Dermatology

THE CASE

A 37-year-old man presented with a sudden-onset, nonpruritic, nonpainful, papular rash of 1 month’s duration on his trunk and both arms and legs. Two weeks prior to the current presentation, he consulted a general practitioner, who treated the rash with a course of unknown oral antibiotics; the patient showed no improvement. He recalled that on a few occasions, he used his fingers to express a creamy discharge from some of the lesions. This temporarily reduced the size of those papules.

His medical history was unremarkable except for morbid obesity. He did not drink alcohol regularly and was not taking any medications prior to the onset of the rash. He had no family history of hyperlipidemia, but his mother had a history of diabetes mellitus.

Physical examination showed numerous discrete erythematous papules with a creamy center on his trunk and his arms and legs. The lesions were more numerous on the extensor surfaces of the arms and legs. Some of the papules coalesced to form small plaques (FIGURE). There was no scaling, and the lesions were firm in texture. The patient’s face was spared, and there was no mucosal involvement. The patient was otherwise systemically well.

THE DIAGNOSIS

Based on the morphology, distribution, and abrupt onset of the diffuse nonpruritic papules in this morbidly obese (but otherwise systemically well) middle-aged man, a clinical diagnosis of eruptive xanthoma was suspected. Subsequent blood testing revealed an elevated serum triglyceride level of 47.8 mmol/L (reference range, <1.7 mmol/L), elevated serum total cholesterol of 7.1 mmol/L (reference range, <6.2 mmol/L), and low serum high-density lipoprotein cholesterol of 0.7 mmol/L (reference range, >1 mmol/L in men). He also had an elevated fasting serum glucose level of 12.9 mmol/L (reference range, 3.9–5.6 mmol/L) and an elevated hemoglobin A1c (glycated hemoglobin) level of 10.9%.

Subsequent thyroid, liver, and renal function tests were normal, but the patient had heavy proteinuria, with an elevated urine albumin-to-creatinine ratio of 355.6 mg/mmol (reference range, ≤2.5 mg/mmol). The patient was referred to a dermatologist, who confirmed the clinical diagnosis without the need for a skin biopsy.

DISCUSSION

Xanthomas are lipid deposits in the skin and subcutaneous tissues that arise in the setting of hyperlipidemia and are caused by underlying familial or acquired disorders. Xanthomas associated with dyslipidemias include eruptive xanthoma, tendinous xanthoma, xanthoma palpebrarum, and xanthoma tuberosum (TABLE).^1-3 Other non–dyslipidemia-related xanthomas include xanthoma planum, xanthoma disseminatum, linear palmar xanthomas, and verrucous xanthoma. One retrospective cohort study reported an 8.5% (8/95) prevalence of eruptive xanthomas in patients with severe hypertriglyceridemia (ie, triglyceride levels >1770 mg/dL).⁴ Data on the prevalence of other variants of xanthoma are lacking.

Diagnosis of eruptive xanthoma can be confirmed by skin biopsy if other conditions in the differential diagnosis can’t be ruled out or if the lesions do not resolve with treatment.

Eruptive xanthoma is characterized by an abrupt onset of crops of multiple yellowish to brownish papules that can coalesce into small plaques. The lesions can be generalized, but tend to be more densely distributed on the extensor surfaces of the arms and legs, buttocks, and thighs.⁵ Eruptive xanthoma often is associated with hypertriglyceridemia, which can be primary—as a result of a genetic defect caused by familial hypertriglyceridemia—or secondary, associated with poorly controlled diabetes mellitus, morbid obesity, excessive alcohol consumption, nephrotic syndrome, hypothyroidism, primary biliary cholangitis, and drugs like estrogen replacement therapies, corticosteroids, and isotretinoin.⁶ Pruritus and tenderness may or may not be present, and the Köbner phenomenon may occur.⁷

Continue to: The differential diagnosis

The differential diagnosis for eruptive xanthoma includes xanthoma disseminatum, non–Langerhans cell histiocytoses (eg, generalized eruptive histiocytosis), and cutaneous mastocytosis.¹

Xanthoma disseminatum is an extremely rare, but benign, disorder of non–Langerhans cell origin. The average age of onset is older than 40 years. The rash consists of multiple red-yellow papules and nodules that most commonly present in flexural areas. Forty percent to 60% of patients have mucosal involvement, and rarely the central nervous system is involved.⁸

Generalized eruptive histiocytosis is another rare non–Langerhans cell histiocytosis that occurs mainly in adults and is characterized by widespread, symmetric, red-brown papules on the trunk, arms, and legs, and rarely the mucous membranes.⁹

Cutaneous mastocytosis, especially xanthelasmoid mastocytosis, consists of multiple pruritic, yellowish, papular or nodular lesions that may mimic eruptive xanthoma. It occurs mainly in children and rarely in adults.¹⁰

Confirming the diagnosis, initiating treatment

The diagnosis of eruptive xanthoma can be confirmed by skin biopsy if other differential diagnoses cannot be ruled out or the lesions do not resolve with treatment. Skin biopsy will reveal lipid-laden macrophages (known as foam cells) deposited in the dermis.⁷

Continue to: Treatment of eruptive xanthoma

Treatment of eruptive xanthoma involves management of the underlying causes of the condition. In most cases, dietary control, intensive triglyceride-lowering therapies, and treatment of other secondary causes of hypertriglyceridemia result in complete resolution of the lesions within several weeks.⁵

Our patient’s outcome

Our patient’s sudden-onset rash alerted us to the presence of type 2 diabetes mellitus, hypertriglyceridemia, and heavy proteinuria, which he was not aware of previously. We counselled him about stringent low-sugar, low-lipid diet control and exercise, and we started him on metformin and gemfibrozil. He was referred to an internal medicine specialist for further assessment and management of his severe hypertriglyceridemia and heavy proteinuria.

Eruptive xanthoma may be an indicator of severe hypertriglyceri- demia, which can be associated with an increased risk for acute pancreatitis.

The rash started to wane 1 month after the patient started the metformin and gemfibrozil, and his drug regimen was changed to combination therapy with metformin/glimepiride and fenofibrate/simvastatin 6 weeks later when he was seen in the medical specialty clinic. Fundus photography performed 1 month after starting oral antidiabetic therapy showed no diabetic retinopathy or lipemia retinalis.

After 3 months of treatment, his serum triglycerides and hemoglobin A1c levels dropped to 3.8 mmol/L and 8.7%, respectively. The rash also resolved considerably, with only residual papules on the abdomen. This rapid clinical response to treatment of the underlying hypertriglyceridemia and diabetes further supported the clinical diagnosis of eruptive xanthoma.

THE TAKEAWAY

Eruptive xanthoma is relatively rare, but it is important for family physicians to recognize this clinical presentation as a potential indicator of severe hypertriglyceridemia. Recognizing hypertriglyceridemia early is important, as it can be associated with an increased risk for acute pancreatitis. Moreover, eruptive xanthoma might be the sole presenting symptom of underlying diabetes mellitus or familial hyperlipidemia, both of which can lead to a significant increase in cardiovascular risk if uncontrolled.

CORRESPONDENCE
Chan Kam Sum, MBChB, FRACGP, Tseung Kwan O Jockey Club General Out-patient Clinic, 99 Po Lam Road North, G/F, Tseung Kwan O, Kowloon, Hong Kong; [email protected]

THE CASE

A 37-year-old man presented with a sudden-onset, nonpruritic, nonpainful, papular rash of 1 month’s duration on his trunk and both arms and legs. Two weeks prior to the current presentation, he consulted a general practitioner, who treated the rash with a course of unknown oral antibiotics; the patient showed no improvement. He recalled that on a few occasions, he used his fingers to express a creamy discharge from some of the lesions. This temporarily reduced the size of those papules.

His medical history was unremarkable except for morbid obesity. He did not drink alcohol regularly and was not taking any medications prior to the onset of the rash. He had no family history of hyperlipidemia, but his mother had a history of diabetes mellitus.

Physical examination showed numerous discrete erythematous papules with a creamy center on his trunk and his arms and legs. The lesions were more numerous on the extensor surfaces of the arms and legs. Some of the papules coalesced to form small plaques (FIGURE). There was no scaling, and the lesions were firm in texture. The patient’s face was spared, and there was no mucosal involvement. The patient was otherwise systemically well.

THE DIAGNOSIS

Based on the morphology, distribution, and abrupt onset of the diffuse nonpruritic papules in this morbidly obese (but otherwise systemically well) middle-aged man, a clinical diagnosis of eruptive xanthoma was suspected. Subsequent blood testing revealed an elevated serum triglyceride level of 47.8 mmol/L (reference range, <1.7 mmol/L), elevated serum total cholesterol of 7.1 mmol/L (reference range, <6.2 mmol/L), and low serum high-density lipoprotein cholesterol of 0.7 mmol/L (reference range, >1 mmol/L in men). He also had an elevated fasting serum glucose level of 12.9 mmol/L (reference range, 3.9–5.6 mmol/L) and an elevated hemoglobin A1c (glycated hemoglobin) level of 10.9%.

Subsequent thyroid, liver, and renal function tests were normal, but the patient had heavy proteinuria, with an elevated urine albumin-to-creatinine ratio of 355.6 mg/mmol (reference range, ≤2.5 mg/mmol). The patient was referred to a dermatologist, who confirmed the clinical diagnosis without the need for a skin biopsy.

