Comorbid Psoriasis and Metabolic Syndrome: Clinical Implications and Optimal Management

Figures & data

Table 1 Potential Side Effects of Anti-Psoriatic Drugs on Cardiovascular Risk Factors

Drug	Toxicity/Benefit^Citation16
Acitretin	Coronary heart disease, dyslipidemia
Corticosteroids	Dyslipidemia, hyperglycemia, hypertension
Cyclosporine	Hypertension, hypercholesterolemia, dyslipidemia
Methotrexate	Decreases vascular risk

Notes: Adapted from Kakarala CL, Hassan M, Belavadi R, et al. Beyond the skin plaques: psoriasis and its cardiovascular comorbidities. Cureus. 2021;13(11):e19679. Copyright© 2021, Kakarala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.¹⁶

Table 2 Risk Factors for Developing Type 2 Diabetes in Children (Left Panel) and Adults (Right Panel)

Risk Factors for Type 2 Diabetes in Children^Citation33	Risk Factors for Type 2 Diabetes in Adults^Citation22
Body mass index ≥ 85th percentile	Body mass index ≥ 25 AND
Family history of type 2 diabetes in a first-degree or second-degree relative	Family history of type 2 diabetes in a first-degree relative
Native American, African American, Latino, Asian American, Pacific Islander race/ethnicity	Native American, African American, Latino, Asian American, Pacific Islander race/ethnicity
	Physical inactivity
Conditions associated with insulin resistance: polycystic ovary syndrome, acanthosis nigricans, hypertension, dyslipidemia, small-for-gestational-age birth weight	Conditions associated with insulin resistance: polycystic ovary syndrome, acanthosis nigricans, hypertension, dyslipidemia, small-for-gestational-age birth weight
Maternal history of diabetes or gestational diabetes during the child’s gestation	Maternal history of diabetes or gestational diabetes during the child’s gestation
	Severe obesity, hypertension, dyslipidemia, history of CVD

Notes: Reproduced from Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness andattention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073–1113. Copyright 2019, with permission from Elsevier.²² Data from Osier et al.³³

Abbreviation: CVD, cardiovascular disease.

Table 3 Comparison of Inflammatory and Degenerative Pain Pattern

Inflammatory Arthritis	Degenerative/Osteoarthritis
Stiffness after a period of inactivity (30–60 min)	No significant period of stiffness after inactivity
Redness, warmth, swelling	Worsens with activity, end of the day
Subacute-chronic duration	Specific joint patterns (base of thumb)
Systemic symptoms (fatigue, uveitis etc.)
Response to anti-inflammatory treatment
Family history

