last few years and 119 articles published in 2015 alone. In addition to publications, we recently saw adalimumab become the first and only US Food and Drug Administration–approved treatment of moderate to severe HS.

With new treatment options and enthusiasm for HS, further attention needs to be paid to the scoring systems or outcome measures that clinicians use to grade HS severity and disease. Utilization of validated outcome measures allows for comparability between treatment effects, which is essential for clinical trials, meta-analyses, and monitoring of treatment response in daily clinical practice. Designing a scoring scale for any dermatologic disease is challenging; however, as we move forward with value-based reimbursement models, we likely will encounter quality reporting guidelines that mandate providers demonstrate the positive impact of treatment. Thus, scoring systems for HS, particularly ones that accurately assess this impact of treatment, are essential. For psoriasis, the physician global assessment (PGA) and psoriasis area and severity index are standard outcome measures of disease severity in clinical trials. The PGA also can be used in a clinical setting to longitudinally track patient treatment outcomes.¹ Both the psoriasis area and severity index and PGA were cited as acceptable scoring tools for Medicare’s Physician Quality Reporting System quality metrics reporting (Measure #410: Psoriasis: Clinical Response to Oral Systemic or Biologic Medications). Unfortunately, no such outcome measures consensus currently exists for scoring systems in HS.

Many scoring systems have been proposed for HS. The most well known is the Hurley staging system. Developed in 1989 for surgical approaches, it is a straightforward tool to categorize disease severity but does not emphasize the inflammatory component of HS. Recently, a refined Hurley stage classification system was proposed. This 3-step algorithm expanded the Hurley stage classification to incorporate disease extensiveness, degree of inflammation, and presence of sinus tracts.² The modified Sartorius score (also known as the modified HS score) is a more detailed scoring system for assessing disease activity that requires measurements and precise counting of lesions.³ The HS-PGA is an ordinal scale specific to HS that categorizes patients into clear, minimal, mild, moderate, severe, or very severe disease, and it was used successfully in a phase 2 interventional clinical trial.⁴ The HS clinical response (HiSCR) score is an HS-specific, binary scoring system for patients with 3 or more abscesses or inflammatory nodules. It was engineered using raw data and outcomes from a large clinical trial, and subsequently was employed as the primary end point in 2 randomized controlled trials.^5,6 It is the only HS scoring system to undergo an extensive validation process of both physician- and patient-reported measures for assessment of therapeutic response in controlling the inflammatory manifestations of HS.

Designing a scoring system for clinical trials can be complicated. Sample sizes are dependent on the delta, or change, in efficacy or variation in response, and the design of the score will affect how easy it is to detect a statistically meaningful difference. These choices are a critical part of the design of small studies, particularly if obtaining enough statistical power can be challenging. Additionally, it is easier to detect change in more homogenous populations where we expect a more consistent response. Hidradenitis suppurativa is not a particularly homogenous disease, which furthers the risk of designing a trial that cannot detect important differences. The PGA often is required by the US Food and Drug Administration and has the major advantage that it is easy to understand, but the categories can sometimes be too broad to detect change easily, and more granular data can provide the basis for more in-depth analyses. An ideal outcome measure is a simplified scoring system that assesses disease severity and responsiveness to treatment while accurately serving as a surrogate for patient-reported outcomes, such as the dermatology life quality index, visual analog scale for HS skin pain, the work productivity and activity impairment questionnaire (specific health problem), or the patient global assessment. Validation processes for outcome measures, such as the one that HiSCR underwent, are essential to ensure that the proposed scoring system has clinical meaningfulness to both the physician and patient.

A 2016 Cochrane review of interventions for HS included 12 randomized controlled trials that employed a total of 30 different outcome measures instruments. Because use of multiple scoring systems makes it difficult to compare analyses of treatment, the authors concluded that there was a need for improved validation of HS outcome measures for future clinical trials.⁷ Schmitt et al⁸ recognized that atopic dermatitis also was in a similar predicament; they noted that more than 20 outcome measures were employed to assess disease severity in clinical trials. The authors called this situation “a significant threat to evidence-based health care” and outlined the Harmonizing Outcome Measures for Eczema (HOME) research initiative’s methodology for creation of core outcome sets for any dermatologic disease. Their consensus process involved first identifying what to measure, termed outcome domains, followed by developing how to measure these domains through outcome measures instruments, which would be assessed for validity, reliability, sensitivity to change, and feasibility.⁸

Using the framework set forth by the HOME initiative and data from the 2016 Cochrane review,⁷ a recent review of all outcome measures instruments currently employed in HS found that 90% (27/30) were not validated.⁹ Even those that were validated still could not be fully recommended by the authors. The authors identified 10 potential outcome domains for measurement, including quality of life, pain, lesion count, PGA, patient global self-assessment, recurrence rate, overall satisfaction with treatment, impairment of function, cosmesis, and duration of recovery. They recommended a further consensus process to better define these outcomes.⁹

Measuring all of these variables seems daunting, but as the speed of HS research rapidly progresses, we would greatly benefit from employing a standard validated scoring system that captures both disease severity and activity. Several groups are working to improve our current tools, but we will need to move quickly to a common approach so we can better compare treatment effects and build an evidence base for treatment decisions. For now, the HiSCR is the most validated clinical trials instrument, but it may not be ideal for the clinical setting. In our practice, we grade all patients each visit with Hurley staging, the validated HS-PGA scoring system to track improvement in inflammatory lesions, and a 10-point pain scale to monitor disease activity and severity. We have found these tools to be quick and effective for measuring treatment response and would recommend employment of these scoring systems as a standard measure in clinical practice until further consensus is reached.