DISCUSSION

Xanthomas are lipid deposits in the skin and subcutaneous tissues that arise in the setting of hyperlipidemia and are caused by underlying familial or acquired disorders. Xanthomas associated with dyslipidemias include eruptive xanthoma, tendinous xanthoma, xanthoma palpebrarum, and xanthoma tuberosum (TABLE).^1-3 Other non–dyslipidemia-related xanthomas include xanthoma planum, xanthoma disseminatum, linear palmar xanthomas, and verrucous xanthoma. One retrospective cohort study reported an 8.5% (8/95) prevalence of eruptive xanthomas in patients with severe hypertriglyceridemia (ie, triglyceride levels >1770 mg/dL).⁴ Data on the prevalence of other variants of xanthoma are lacking.

Diagnosis of eruptive xanthoma can be confirmed by skin biopsy if other conditions in the differential diagnosis can’t be ruled out or if the lesions do not resolve with treatment.

Eruptive xanthoma is characterized by an abrupt onset of crops of multiple yellowish to brownish papules that can coalesce into small plaques. The lesions can be generalized, but tend to be more densely distributed on the extensor surfaces of the arms and legs, buttocks, and thighs.⁵ Eruptive xanthoma often is associated with hypertriglyceridemia, which can be primary—as a result of a genetic defect caused by familial hypertriglyceridemia—or secondary, associated with poorly controlled diabetes mellitus, morbid obesity, excessive alcohol consumption, nephrotic syndrome, hypothyroidism, primary biliary cholangitis, and drugs like estrogen replacement therapies, corticosteroids, and isotretinoin.⁶ Pruritus and tenderness may or may not be present, and the Köbner phenomenon may occur.⁷

Continue to: The differential diagnosis

The differential diagnosis for eruptive xanthoma includes xanthoma disseminatum, non–Langerhans cell histiocytoses (eg, generalized eruptive histiocytosis), and cutaneous mastocytosis.¹

Xanthoma disseminatum is an extremely rare, but benign, disorder of non–Langerhans cell origin. The average age of onset is older than 40 years. The rash consists of multiple red-yellow papules and nodules that most commonly present in flexural areas. Forty percent to 60% of patients have mucosal involvement, and rarely the central nervous system is involved.⁸

Generalized eruptive histiocytosis is another rare non–Langerhans cell histiocytosis that occurs mainly in adults and is characterized by widespread, symmetric, red-brown papules on the trunk, arms, and legs, and rarely the mucous membranes.⁹

Cutaneous mastocytosis, especially xanthelasmoid mastocytosis, consists of multiple pruritic, yellowish, papular or nodular lesions that may mimic eruptive xanthoma. It occurs mainly in children and rarely in adults.¹⁰

Confirming the diagnosis, initiating treatment

The diagnosis of eruptive xanthoma can be confirmed by skin biopsy if other differential diagnoses cannot be ruled out or the lesions do not resolve with treatment. Skin biopsy will reveal lipid-laden macrophages (known as foam cells) deposited in the dermis.⁷

Continue to: Treatment of eruptive xanthoma

Treatment of eruptive xanthoma involves management of the underlying causes of the condition. In most cases, dietary control, intensive triglyceride-lowering therapies, and treatment of other secondary causes of hypertriglyceridemia result in complete resolution of the lesions within several weeks.⁵

Our patient’s outcome

Our patient’s sudden-onset rash alerted us to the presence of type 2 diabetes mellitus, hypertriglyceridemia, and heavy proteinuria, which he was not aware of previously. We counselled him about stringent low-sugar, low-lipid diet control and exercise, and we started him on metformin and gemfibrozil. He was referred to an internal medicine specialist for further assessment and management of his severe hypertriglyceridemia and heavy proteinuria.

Eruptive xanthoma may be an indicator of severe hypertriglyceri- demia, which can be associated with an increased risk for acute pancreatitis.

The rash started to wane 1 month after the patient started the metformin and gemfibrozil, and his drug regimen was changed to combination therapy with metformin/glimepiride and fenofibrate/simvastatin 6 weeks later when he was seen in the medical specialty clinic. Fundus photography performed 1 month after starting oral antidiabetic therapy showed no diabetic retinopathy or lipemia retinalis.

After 3 months of treatment, his serum triglycerides and hemoglobin A1c levels dropped to 3.8 mmol/L and 8.7%, respectively. The rash also resolved considerably, with only residual papules on the abdomen. This rapid clinical response to treatment of the underlying hypertriglyceridemia and diabetes further supported the clinical diagnosis of eruptive xanthoma.

THE TAKEAWAY

Eruptive xanthoma is relatively rare, but it is important for family physicians to recognize this clinical presentation as a potential indicator of severe hypertriglyceridemia. Recognizing hypertriglyceridemia early is important, as it can be associated with an increased risk for acute pancreatitis. Moreover, eruptive xanthoma might be the sole presenting symptom of underlying diabetes mellitus or familial hyperlipidemia, both of which can lead to a significant increase in cardiovascular risk if uncontrolled.

CORRESPONDENCE
Chan Kam Sum, MBChB, FRACGP, Tseung Kwan O Jockey Club General Out-patient Clinic, 99 Po Lam Road North, G/F, Tseung Kwan O, Kowloon, Hong Kong; [email protected]

THE CASE

A 37-year-old man presented with a sudden-onset, nonpruritic, nonpainful, papular rash of 1 month’s duration on his trunk and both arms and legs. Two weeks prior to the current presentation, he consulted a general practitioner, who treated the rash with a course of unknown oral antibiotics; the patient showed no improvement. He recalled that on a few occasions, he used his fingers to express a creamy discharge from some of the lesions. This temporarily reduced the size of those papules.

His medical history was unremarkable except for morbid obesity. He did not drink alcohol regularly and was not taking any medications prior to the onset of the rash. He had no family history of hyperlipidemia, but his mother had a history of diabetes mellitus.

Physical examination showed numerous discrete erythematous papules with a creamy center on his trunk and his arms and legs. The lesions were more numerous on the extensor surfaces of the arms and legs. Some of the papules coalesced to form small plaques (FIGURE). There was no scaling, and the lesions were firm in texture. The patient’s face was spared, and there was no mucosal involvement. The patient was otherwise systemically well.

THE DIAGNOSIS

Based on the morphology, distribution, and abrupt onset of the diffuse nonpruritic papules in this morbidly obese (but otherwise systemically well) middle-aged man, a clinical diagnosis of eruptive xanthoma was suspected. Subsequent blood testing revealed an elevated serum triglyceride level of 47.8 mmol/L (reference range, <1.7 mmol/L), elevated serum total cholesterol of 7.1 mmol/L (reference range, <6.2 mmol/L), and low serum high-density lipoprotein cholesterol of 0.7 mmol/L (reference range, >1 mmol/L in men). He also had an elevated fasting serum glucose level of 12.9 mmol/L (reference range, 3.9–5.6 mmol/L) and an elevated hemoglobin A1c (glycated hemoglobin) level of 10.9%.

Subsequent thyroid, liver, and renal function tests were normal, but the patient had heavy proteinuria, with an elevated urine albumin-to-creatinine ratio of 355.6 mg/mmol (reference range, ≤2.5 mg/mmol). The patient was referred to a dermatologist, who confirmed the clinical diagnosis without the need for a skin biopsy.

DISCUSSION

Xanthomas are lipid deposits in the skin and subcutaneous tissues that arise in the setting of hyperlipidemia and are caused by underlying familial or acquired disorders. Xanthomas associated with dyslipidemias include eruptive xanthoma, tendinous xanthoma, xanthoma palpebrarum, and xanthoma tuberosum (TABLE).^1-3 Other non–dyslipidemia-related xanthomas include xanthoma planum, xanthoma disseminatum, linear palmar xanthomas, and verrucous xanthoma. One retrospective cohort study reported an 8.5% (8/95) prevalence of eruptive xanthomas in patients with severe hypertriglyceridemia (ie, triglyceride levels >1770 mg/dL).⁴ Data on the prevalence of other variants of xanthoma are lacking.

Diagnosis of eruptive xanthoma can be confirmed by skin biopsy if other conditions in the differential diagnosis can’t be ruled out or if the lesions do not resolve with treatment.

Eruptive xanthoma is characterized by an abrupt onset of crops of multiple yellowish to brownish papules that can coalesce into small plaques. The lesions can be generalized, but tend to be more densely distributed on the extensor surfaces of the arms and legs, buttocks, and thighs.⁵ Eruptive xanthoma often is associated with hypertriglyceridemia, which can be primary—as a result of a genetic defect caused by familial hypertriglyceridemia—or secondary, associated with poorly controlled diabetes mellitus, morbid obesity, excessive alcohol consumption, nephrotic syndrome, hypothyroidism, primary biliary cholangitis, and drugs like estrogen replacement therapies, corticosteroids, and isotretinoin.⁶ Pruritus and tenderness may or may not be present, and the Köbner phenomenon may occur.⁷

Continue to: The differential diagnosis

The differential diagnosis for eruptive xanthoma includes xanthoma disseminatum, non–Langerhans cell histiocytoses (eg, generalized eruptive histiocytosis), and cutaneous mastocytosis.¹

Xanthoma disseminatum is an extremely rare, but benign, disorder of non–Langerhans cell origin. The average age of onset is older than 40 years. The rash consists of multiple red-yellow papules and nodules that most commonly present in flexural areas. Forty percent to 60% of patients have mucosal involvement, and rarely the central nervous system is involved.⁸

Generalized eruptive histiocytosis is another rare non–Langerhans cell histiocytosis that occurs mainly in adults and is characterized by widespread, symmetric, red-brown papules on the trunk, arms, and legs, and rarely the mucous membranes.⁹

Cutaneous mastocytosis, especially xanthelasmoid mastocytosis, consists of multiple pruritic, yellowish, papular or nodular lesions that may mimic eruptive xanthoma. It occurs mainly in children and rarely in adults.¹⁰

Confirming the diagnosis, initiating treatment

The diagnosis of eruptive xanthoma can be confirmed by skin biopsy if other differential diagnoses cannot be ruled out or the lesions do not resolve with treatment. Skin biopsy will reveal lipid-laden macrophages (known as foam cells) deposited in the dermis.⁷

Continue to: Treatment of eruptive xanthoma

Treatment of eruptive xanthoma involves management of the underlying causes of the condition. In most cases, dietary control, intensive triglyceride-lowering therapies, and treatment of other secondary causes of hypertriglyceridemia result in complete resolution of the lesions within several weeks.⁵

Our patient’s outcome

Our patient’s sudden-onset rash alerted us to the presence of type 2 diabetes mellitus, hypertriglyceridemia, and heavy proteinuria, which he was not aware of previously. We counselled him about stringent low-sugar, low-lipid diet control and exercise, and we started him on metformin and gemfibrozil. He was referred to an internal medicine specialist for further assessment and management of his severe hypertriglyceridemia and heavy proteinuria.

Eruptive xanthoma may be an indicator of severe hypertriglyceri- demia, which can be associated with an increased risk for acute pancreatitis.

The rash started to wane 1 month after the patient started the metformin and gemfibrozil, and his drug regimen was changed to combination therapy with metformin/glimepiride and fenofibrate/simvastatin 6 weeks later when he was seen in the medical specialty clinic. Fundus photography performed 1 month after starting oral antidiabetic therapy showed no diabetic retinopathy or lipemia retinalis.

After 3 months of treatment, his serum triglycerides and hemoglobin A1c levels dropped to 3.8 mmol/L and 8.7%, respectively. The rash also resolved considerably, with only residual papules on the abdomen. This rapid clinical response to treatment of the underlying hypertriglyceridemia and diabetes further supported the clinical diagnosis of eruptive xanthoma.

THE TAKEAWAY

Eruptive xanthoma is relatively rare, but it is important for family physicians to recognize this clinical presentation as a potential indicator of severe hypertriglyceridemia. Recognizing hypertriglyceridemia early is important, as it can be associated with an increased risk for acute pancreatitis. Moreover, eruptive xanthoma might be the sole presenting symptom of underlying diabetes mellitus or familial hyperlipidemia, both of which can lead to a significant increase in cardiovascular risk if uncontrolled.

CORRESPONDENCE
Chan Kam Sum, MBChB, FRACGP, Tseung Kwan O Jockey Club General Out-patient Clinic, 99 Po Lam Road North, G/F, Tseung Kwan O, Kowloon, Hong Kong; [email protected]

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

[email protected]

SOURCE: Murrell D et al. AAD 2019, Session S034.

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

[email protected]

SOURCE: Murrell D et al. AAD 2019, Session S034.

WASHINGTON – An investigational molecule that blocks the downstream proinflammatory effects of B cells controlled disease activity and induced clinical remission in patients with pemphigus by 12 weeks.

At the end of a 24-week, open-label trial, patients taking the oral inhibitor of Bruton tyrosine kinase (BTK) plus very-low-dose prednisone also experienced a mean 65% reduction in antidesmoglein antibodies, a key driver of the sometimes-fatal blistering disease, Deedee Murrell, MD, said at the annual meeting of the American Academy of Dermatology.

The clinical efficacy plus a favorable safety profile supports the further development of the molecule, designed and manufactured by Principia Biopharma in San Francisco. The company is currently recruiting for a pivotal phase 3 trial of PRN1008 in 120 patients with moderate to severe pemphigus vulgaris.

Despite the recent approval of rituximab (Rituxan) for moderate to severe pemphigus, there remains an unmet need for a quick-acting, steroid-sparing, anti-inflammatory treatment, said Dr. Murrell, professor and head of the department of dermatology at the University of New South Wales, Sydney.

“We need something to use instead of high-dose steroids while we are waiting for rituximab to kick in, which can take 3 months,” and rituximab, which depletes B cells, puts patients at risk for infection, she said. “We need something that has rapid onset, is steroid sparing, safe for chronic administration, avoids B-cell depletion, and is convenient.”

Blocking the BTK receptor on B cells puts the brakes on the B-cell mediated inflammatory pathway, preventing activation of monocytes, macrophages, mast cells, basophils, and neutrophils. At the same time, however, it does not deplete the B-cell population, said Dr. Murrell, the lead investigator.

The BELIEVE study comprised 27 patients with mild to severe pemphigus of an average 6 years’ duration. Most (18) had relapsing disease; the remainder had newly diagnosed pemphigus. A majority (16) had severe disease, as measured by a score of 15 or more on the Pemphigus Disease Activity Index (PDAI). Almost all (23) were positive for antidesmoglein antibodies. Only one patient was negative for antibodies.

The mean corticosteroid dose at baseline was 14 mg/day, although that ranged from no steroids to 30 mg/day.

The study consisted of a 12-week treatment phase and a 12-week follow-up phase. During treatment, patients could take no more than 0.5 mg/kg of prednisone daily, although with 400 mg PRN1008 twice a day. They were allowed to undertake rescue immunosuppression if they experienced a disease flare.

The primary endpoint was disease control by day 29 as evidenced by no new lesions. Secondary endpoints were complete remission, minimization of prednisone, quality of life, antibody levels, and clinician measures including the PDAI and the Autoimmune Bullous Skin Disorder Intensity Score.

By the end of week 4, 54% of patients had achieved the primary endpoint. The benefit continued to expand, with 73% reaching that response by the end of week 12. During this period, the mean prednisone dose was 12 mg/day.

Among the 24 patients who completed the study, complete remission occurred in 17% by week 12. However, patients continued to respond through the follow-up period, even after the study medication was stopped. By week 24, 25% of these patients experienced a complete remission. At the point of remission, the mean steroid dose was 8 mg/day. The median duration of remission was 2 months after stopping PRN1008.

The PDAI fell by a median of 70% by week 12 and was maintained at that level by the end of week 24. The median level of antidesmoglein autoantibodies fell by up to 65%. Again, the improvement continued throughout the off-drug follow-up period. In subgroup analyses, PRN1008 was more effective in patients with moderate to severe disease than those with mild disease (80% response vs. 64%). It was equally effective in those with newly diagnosed disease (75% vs. 72%) and regardless of antibody level at baseline.

The adverse event profile was relatively benign. Most side effects were mild and transient, and included upper abdominal pain, headache, and nausea. There were two mild infections and one serious infection, which presented in a patient with a long-standing localized cellulitis that activated and was associated a high fever. It was culture negative and PRN1008 was restarted without issue.

There was also one serious adverse event and one death, both unrelated to the study drug. One patient developed a pancreatic cyst that was discovered on day 29. The patient dropped out of the study to have elective surgery. The death occurred in a patient who developed acute respiratory failure on day 8 of treatment, caused by an undiagnosed congenital pulmonary sequestration. The patient died of a brain embolism shortly after lung surgery.

Dr. Murrell designed the study and was an investigator. She reported a financial relationship with Principia, as well as with numerous other pharmaceutical companies.

[email protected]

SOURCE: Murrell D et al. AAD 2019, Session S034.

A head-to-head comparison of four commonly used field-directed treatments for actinic keratosis (AK) found that 5% fluorouracil cream was the most effective at reducing the size of lesions.

pedrojperez/Getty Images

In a study published in the March 7 issue of the New England Journal of Medicine, researchers reported the outcomes of a multicenter, single-blind trial in 602 patients with five or more AK lesions in one continuous area on the head measuring 25-100 cm². Patients were randomized to treatment with either 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel.

Overall, 74.7% of patients who received fluorouracil cream achieved treatment success – defined as at least a 75% reduction in lesion size at 12 months after the end of treatment – compared with 53.9% of patients treated with imiquimod, 37.7% of those treated with MAL-PDT, and 28.9% of those treated with ingenol mebutate. The differences between fluorouracil and the other treatments was significant.

Maud H.E. Jansen, MD, and Janneke P.H.M. Kessels, MD, of the department of dermatology at Maastricht (the Netherlands) University Medical Center and their coauthors pointed out that, while there was plenty of literature about different AK treatments, there were few head-to-head comparisons and many studies were underpowered or had different outcome measures.

Even when the analysis was restricted to patients with grade I or II lesions, fluorouracil remained the most effective treatment, with 75.3% of patients achieving treatment success, compared with 52.6% with imiquimod, 38.7% with MAL-PDT, and 30.2% with ingenol mebutate.

There were not enough patients with more severe grade III lesions to enable a separate analysis of their outcomes; 49 (7.9%) of patients in the study had at least one grade III lesion.

The authors noted that many previous studies had excluded patients with grade III lesions. “Exclusion of patients with grade III lesions was associated with slightly higher rates of success in the fluorouracil, MAL-PDT, and ingenol mebutate groups than the rates in the unrestricted analysis,” they wrote. The inclusion of patients with grade III AK lesions in this trial made it “more representative of patients seen in daily practice,” they added.

Treatment failure – less than 75% clearance of actinic keratosis at 3 months after the final treatment – was seen after one treatment cycle in 14.8% of patients treated with fluorouracil, 37.2% of patients on imiquimod, 34.6% of patients given photodynamic therapy, and 47.8% of patients on ingenol mebutate therapy.

All these patients were offered a second treatment cycle, but those treated with imiquimod, PDT, and ingenol mebutate were less likely to undergo a second treatment.