Interest in hidradenitis suppurativa (HS) has exploded in the last few years. A PubMed search of articles indexed for MEDLINE using the MeSH term hidradenitis suppurativa yielded more than 900 articles on HS since 1947, with a sharp increase in publications over the last few years and 119 articles published in 2015 alone. In addition to publications, we recently saw adalimumab become the first and only US Food and Drug Administration–approved treatment of moderate to severe HS.

With new treatment options and enthusiasm for HS, further attention needs to be paid to the scoring systems or outcome measures that clinicians use to grade HS severity and disease. Utilization of validated outcome measures allows for comparability between treatment effects, which is essential for clinical trials, meta-analyses, and monitoring of treatment response in daily clinical practice. Designing a scoring scale for any dermatologic disease is challenging; however, as we move forward with value-based reimbursement models, we likely will encounter quality reporting guidelines that mandate providers demonstrate the positive impact of treatment. Thus, scoring systems for HS, particularly ones that accurately assess this impact of treatment, are essential. For psoriasis, the physician global assessment (PGA) and psoriasis area and severity index are standard outcome measures of disease severity in clinical trials. The PGA also can be used in a clinical setting to longitudinally track patient treatment outcomes.¹ Both the psoriasis area and severity index and PGA were cited as acceptable scoring tools for Medicare’s Physician Quality Reporting System quality metrics reporting (Measure #410: Psoriasis: Clinical Response to Oral Systemic or Biologic Medications). Unfortunately, no such outcome measures consensus currently exists for scoring systems in HS.

Many scoring systems have been proposed for HS. The most well known is the Hurley staging system. Developed in 1989 for surgical approaches, it is a straightforward tool to categorize disease severity but does not emphasize the inflammatory component of HS. Recently, a refined Hurley stage classification system was proposed. This 3-step algorithm expanded the Hurley stage classification to incorporate disease extensiveness, degree of inflammation, and presence of sinus tracts.² The modified Sartorius score (also known as the modified HS score) is a more detailed scoring system for assessing disease activity that requires measurements and precise counting of lesions.³ The HS-PGA is an ordinal scale specific to HS that categorizes patients into clear, minimal, mild, moderate, severe, or very severe disease, and it was used successfully in a phase 2 interventional clinical trial.⁴ The HS clinical response (HiSCR) score is an HS-specific, binary scoring system for patients with 3 or more abscesses or inflammatory nodules. It was engineered using raw data and outcomes from a large clinical trial, and subsequently was employed as the primary end point in 2 randomized controlled trials.^5,6 It is the only HS scoring system to undergo an extensive validation process of both physician- and patient-reported measures for assessment of therapeutic response in controlling the inflammatory manifestations of HS.

Designing a scoring system for clinical trials can be complicated. Sample sizes are dependent on the delta, or change, in efficacy or variation in response, and the design of the score will affect how easy it is to detect a statistically meaningful difference. These choices are a critical part of the design of small studies, particularly if obtaining enough statistical power can be challenging. Additionally, it is easier to detect change in more homogenous populations where we expect a more consistent response. Hidradenitis suppurativa is not a particularly homogenous disease, which furthers the risk of designing a trial that cannot detect important differences. The PGA often is required by the US Food and Drug Administration and has the major advantage that it is easy to understand, but the categories can sometimes be too broad to detect change easily, and more granular data can provide the basis for more in-depth analyses. An ideal outcome measure is a simplified scoring system that assesses disease severity and responsiveness to treatment while accurately serving as a surrogate for patient-reported outcomes, such as the dermatology life quality index, visual analog scale for HS skin pain, the work productivity and activity impairment questionnaire (specific health problem), or the patient global assessment. Validation processes for outcome measures, such as the one that HiSCR underwent, are essential to ensure that the proposed scoring system has clinical meaningfulness to both the physician and patient.

A 2016 Cochrane review of interventions for HS included 12 randomized controlled trials that employed a total of 30 different outcome measures instruments. Because use of multiple scoring systems makes it difficult to compare analyses of treatment, the authors concluded that there was a need for improved validation of HS outcome measures for future clinical trials.⁷ Schmitt et al⁸ recognized that atopic dermatitis also was in a similar predicament; they noted that more than 20 outcome measures were employed to assess disease severity in clinical trials. The authors called this situation “a significant threat to evidence-based health care” and outlined the Harmonizing Outcome Measures for Eczema (HOME) research initiative’s methodology for creation of core outcome sets for any dermatologic disease. Their consensus process involved first identifying what to measure, termed outcome domains, followed by developing how to measure these domains through outcome measures instruments, which would be assessed for validity, reliability, sensitivity to change, and feasibility.⁸

Using the framework set forth by the HOME initiative and data from the 2016 Cochrane review,⁷ a recent review of all outcome measures instruments currently employed in HS found that 90% (27/30) were not validated.⁹ Even those that were validated still could not be fully recommended by the authors. The authors identified 10 potential outcome domains for measurement, including quality of life, pain, lesion count, PGA, patient global self-assessment, recurrence rate, overall satisfaction with treatment, impairment of function, cosmesis, and duration of recovery. They recommended a further consensus process to better define these outcomes.⁹

Measuring all of these variables seems daunting, but as the speed of HS research rapidly progresses, we would greatly benefit from employing a standard validated scoring system that captures both disease severity and activity. Several groups are working to improve our current tools, but we will need to move quickly to a common approach so we can better compare treatment effects and build an evidence base for treatment decisions. For now, the HiSCR is the most validated clinical trials instrument, but it may not be ideal for the clinical setting. In our practice, we grade all patients each visit with Hurley staging, the validated HS-PGA scoring system to track improvement in inflammatory lesions, and a 10-point pain scale to monitor disease activity and severity. We have found these tools to be quick and effective for measuring treatment response and would recommend employment of these scoring systems as a standard measure in clinical practice until further consensus is reached.