A head-to-head comparison of four commonly used field-directed treatments for actinic keratosis (AK) found that 5% fluorouracil cream was the most effective at reducing the size of lesions.

pedrojperez/Getty Images

In a study published in the March 7 issue of the New England Journal of Medicine, researchers reported the outcomes of a multicenter, single-blind trial in 602 patients with five or more AK lesions in one continuous area on the head measuring 25-100 cm². Patients were randomized to treatment with either 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel.

Overall, 74.7% of patients who received fluorouracil cream achieved treatment success – defined as at least a 75% reduction in lesion size at 12 months after the end of treatment – compared with 53.9% of patients treated with imiquimod, 37.7% of those treated with MAL-PDT, and 28.9% of those treated with ingenol mebutate. The differences between fluorouracil and the other treatments was significant.

Maud H.E. Jansen, MD, and Janneke P.H.M. Kessels, MD, of the department of dermatology at Maastricht (the Netherlands) University Medical Center and their coauthors pointed out that, while there was plenty of literature about different AK treatments, there were few head-to-head comparisons and many studies were underpowered or had different outcome measures.

Even when the analysis was restricted to patients with grade I or II lesions, fluorouracil remained the most effective treatment, with 75.3% of patients achieving treatment success, compared with 52.6% with imiquimod, 38.7% with MAL-PDT, and 30.2% with ingenol mebutate.

There were not enough patients with more severe grade III lesions to enable a separate analysis of their outcomes; 49 (7.9%) of patients in the study had at least one grade III lesion.

The authors noted that many previous studies had excluded patients with grade III lesions. “Exclusion of patients with grade III lesions was associated with slightly higher rates of success in the fluorouracil, MAL-PDT, and ingenol mebutate groups than the rates in the unrestricted analysis,” they wrote. The inclusion of patients with grade III AK lesions in this trial made it “more representative of patients seen in daily practice,” they added.

Treatment failure – less than 75% clearance of actinic keratosis at 3 months after the final treatment – was seen after one treatment cycle in 14.8% of patients treated with fluorouracil, 37.2% of patients on imiquimod, 34.6% of patients given photodynamic therapy, and 47.8% of patients on ingenol mebutate therapy.

All these patients were offered a second treatment cycle, but those treated with imiquimod, PDT, and ingenol mebutate were less likely to undergo a second treatment.

A head-to-head comparison of four commonly used field-directed treatments for actinic keratosis (AK) found that 5% fluorouracil cream was the most effective at reducing the size of lesions.

pedrojperez/Getty Images

In a study published in the March 7 issue of the New England Journal of Medicine, researchers reported the outcomes of a multicenter, single-blind trial in 602 patients with five or more AK lesions in one continuous area on the head measuring 25-100 cm². Patients were randomized to treatment with either 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel.

Overall, 74.7% of patients who received fluorouracil cream achieved treatment success – defined as at least a 75% reduction in lesion size at 12 months after the end of treatment – compared with 53.9% of patients treated with imiquimod, 37.7% of those treated with MAL-PDT, and 28.9% of those treated with ingenol mebutate. The differences between fluorouracil and the other treatments was significant.

Maud H.E. Jansen, MD, and Janneke P.H.M. Kessels, MD, of the department of dermatology at Maastricht (the Netherlands) University Medical Center and their coauthors pointed out that, while there was plenty of literature about different AK treatments, there were few head-to-head comparisons and many studies were underpowered or had different outcome measures.

Even when the analysis was restricted to patients with grade I or II lesions, fluorouracil remained the most effective treatment, with 75.3% of patients achieving treatment success, compared with 52.6% with imiquimod, 38.7% with MAL-PDT, and 30.2% with ingenol mebutate.

There were not enough patients with more severe grade III lesions to enable a separate analysis of their outcomes; 49 (7.9%) of patients in the study had at least one grade III lesion.

The authors noted that many previous studies had excluded patients with grade III lesions. “Exclusion of patients with grade III lesions was associated with slightly higher rates of success in the fluorouracil, MAL-PDT, and ingenol mebutate groups than the rates in the unrestricted analysis,” they wrote. The inclusion of patients with grade III AK lesions in this trial made it “more representative of patients seen in daily practice,” they added.

Treatment failure – less than 75% clearance of actinic keratosis at 3 months after the final treatment – was seen after one treatment cycle in 14.8% of patients treated with fluorouracil, 37.2% of patients on imiquimod, 34.6% of patients given photodynamic therapy, and 47.8% of patients on ingenol mebutate therapy.

All these patients were offered a second treatment cycle, but those treated with imiquimod, PDT, and ingenol mebutate were less likely to undergo a second treatment.

The FP suspected that this was a skin cancer with ulceration and pigmentation. The differential diagnosis included pigmented basal cell carcinoma, melanoma, and squamous cell carcinoma. If this were a melanoma, there would appear to be areas of regression between the islands of pigmentation. The FP explained that a biopsy was needed and suggested a broad shave biopsy because this technique would provide adequate tissue to the pathologist. (See the Watch & Learn video on “Shave biopsy.”)

The FP performed the broad shave biopsy and saw some remaining pigment at the base of the initial cut. He performed a second pass with the DermaBlade and explained this in the pathology requisition. (It is acceptable to send a deeper section of tissue if it appears that there is some remaining tumor below the initial biopsy.)

The biopsy report revealed lentigo maligna melanoma, which was approximately 2 mm thick—much deeper than the clinical appearance suggested. The pathologist combined the depths from the 2 specimens to get an approximate Breslow level. In this case, the most important information was that this was >1 mm in depth, which suggested that a sentinel lymph node biopsy would be needed for prognostic information. The patient was referred to Surgical Oncology for wide excision and sentinel lymph node biopsy.

Fortunately, the nodes were negative for metastasis. The wide excision was closed with a graft that healed well over time. The patient was followed with regular skin exams and careful lymph node exams of the neck and supraclavicular areas. He now wears a hat whenever he is outdoors.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was a skin cancer with ulceration and pigmentation. The differential diagnosis included pigmented basal cell carcinoma, melanoma, and squamous cell carcinoma. If this were a melanoma, there would appear to be areas of regression between the islands of pigmentation. The FP explained that a biopsy was needed and suggested a broad shave biopsy because this technique would provide adequate tissue to the pathologist. (See the Watch & Learn video on “Shave biopsy.”)

The FP performed the broad shave biopsy and saw some remaining pigment at the base of the initial cut. He performed a second pass with the DermaBlade and explained this in the pathology requisition. (It is acceptable to send a deeper section of tissue if it appears that there is some remaining tumor below the initial biopsy.)

The biopsy report revealed lentigo maligna melanoma, which was approximately 2 mm thick—much deeper than the clinical appearance suggested. The pathologist combined the depths from the 2 specimens to get an approximate Breslow level. In this case, the most important information was that this was >1 mm in depth, which suggested that a sentinel lymph node biopsy would be needed for prognostic information. The patient was referred to Surgical Oncology for wide excision and sentinel lymph node biopsy.

Fortunately, the nodes were negative for metastasis. The wide excision was closed with a graft that healed well over time. The patient was followed with regular skin exams and careful lymph node exams of the neck and supraclavicular areas. He now wears a hat whenever he is outdoors.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP suspected that this was a skin cancer with ulceration and pigmentation. The differential diagnosis included pigmented basal cell carcinoma, melanoma, and squamous cell carcinoma. If this were a melanoma, there would appear to be areas of regression between the islands of pigmentation. The FP explained that a biopsy was needed and suggested a broad shave biopsy because this technique would provide adequate tissue to the pathologist. (See the Watch & Learn video on “Shave biopsy.”)

The FP performed the broad shave biopsy and saw some remaining pigment at the base of the initial cut. He performed a second pass with the DermaBlade and explained this in the pathology requisition. (It is acceptable to send a deeper section of tissue if it appears that there is some remaining tumor below the initial biopsy.)

The biopsy report revealed lentigo maligna melanoma, which was approximately 2 mm thick—much deeper than the clinical appearance suggested. The pathologist combined the depths from the 2 specimens to get an approximate Breslow level. In this case, the most important information was that this was >1 mm in depth, which suggested that a sentinel lymph node biopsy would be needed for prognostic information. The patient was referred to Surgical Oncology for wide excision and sentinel lymph node biopsy.

Fortunately, the nodes were negative for metastasis. The wide excision was closed with a graft that healed well over time. The patient was followed with regular skin exams and careful lymph node exams of the neck and supraclavicular areas. He now wears a hat whenever he is outdoors.

‌

Photo courtesy of Jonathan Karnes, MD and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1103-1111.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Comorbid dermatologic conditions appear to be common in children with lichen nitidus, as is generalized disease, according to Selcen Kundak, MD, and Yasemin Çakır, MD, of Dr. Behcet Uz Children’s Research and Training Hospital in Izmir, Turkey.

In a retrospective study 10-year study of 17 children with biopsy-confirmed lichen nitidus (LN) who were diagnosed with the disease at a single tertiary care health center between January 2007 and March 2017, the mean age of onset was 9 years and 15 of 17 (88%) were male. The mean skin lesion duration period was 13 months (range 1-48 months).

The generalized form of LN was common in the study population, occurring in 7 of 17 (41%) patients, 2 of whom had severe pruritus. Comorbid skin conditions also occurred in seven (41%) patients; these conditions included lichen planus in one patient, lichen striatus in one patient, nail psoriasis in one patients, and cutaneous features of atopic skin in four patients. In addition, 11 of 17 (65%) patients had multinucleated giant cells.

“Seven of 17 had comorbid skin conditions. Lichen planus, lichen striatus, psoriasis, and atopy are also chronic inflammatory skin conditions, and possibly, there are common triggers for these and LN; however, this is speculative, not proven,” the investigators concluded in Pediatric Dermatology.

Mild to moderate corticosteroids were give to 16 patients; all showed some clinical improvement within 3 weeks. One patient was treated with systemic corticosteroids.

The study authors reported no relevant financial disclosures.

[email protected]

SOURCE: Kundak S et al. Pediatr Dermatol. 2019 Feb 11. doi: 10.1111/pde.13749.

Comorbid dermatologic conditions appear to be common in children with lichen nitidus, as is generalized disease, according to Selcen Kundak, MD, and Yasemin Çakır, MD, of Dr. Behcet Uz Children’s Research and Training Hospital in Izmir, Turkey.

In a retrospective study 10-year study of 17 children with biopsy-confirmed lichen nitidus (LN) who were diagnosed with the disease at a single tertiary care health center between January 2007 and March 2017, the mean age of onset was 9 years and 15 of 17 (88%) were male. The mean skin lesion duration period was 13 months (range 1-48 months).

The generalized form of LN was common in the study population, occurring in 7 of 17 (41%) patients, 2 of whom had severe pruritus. Comorbid skin conditions also occurred in seven (41%) patients; these conditions included lichen planus in one patient, lichen striatus in one patient, nail psoriasis in one patients, and cutaneous features of atopic skin in four patients. In addition, 11 of 17 (65%) patients had multinucleated giant cells.

“Seven of 17 had comorbid skin conditions. Lichen planus, lichen striatus, psoriasis, and atopy are also chronic inflammatory skin conditions, and possibly, there are common triggers for these and LN; however, this is speculative, not proven,” the investigators concluded in Pediatric Dermatology.

Mild to moderate corticosteroids were give to 16 patients; all showed some clinical improvement within 3 weeks. One patient was treated with systemic corticosteroids.

The study authors reported no relevant financial disclosures.

[email protected]

SOURCE: Kundak S et al. Pediatr Dermatol. 2019 Feb 11. doi: 10.1111/pde.13749.

Comorbid dermatologic conditions appear to be common in children with lichen nitidus, as is generalized disease, according to Selcen Kundak, MD, and Yasemin Çakır, MD, of Dr. Behcet Uz Children’s Research and Training Hospital in Izmir, Turkey.

In a retrospective study 10-year study of 17 children with biopsy-confirmed lichen nitidus (LN) who were diagnosed with the disease at a single tertiary care health center between January 2007 and March 2017, the mean age of onset was 9 years and 15 of 17 (88%) were male. The mean skin lesion duration period was 13 months (range 1-48 months).

The generalized form of LN was common in the study population, occurring in 7 of 17 (41%) patients, 2 of whom had severe pruritus. Comorbid skin conditions also occurred in seven (41%) patients; these conditions included lichen planus in one patient, lichen striatus in one patient, nail psoriasis in one patients, and cutaneous features of atopic skin in four patients. In addition, 11 of 17 (65%) patients had multinucleated giant cells.

“Seven of 17 had comorbid skin conditions. Lichen planus, lichen striatus, psoriasis, and atopy are also chronic inflammatory skin conditions, and possibly, there are common triggers for these and LN; however, this is speculative, not proven,” the investigators concluded in Pediatric Dermatology.

Mild to moderate corticosteroids were give to 16 patients; all showed some clinical improvement within 3 weeks. One patient was treated with systemic corticosteroids.

The study authors reported no relevant financial disclosures.

[email protected]

SOURCE: Kundak S et al. Pediatr Dermatol. 2019 Feb 11. doi: 10.1111/pde.13749.

SAN FRANCISCO – Children diagnosed with atopic dermatitis when they were 1 year old were significantly more likely to have active food allergies and to have those allergies persist throughout childhood to age 18 years, based on findings from a prospective, longitudinal study of 287 Wisconsin children.

Mitchel L. Zoler/MDedge News

The link between atopic dermatitis (AD) and food allergy was especially strong in children who displayed early and recurrent AD; the link was weaker or essentially nonexistent for children with early transient AD or AD that first appeared later in childhood, Anne Marie Singh, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results also showed that even mild AD linked with an increased prevalence of food allergy when it appeared early and persisted, but more severe AD with this onset and recurrence pattern led to an even greater prevalence of food allergy, said Dr. Singh, a pediatric allergist and asthma specialist at the University of Wisconsin–Madison.

“The data suggest that something about early, recurrent AD increases the risk for food allergy throughout childhood,” Dr. Singh said in an interview. The findings suggest that surveillance for food allergies need to be intensified in infants who present with AD by the time they’re 1 year old and that food allergy surveillance should continue as these children age as long as their AD recurs.

The results also hint that these children might potentially benefit from steps aimed at desensitizing the allergy, although this must be proven in a future intervention study, she said.

The results suggest that a food allergy prevention regimen like the one used in the Learning Early About Peanut Allergy (LEAP) trial (New Engl J Med. 2015 Feb 26;372[9]:803-13) to prevent peanut allergy may be appropriate for selected, high-risk children with early AD, but this hypothesis needs testing, Dr. Singh said. She noted that some important differences exist between the patients enrolled in LEAP and the children studied in the current report: In LEAP, all enrolled children had severe eczema, an established egg allergy, or both. The findings reported by Dr. Singh came from children with AD, but only about 30% had moderate or severe eczema, and her analysis did not subdivide the observed food allergies by the type of food that caused a reaction.

She and her associates used data collected in the Childhood Origins of Asthma (COAST) study, begun in 1998, which enrolled 287 infants prior to birth who had at least one parent who was allergic, asthmatic, or both (Pediatr Allergy Immunol. 2002 Dec;13[s15]:38-43). The data showed that 62% of the infants had either no AD or transient AD, 14% had late onset AD, and 24% had early, recurrent AD. Although the data showed a statistically significant link between AD at 1 year old and food allergies throughout childhood, further analysis that broke the population into three different patterns of AD showed that the link with food allergy primarily existed among children with the early, recurrent form. Children with early, recurrent atopic dermatitis had a food allergy prevalence of 12%-27% annually through the age of 18 years.

“The data suggest that immunologic changes early in life are critical to food allergy development and that these changes have long-lasting effects throughout childhood,” Dr. Singh concluded. “The immunologic mechanisms by which early AD affects food allergy development and disease expression require further investigation.”

COAST received no commercial funding. Dr. Singh reported no relevant financial disclosures.

[email protected]

SOURCE: Singh AM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB125.

SAN FRANCISCO – Children diagnosed with atopic dermatitis when they were 1 year old were significantly more likely to have active food allergies and to have those allergies persist throughout childhood to age 18 years, based on findings from a prospective, longitudinal study of 287 Wisconsin children.

Mitchel L. Zoler/MDedge News

The link between atopic dermatitis (AD) and food allergy was especially strong in children who displayed early and recurrent AD; the link was weaker or essentially nonexistent for children with early transient AD or AD that first appeared later in childhood, Anne Marie Singh, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results also showed that even mild AD linked with an increased prevalence of food allergy when it appeared early and persisted, but more severe AD with this onset and recurrence pattern led to an even greater prevalence of food allergy, said Dr. Singh, a pediatric allergist and asthma specialist at the University of Wisconsin–Madison.

“The data suggest that something about early, recurrent AD increases the risk for food allergy throughout childhood,” Dr. Singh said in an interview. The findings suggest that surveillance for food allergies need to be intensified in infants who present with AD by the time they’re 1 year old and that food allergy surveillance should continue as these children age as long as their AD recurs.

The results also hint that these children might potentially benefit from steps aimed at desensitizing the allergy, although this must be proven in a future intervention study, she said.

The results suggest that a food allergy prevention regimen like the one used in the Learning Early About Peanut Allergy (LEAP) trial (New Engl J Med. 2015 Feb 26;372[9]:803-13) to prevent peanut allergy may be appropriate for selected, high-risk children with early AD, but this hypothesis needs testing, Dr. Singh said. She noted that some important differences exist between the patients enrolled in LEAP and the children studied in the current report: In LEAP, all enrolled children had severe eczema, an established egg allergy, or both. The findings reported by Dr. Singh came from children with AD, but only about 30% had moderate or severe eczema, and her analysis did not subdivide the observed food allergies by the type of food that caused a reaction.

She and her associates used data collected in the Childhood Origins of Asthma (COAST) study, begun in 1998, which enrolled 287 infants prior to birth who had at least one parent who was allergic, asthmatic, or both (Pediatr Allergy Immunol. 2002 Dec;13[s15]:38-43). The data showed that 62% of the infants had either no AD or transient AD, 14% had late onset AD, and 24% had early, recurrent AD. Although the data showed a statistically significant link between AD at 1 year old and food allergies throughout childhood, further analysis that broke the population into three different patterns of AD showed that the link with food allergy primarily existed among children with the early, recurrent form. Children with early, recurrent atopic dermatitis had a food allergy prevalence of 12%-27% annually through the age of 18 years.

“The data suggest that immunologic changes early in life are critical to food allergy development and that these changes have long-lasting effects throughout childhood,” Dr. Singh concluded. “The immunologic mechanisms by which early AD affects food allergy development and disease expression require further investigation.”

COAST received no commercial funding. Dr. Singh reported no relevant financial disclosures.

[email protected]

SOURCE: Singh AM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB125.

SAN FRANCISCO – Children diagnosed with atopic dermatitis when they were 1 year old were significantly more likely to have active food allergies and to have those allergies persist throughout childhood to age 18 years, based on findings from a prospective, longitudinal study of 287 Wisconsin children.

Mitchel L. Zoler/MDedge News

The link between atopic dermatitis (AD) and food allergy was especially strong in children who displayed early and recurrent AD; the link was weaker or essentially nonexistent for children with early transient AD or AD that first appeared later in childhood, Anne Marie Singh, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The results also showed that even mild AD linked with an increased prevalence of food allergy when it appeared early and persisted, but more severe AD with this onset and recurrence pattern led to an even greater prevalence of food allergy, said Dr. Singh, a pediatric allergist and asthma specialist at the University of Wisconsin–Madison.

“The data suggest that something about early, recurrent AD increases the risk for food allergy throughout childhood,” Dr. Singh said in an interview. The findings suggest that surveillance for food allergies need to be intensified in infants who present with AD by the time they’re 1 year old and that food allergy surveillance should continue as these children age as long as their AD recurs.

The results also hint that these children might potentially benefit from steps aimed at desensitizing the allergy, although this must be proven in a future intervention study, she said.

The results suggest that a food allergy prevention regimen like the one used in the Learning Early About Peanut Allergy (LEAP) trial (New Engl J Med. 2015 Feb 26;372[9]:803-13) to prevent peanut allergy may be appropriate for selected, high-risk children with early AD, but this hypothesis needs testing, Dr. Singh said. She noted that some important differences exist between the patients enrolled in LEAP and the children studied in the current report: In LEAP, all enrolled children had severe eczema, an established egg allergy, or both. The findings reported by Dr. Singh came from children with AD, but only about 30% had moderate or severe eczema, and her analysis did not subdivide the observed food allergies by the type of food that caused a reaction.

She and her associates used data collected in the Childhood Origins of Asthma (COAST) study, begun in 1998, which enrolled 287 infants prior to birth who had at least one parent who was allergic, asthmatic, or both (Pediatr Allergy Immunol. 2002 Dec;13[s15]:38-43). The data showed that 62% of the infants had either no AD or transient AD, 14% had late onset AD, and 24% had early, recurrent AD. Although the data showed a statistically significant link between AD at 1 year old and food allergies throughout childhood, further analysis that broke the population into three different patterns of AD showed that the link with food allergy primarily existed among children with the early, recurrent form. Children with early, recurrent atopic dermatitis had a food allergy prevalence of 12%-27% annually through the age of 18 years.

“The data suggest that immunologic changes early in life are critical to food allergy development and that these changes have long-lasting effects throughout childhood,” Dr. Singh concluded. “The immunologic mechanisms by which early AD affects food allergy development and disease expression require further investigation.”

COAST received no commercial funding. Dr. Singh reported no relevant financial disclosures.

[email protected]

SOURCE: Singh AM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB125.

WASHINGTON – The role of food allergies in atopic dermatitis (AD) is an important issue for both patients and their clinicians and brings up an interesting discussion, Peter Lio, MD, said in a video interview at the annual meeting of the American Academy of Dermatology.

Patients are often convinced that food is the main driver of their AD, or parents believe it is a trigger in their children with AD, according to Dr. Lio of the departments of dermatology and pediatrics at Northwestern University, Chicago.

Vidyard Video

There is an increased risk of true food allergy in patients with AD, which “seems to get worse with increasing severity of the disease,” he pointed out. However, he added, many patients believe that food allergy is what is driving their eczema, “and that’s the part we don’t really think bears out” in clinical trials.

In the interview, Dr. Lio reviewed some of the clinical trial data and discussed other issues, including foods that seem to have an inflammatory effect in the body, the concepts of “transcutaneous sensitization” in children with AD and the “leaky gut,” and why he tends to recommend probiotics for patients with AD.

Dr. Lio spoke on diet and AD during a session titled “Dietary Triggers and Modifications of Common Dermatologic Conditions – An Evidence Based Approach,” at the meeting, He had no relevant disclosures.

[email protected]

WASHINGTON – The role of food allergies in atopic dermatitis (AD) is an important issue for both patients and their clinicians and brings up an interesting discussion, Peter Lio, MD, said in a video interview at the annual meeting of the American Academy of Dermatology.

Patients are often convinced that food is the main driver of their AD, or parents believe it is a trigger in their children with AD, according to Dr. Lio of the departments of dermatology and pediatrics at Northwestern University, Chicago.

Vidyard Video

There is an increased risk of true food allergy in patients with AD, which “seems to get worse with increasing severity of the disease,” he pointed out. However, he added, many patients believe that food allergy is what is driving their eczema, “and that’s the part we don’t really think bears out” in clinical trials.

In the interview, Dr. Lio reviewed some of the clinical trial data and discussed other issues, including foods that seem to have an inflammatory effect in the body, the concepts of “transcutaneous sensitization” in children with AD and the “leaky gut,” and why he tends to recommend probiotics for patients with AD.

Dr. Lio spoke on diet and AD during a session titled “Dietary Triggers and Modifications of Common Dermatologic Conditions – An Evidence Based Approach,” at the meeting, He had no relevant disclosures.

[email protected]

WASHINGTON – The role of food allergies in atopic dermatitis (AD) is an important issue for both patients and their clinicians and brings up an interesting discussion, Peter Lio, MD, said in a video interview at the annual meeting of the American Academy of Dermatology.

Patients are often convinced that food is the main driver of their AD, or parents believe it is a trigger in their children with AD, according to Dr. Lio of the departments of dermatology and pediatrics at Northwestern University, Chicago.

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There is an increased risk of true food allergy in patients with AD, which “seems to get worse with increasing severity of the disease,” he pointed out. However, he added, many patients believe that food allergy is what is driving their eczema, “and that’s the part we don’t really think bears out” in clinical trials.

In the interview, Dr. Lio reviewed some of the clinical trial data and discussed other issues, including foods that seem to have an inflammatory effect in the body, the concepts of “transcutaneous sensitization” in children with AD and the “leaky gut,” and why he tends to recommend probiotics for patients with AD.

Dr. Lio spoke on diet and AD during a session titled “Dietary Triggers and Modifications of Common Dermatologic Conditions – An Evidence Based Approach,” at the meeting, He had no relevant disclosures.

[email protected]

Poor sleep quality, but not sleep duration, was significantly associated with active atopic dermatitis in a longitudinal study of more than 13,000 children.

The itching associated with atopic dermatitis (AD) may interfere with children’s sleep, and sleep studies suggest that children with active disease are more restless at night, wrote Faustine D. Ramirez of the University of California, San Francisco, and her colleagues. Their report is in JAMA Pediatrics.

“Acute and chronic sleep disturbances have been associated with a wide range of cognitive, mood, and behavioral impairments and have been linked to poor educational performance,” the researchers noted.

To determine the impact of active AD on children’s sleep, the researchers reviewed data from 13,988 children followed for a median of 11 years. Of these, 4,938 children met the definition for AD between age 2 and 16 years.

Overall, children with active AD were approximately 50% more likely to experience poor sleep quality than were those without AD (adjusted odds ratio, 1.48). Sleep quality was even worse for children with severe active AD (aOR, 1.68), and active AD plus asthma or allergic rhinitis (aOR 2.15). Sleep quality was significantly worse in children reporting mild AD (aOR, 1.40) or inactive AD (aOR, 1.41), compared with children without AD. Nighttime sleep duration was similar throughout childhood for children with and without AD.

“In addition to increased nighttime awakenings and difficulty falling asleep, we found that children with active atopic dermatitis were more likely to report nightmares and early morning awakenings, which has not been previously studied,” Ms. Ramirez and her associates said.

Total sleep duration was statistically shorter overall for children with AD, compared with those without AD, but the difference was not clinically significant, they noted.

The participants were from a longitudinal study in the United Kingdom in which pregnant women were recruited between 1990 and 1992. For those with children alive at 1 year, their children were followed for approximately 16 years. Sleep quality was assessed at six time points with four standardized questionnaires between ages 2 and 10 years, and sleep duration was assessed at eight time points between ages 2 and 16 years with standardized questionnaires.

The study findings were limited by several factors, including some missing data and patient attrition, as well as possible misclassification bias because of the use of parent and patient self-reports, and a possible lack of generalizability to other populations, the researchers noted.

However, the results support the need for developing clinical outcome measures to address sleep quality in children with AD, they said. “Additional work should investigate interventions to improve sleep quality and examine the association between atopic dermatitis treatment and children’s sleep.”

The study was funded primarily by a grant from the National Eczema Association. Ms. Ramirez disclosed a grant from the National Institutes of Health. Two other investigators received grants, one from NIH and the other Wellcome Senior Clinical Fellowship in Science. One coauthor reported receiving multiple grants, as well as paid consulting for TARGETPharma, a company developing a prospective atopic dermatitis registry.

SOURCE: Ramirez FD al. JAMA Pediatr. 2019 Mar 4. doi: 10.1001/jamapediatrics.2019.0025.

Poor sleep quality, but not sleep duration, was significantly associated with active atopic dermatitis in a longitudinal study of more than 13,000 children.

The itching associated with atopic dermatitis (AD) may interfere with children’s sleep, and sleep studies suggest that children with active disease are more restless at night, wrote Faustine D. Ramirez of the University of California, San Francisco, and her colleagues. Their report is in JAMA Pediatrics.

“Acute and chronic sleep disturbances have been associated with a wide range of cognitive, mood, and behavioral impairments and have been linked to poor educational performance,” the researchers noted.

To determine the impact of active AD on children’s sleep, the researchers reviewed data from 13,988 children followed for a median of 11 years. Of these, 4,938 children met the definition for AD between age 2 and 16 years.

Overall, children with active AD were approximately 50% more likely to experience poor sleep quality than were those without AD (adjusted odds ratio, 1.48). Sleep quality was even worse for children with severe active AD (aOR, 1.68), and active AD plus asthma or allergic rhinitis (aOR 2.15). Sleep quality was significantly worse in children reporting mild AD (aOR, 1.40) or inactive AD (aOR, 1.41), compared with children without AD. Nighttime sleep duration was similar throughout childhood for children with and without AD.

“In addition to increased nighttime awakenings and difficulty falling asleep, we found that children with active atopic dermatitis were more likely to report nightmares and early morning awakenings, which has not been previously studied,” Ms. Ramirez and her associates said.

Total sleep duration was statistically shorter overall for children with AD, compared with those without AD, but the difference was not clinically significant, they noted.

The participants were from a longitudinal study in the United Kingdom in which pregnant women were recruited between 1990 and 1992. For those with children alive at 1 year, their children were followed for approximately 16 years. Sleep quality was assessed at six time points with four standardized questionnaires between ages 2 and 10 years, and sleep duration was assessed at eight time points between ages 2 and 16 years with standardized questionnaires.

The study findings were limited by several factors, including some missing data and patient attrition, as well as possible misclassification bias because of the use of parent and patient self-reports, and a possible lack of generalizability to other populations, the researchers noted.

However, the results support the need for developing clinical outcome measures to address sleep quality in children with AD, they said. “Additional work should investigate interventions to improve sleep quality and examine the association between atopic dermatitis treatment and children’s sleep.”

The study was funded primarily by a grant from the National Eczema Association. Ms. Ramirez disclosed a grant from the National Institutes of Health. Two other investigators received grants, one from NIH and the other Wellcome Senior Clinical Fellowship in Science. One coauthor reported receiving multiple grants, as well as paid consulting for TARGETPharma, a company developing a prospective atopic dermatitis registry.

SOURCE: Ramirez FD al. JAMA Pediatr. 2019 Mar 4. doi: 10.1001/jamapediatrics.2019.0025.

Poor sleep quality, but not sleep duration, was significantly associated with active atopic dermatitis in a longitudinal study of more than 13,000 children.

The itching associated with atopic dermatitis (AD) may interfere with children’s sleep, and sleep studies suggest that children with active disease are more restless at night, wrote Faustine D. Ramirez of the University of California, San Francisco, and her colleagues. Their report is in JAMA Pediatrics.

“Acute and chronic sleep disturbances have been associated with a wide range of cognitive, mood, and behavioral impairments and have been linked to poor educational performance,” the researchers noted.

To determine the impact of active AD on children’s sleep, the researchers reviewed data from 13,988 children followed for a median of 11 years. Of these, 4,938 children met the definition for AD between age 2 and 16 years.

Overall, children with active AD were approximately 50% more likely to experience poor sleep quality than were those without AD (adjusted odds ratio, 1.48). Sleep quality was even worse for children with severe active AD (aOR, 1.68), and active AD plus asthma or allergic rhinitis (aOR 2.15). Sleep quality was significantly worse in children reporting mild AD (aOR, 1.40) or inactive AD (aOR, 1.41), compared with children without AD. Nighttime sleep duration was similar throughout childhood for children with and without AD.

“In addition to increased nighttime awakenings and difficulty falling asleep, we found that children with active atopic dermatitis were more likely to report nightmares and early morning awakenings, which has not been previously studied,” Ms. Ramirez and her associates said.

Total sleep duration was statistically shorter overall for children with AD, compared with those without AD, but the difference was not clinically significant, they noted.

The participants were from a longitudinal study in the United Kingdom in which pregnant women were recruited between 1990 and 1992. For those with children alive at 1 year, their children were followed for approximately 16 years. Sleep quality was assessed at six time points with four standardized questionnaires between ages 2 and 10 years, and sleep duration was assessed at eight time points between ages 2 and 16 years with standardized questionnaires.

The study findings were limited by several factors, including some missing data and patient attrition, as well as possible misclassification bias because of the use of parent and patient self-reports, and a possible lack of generalizability to other populations, the researchers noted.

However, the results support the need for developing clinical outcome measures to address sleep quality in children with AD, they said. “Additional work should investigate interventions to improve sleep quality and examine the association between atopic dermatitis treatment and children’s sleep.”

The study was funded primarily by a grant from the National Eczema Association. Ms. Ramirez disclosed a grant from the National Institutes of Health. Two other investigators received grants, one from NIH and the other Wellcome Senior Clinical Fellowship in Science. One coauthor reported receiving multiple grants, as well as paid consulting for TARGETPharma, a company developing a prospective atopic dermatitis registry.

SOURCE: Ramirez FD al. JAMA Pediatr. 2019 Mar 4. doi: 10.1001/jamapediatrics.2019.0025.

WASHINGTON – The American Contact Dermatitis Society has selected isobornyl acrylate the contact allergen of the year. It is an acrylic monomer used as an adhesive.

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Among other applications, isobornyl acrylate is often used in medical devices. The selection was made based in part on multiple case reports of diabetes patients developing contact allergies to their diabetes devices, such as insulin pumps, explained Golara Honari, MD, of Stanford (Calif.) University, who presented the selection at the ACDS annual meeting.

The significance of this allergen is that testing through routine panels does not identify it, so clinician awareness is especially important, Dr. Honari noted in a video interview at the meeting.

Most of the reported contact allergen cases have been in patients with diabetes, but clinicians should think about other possible sources, such as acrylic nails, she said. As for treatment, clinicians and patients can consider alternative diabetes devices without isobornyl acrylate, she said.

In the future, close collaboration between clinicians and the medical device industry to develop appropriate labeling can help increase awareness of the potential for allergic reactions, she added.

Dr. Honari had no relevant financial conflicts to disclose.

WASHINGTON – The American Contact Dermatitis Society has selected isobornyl acrylate the contact allergen of the year. It is an acrylic monomer used as an adhesive.

Vidyard Video

Among other applications, isobornyl acrylate is often used in medical devices. The selection was made based in part on multiple case reports of diabetes patients developing contact allergies to their diabetes devices, such as insulin pumps, explained Golara Honari, MD, of Stanford (Calif.) University, who presented the selection at the ACDS annual meeting.

The significance of this allergen is that testing through routine panels does not identify it, so clinician awareness is especially important, Dr. Honari noted in a video interview at the meeting.

Most of the reported contact allergen cases have been in patients with diabetes, but clinicians should think about other possible sources, such as acrylic nails, she said. As for treatment, clinicians and patients can consider alternative diabetes devices without isobornyl acrylate, she said.

In the future, close collaboration between clinicians and the medical device industry to develop appropriate labeling can help increase awareness of the potential for allergic reactions, she added.

Dr. Honari had no relevant financial conflicts to disclose.

WASHINGTON – The American Contact Dermatitis Society has selected isobornyl acrylate the contact allergen of the year. It is an acrylic monomer used as an adhesive.

Vidyard Video

Among other applications, isobornyl acrylate is often used in medical devices. The selection was made based in part on multiple case reports of diabetes patients developing contact allergies to their diabetes devices, such as insulin pumps, explained Golara Honari, MD, of Stanford (Calif.) University, who presented the selection at the ACDS annual meeting.

The significance of this allergen is that testing through routine panels does not identify it, so clinician awareness is especially important, Dr. Honari noted in a video interview at the meeting.

Most of the reported contact allergen cases have been in patients with diabetes, but clinicians should think about other possible sources, such as acrylic nails, she said. As for treatment, clinicians and patients can consider alternative diabetes devices without isobornyl acrylate, she said.

In the future, close collaboration between clinicians and the medical device industry to develop appropriate labeling can help increase awareness of the potential for allergic reactions, she added.

Dr. Honari had no relevant financial conflicts to disclose.

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.^1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,^3,4 type 2 diabetes mellitus,^5,6 hypertension,⁵ dyslipidemia,^3,7 metabolic syndrome,⁷ atherosclerosis,⁸ peripheral vascular disease,⁹ coronary artery calcification,¹⁰ myocardial infarction,^11-13 stroke,^9,14 and cardiac death.^15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.^17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.

Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.

Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.¹⁹ Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,²⁰ and psoriasis patients also might consume less whole-grain fiber.²¹ Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,¹⁸ which also has been supported by response to anti-inflammatory medications such as mesalazine.²² Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al²³ found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.²⁴ Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al²⁵ hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (T_H17) pathway,²⁵ which also has been found to play a role in psoriasis pathogenesis.^26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.

We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al²⁸ found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.²⁹ Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.^30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.^1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,^3,4 type 2 diabetes mellitus,^5,6 hypertension,⁵ dyslipidemia,^3,7 metabolic syndrome,⁷ atherosclerosis,⁸ peripheral vascular disease,⁹ coronary artery calcification,¹⁰ myocardial infarction,^11-13 stroke,^9,14 and cardiac death.^15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.^17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.

Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.

Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.¹⁹ Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,²⁰ and psoriasis patients also might consume less whole-grain fiber.²¹ Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,¹⁸ which also has been supported by response to anti-inflammatory medications such as mesalazine.²² Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al²³ found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.²⁴ Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al²⁵ hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (T_H17) pathway,²⁵ which also has been found to play a role in psoriasis pathogenesis.^26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.

We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al²⁸ found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.²⁹ Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.^30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.

Psoriasis is a chronic skin condition affecting approximately 2% to 3% of the population.^1,2 Beyond cutaneous manifestations, psoriasis is a systemic inflammatory state that is associated with an increased risk for cardiovascular disease, including obesity,^3,4 type 2 diabetes mellitus,^5,6 hypertension,⁵ dyslipidemia,^3,7 metabolic syndrome,⁷ atherosclerosis,⁸ peripheral vascular disease,⁹ coronary artery calcification,¹⁰ myocardial infarction,^11-13 stroke,^9,14 and cardiac death.^15,16

Psoriasis also has been associated with inflammatory bowel disease (IBD), possibly because of similar autoimmune mechanisms in the pathogenesis of both diseases.^17,18 However, there is no literature regarding the risk for acute gastrointestinal pathologies such as appendicitis, cholecystitis, or diverticulitis in patients with psoriasis.

The primary objective of this study was to examine if patients with psoriasis are at increased risk for appendicitis, cholecystitis, or diverticulitis compared to the general population. The secondary objective was to determine if patients with severe psoriasis (ie, patients treated with phototherapy or systemic therapy) are at a higher risk for these conditions compared to patients with mild psoriasis.

Methods

Patients and Tools
A descriptive, population-based cohort study design with controls from a matched cohort was used to ascertain the effect of psoriasis status on patients’ risk for appendicitis, cholecystitis, or diverticulitis. Our cohort was selected using administrative data from Kaiser Permanente Southern California (KPSC) during the study period (January 1, 2004, through December 31, 2016).

Kaiser Permanente Southern California is a large integrated health maintenance organization that includes approximately 4 million patients as of December 31, 2016, and includes roughly 20% of the region’s population. The geographic area served extends from Bakersfield in the lower California Central Valley to San Diego on the border with Mexico. Membership demographics, socioeconomic status, and ethnicity composition are representative of California.

Patients were included if they had a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1; International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L40.0, L40.4, L40.8, or L40.9) for at least 3 visits between January 1, 2004, and December 31, 2016. Patients were not excluded if they also had a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0; ICD-10-CM code L40.5x). Patients also must have been continuously enrolled for at least 1 year before and 1 year after the index date, which was defined as the date of the third psoriasis diagnosis.

Each patient with psoriasis was assigned to 1 of 2 cohorts: (1) severe psoriasis: patients who received UVB phototherapy, psoralen plus UVA phototherapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, adalimumab, infliximab, ustekinumab, efalizumab, alefacept, secukinumab, or ixekizumab during the study period; and (2) mild psoriasis: patients who had a diagnosis of psoriasis who did not receive one of these therapies during the study period.

Patients were excluded if they had a history of appendicitis, cholecystitis, or diverticulitis at any time before the index date. Only patients older than 18 years were included.

Patients with psoriasis were frequency matched (1:5) with healthy patients, also from the KPSC network. Individuals were matched by age, sex, and ethnicity.

Statistical Analysis
Baseline characteristics were described with means and SD for continuous variables as well as percentages for categorical variables. Chi-square tests for categorical variables and the Mann-Whitney U Test for continuous variables were used to compare the patients’ characteristics by psoriasis status. Cox proportional hazards regression models were used to examine the risk for appendicitis, cholecystitis, or diverticulitis among patients with and without psoriasis and among patients with mild and severe psoriasis. Proportionality assumption was validated using Pearson product moment correlation between the scaled Schoenfeld residuals and log transformed time for each covariate.

Results were presented as crude (unadjusted) hazard ratios (HRs) and adjusted HRs, where confounding factors (ie, age, sex, ethnicity, body mass index [BMI], alcohol use, smoking status, income, education, and membership length) were adjusted. All tests were performed with SAS EG 5.1 and R software. P<.05 was considered statistically significant. Results are reported with the 95% confidence interval (CI), when appropriate.

Results

A total of 1,690,214 KPSC patients were eligible for the study; 10,307 (0.6%) met diagnostic and inclusion criteria for the psoriasis cohort. Patients with psoriasis had a significantly higher mean BMI (29.9 vs 28.7; P<.0001) as well as higher mean rates of alcohol use (56% vs 53%; P<.0001) and smoking (47% vs 38%; P<.01) compared to controls. Psoriasis patients had a shorter average duration of membership within the Kaiser network (P=.0001) compared to controls.

A total of 7416 patients met criteria for mild psoriasis and 2891 patients met criteria for severe psoriasis (eTable). Patients with severe psoriasis were significantly younger and had significantly higher mean BMI compared to patients with mild psoriasis (P<.0001 and P=.0001, respectively). No significant difference in rates of alcohol or tobacco use was detected among patients with mild and severe psoriasis.

Diverticulitis
Patients with psoriasis had a significantly greater prevalence of diverticulitis compared to the control cohort (5.1% vs 4.2%; P<.0001). There was no difference in prevalence between the severe psoriasis group and the mild psoriasis group (P=.96), but the time to diagnosis of diverticulitis was shorter in the severe psoriasis group than in the mild psoriasis group (7.2 years vs 7.9 years; P<.0001). Psoriasis patients had an incidence rate of diverticulitis of 6.61 per 1000 patient-years compared to 5.38 per 1000 patient-years in the control group. Psoriasis conferred a higher risk for diverticulitis in both the crude and adjusted models (HR, 1.23; 95% CI, 1.11-1.35 [P<.001] and HR, 1.16; 95% CI, 1.05-1.29; [P<.01], respectively)(Table 3); however, when stratified by disease severity, only patients with severe psoriasis were found to be at higher risk (HR, 1.26; 95% CI, 1.15-1.61; P<.001 for the adjusted model).

Comment

The objective of this study was to examine the background risks for specific gastrointestinal pathologies in a large cohort of patients with psoriasis compared to the general population. After adjusting for measured confounders, patients with severe psoriasis had a significantly higher risk of diverticulitis compared to the general population. Although more patients with severe psoriasis developed appendicitis or cholecystitis, the difference was not significant.

The pathogenesis of diverticulosis and diverticulitis has been thought to be related to increased intracolonic pressure and decreased dietary fiber intake, leading to formation of diverticula in the colon.¹⁹ Our study did not correct for differences in diet between the 2 groups, making it a possible confounding variable. Studies evaluating dietary habits of psoriatic patients have found that adult males with psoriasis might consume less fiber compared to healthy patients,²⁰ and psoriasis patients also might consume less whole-grain fiber.²¹ Furthermore, fiber deficiency also might affect gut flora, causing low-grade chronic inflammation,¹⁸ which also has been supported by response to anti-inflammatory medications such as mesalazine.²² Given the autoimmune association between psoriasis and IBD, it is possible that psoriasis also might create an environment of chronic inflammation in the gut, predisposing patients with psoriasis to diverticulitis. However, further research is needed to better evaluate this possibility.

Our study also does not address any potential effects on outcomes of specific treatments for psoriasis. Brandl et al²³ found that patients on immunosuppressive therapy for autoimmune diseases had longer hospital and intensive care unit stays, higher rates of emergency operations, and higher mortality while hospitalized. Because our results suggest that patients with severe psoriasis, who are therefore more likely to require treatment with an immunomodulator, are at higher risk for diverticulitis, these patients also might be at risk for poorer outcomes.

There is no literature evaluating the relationship between psoriasis and appendicitis. Our study found a slightly lower incidence rate compared to the national trend (9.38 per 10,000 patient-years in the United States in 2008) in both healthy patients and psoriasis patients.²⁴ Of note, this statistic includes children, whereas our study did not, which might in part account for the lower rate. However, Cheluvappa et al²⁵ hypothesized a relationship between appendicitis and subsequent appendectomy at a young age and protection against IBD. They also found that the mechanism for protection involves downregulation of the helper T cell (T_H17) pathway,²⁵ which also has been found to play a role in psoriasis pathogenesis.^26,27 Although our results suggest that the risk for appendicitis is not increased for patients with psoriasis, further research might be able to determine if appendicitis and subsequent appendectomy also can offer protection against development of psoriasis.

We found that patients with severe psoriasis had a higher incidence rate of cholecystitis compared to patients with mild psoriasis. Egeberg et al²⁸ found an increased risk for cholelithiasis among patients with psoriasis, which may contribute to a higher rate of cholecystitis. Although both acute and chronic cholecystitis were incorporated in this study, a Russian study found that chronic cholecystitis may be a predictor of progression of psoriasis.²⁹ Moreover, patients with severe psoriasis had a shorter duration to diagnosis of cholecystitis than patients with mild psoriasis. It is possible that patients with severe psoriasis are in a state of greater chronic inflammation than those with mild psoriasis, and therefore, when combined with other risk factors for cholecystitis, may progress to disease more quickly. Alternatively, this finding could be treatment related, as there have been reported cases of cholecystitis related to etanercept use in patients treated for psoriasis and juvenile polyarticular rheumatoid arthritis.^30,31 The relationship is not yet well defined, however, and further research is necessary to evaluate this association.

Study Strengths
Key strengths of this study include the large sample size and diversity of the patient population. Kaiser Permanente Southern California membership generally is representative of the broader community, making our results fairly generalizable to populations with health insurance. Use of a matched control cohort allows the results to be more specific to the disease of interest, and the population-based design minimizes bias.

Study Limitations
This study has several limitations. Although the cohorts were categorized based on type of treatment received, exact therapies were not specified. As a retrospective study, it is difficult to control for potential confounding variables that are not included in the electronic medical record. The results of this study also demonstrated significantly shorter durations to diagnosis of all 3 conditions, indicating that surveillance bias may be present.

Conclusion

Patients with psoriasis may be at an increased risk for diverticulitis compared to patients without psoriasis, which could be due to the chronic inflammatory state induced by psoriasis. Therefore, it may be beneficial for clinicians to evaluate psoriasis patients for other risk factors for diverticulitis and subsequently provide counseling to these patients to minimize their risk for diverticulitis. Psoriasis patients do not appear to be at an increased risk for appendicitis or cholecystitis compared to controls; however, further research is needed for confirmation.