Table 4 Risk Factors NAFLD⁵⁶

Obesity

Type 2 diabetes, Insulin resistance

Dyslipidemia

Hypertension

Hypopituitarism

Note: Data from Powell et al.⁵⁶

Table 5 Comorbidity Screening Tool for Adult Psoriasis Patients

Comorbidity	Recommendations from the Literature	Practical Recommendation
Cardiovascular disease including hypertension	Screen psoriasis patients with a family history of cardiovascular events^Citation63 Screening intervals may vary between patients on the basis of their individual risk factors and overall health^Citation22 Current evidence does not support restrictions on antihypertensive medications in patients with psoriasis^Citation31	Measure blood pressure every visit Educate patient on the reason why you follow up on blood pressure
Dyslipidemia	Moderate to severe psoriasis patients are recommended to undergo periodic screening with lipid tests (eg fasting total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides)^Citation31	Screen for blood lipids (Cholesterol, Triglycerides) 1/year, no fasting required^Citation64 Consider more frequent testing in uncontrolled psoriasis patients Consider fasting blood test when history of disturbed blood lipids
Obesity	BMI and waist circumference annually with moderate to severe psoriasis^Citation31 To encourage the measurement of blood pressure, waist, circumference, fasting blood glucose, hemoglobin A1C, and fasting lipid levels with their GP when indicated	Check weight/BMI every visit Encourage physical activities
Type 2 diabetes	BSA greater than 10%, should be targeted for diabetes prevention^Citation65 Regular monitoring of fasting blood glucose and/or hemoglobin A1C levels in patients with moderate to severe psoriasis is recommended^Citation31	Screen for fasting glycemia and/or HbA1C 1/year Consider more frequent testing in uncontrolled psoriasis patients
Metabolic syndrome	Inform about risk and encourage to go to GP for the measurement of blood pressure, waist circumference, fasting blood glucose, hemoglobin A1C, and fasting lipid levels when indicated^Citation31 BMI and waist circumference annually in patients with moderate to severe psoriasis^Citation31	Educate psoriasis patients about the increased risk of MetS, its association with cardiovascular disease and preventive measurements.
Psoriatic arthritis	Inflammation, RX, clinical examination and questionnaires^Citation22 Each visit asking for joint pain, stiffness and swelling^Citation31 Asses smoking (-cessation) status and BMI^Citation66	Assess joint involvement during every visit Educate patients about associated rheumatological disease
Nonalcoholic fatty liver disease (NAFLD)	Abdominal ultrasonography, BMI, AST, ALT, glucose, lipids, blood pressure, low platelets. NAFLD fibrosis score (age, BMI, IFG and Diabetes, AST-to-ALT ratio, platelets and albumin) or FIB-4 score (age, AST, ALT and platelet)^Citation56 They are simple to use and low scores have a good negative prediction for liver fibrosis retesting 3–5 years after initial assessment has been proposed	Multi-disciplinary approach with hepatologist
IBD	Patients should be informed of this relationship by their dermatologist; attention should be paid to signs and symptoms of bowel disease that would warrant further evaluation by the patient’s primary care provider or gastroenterologist^Citation22	Educate psoriasis patients about the increased risk of IBD Determine fecal calprotectin when Crohn’s disease is suspected

Abbreviations: BMI, body mass index; GP, general practitioner; MetS, metabolic syndrome; IFG, impaired fasting glycemia; ALT, alanine-amino-transferase; AST, aspartate-amino-transferase; IBD, inflammatory bowel disease.

Table 6 Comorbidity Screening Tool for Children and Adolescents with Psoriasis

Comorbidity	Recommendations from the Literature	Practical Recommendation
Cardiovascular disease including hypertension	Starting at 3 years of age, using age, sex, and height reference charts^Citation33 Starting at 3 years, yearly by their primary care provider^Citation37	Measure blood pressure every visit Report high blood pressure to GP Encourage physical activities and weight reduction in first line
Dyslipidemia	Universal lipid screening should be performed during the following 2 age ranges: 9 to 11 years old and 17 to 21 years old^Citation33 Only screening if additional risk factor Family history of cardiovascular disease, hypertension, smoking, obesity, HDL <40 mg/dL, Type 1 or 2 diabetes mellitus, renal disease, nephrotic syndrome, postorthotopic heart transplant, Kawasaki disease with current or regressed aneurysms, HIV, chronic inflammatory disease)^Citation33	Consider testing in uncontrolled psoriasis patients Screen prior to initiation of (and during treatment with) blood lipid altering medication
Obesity	BMI as of the age of 2, yearly^Citation33	Check weight/BMI every visit Encourage physical activities
Type 2 Diabetes	Fasting serum glucose from 10 years/year of onset puberty every 3 years if patient has obesity^Citation33	Consider testing in uncontrolled psoriasis patients
Metabolic syndrome	Assessment among children and adolescents has not been as clear Central obesity, high blood pressure (Systolic or diastolic BP ≥ 90% for age, sex, height, TG ≥ 110 mg/dL, HDL ≤ 40 mg/dL, Glucose≥100 mg/dL or known T2DM^Citation41	See recommendations for dyslipidemia, obesity, type 2 diabetes
Psoriatic arthritis	Medical history and physical examination,^Citation33 every check up	Assess joint involvement during every visit Educate psoriasis patients and parents about associated rheumatological disease
Nonalcoholic fatty liver disease (NAFLD)	All children who are overweight with additional risk factors (central adiposity, insulin resistance prediabetes or diabetes, dyslipidemia, obstructive sleep apnea or family history of NAFLD/NASH) should be screened with ALT measurement starting at 9 to 11 years of age.^Citation33	To our knowledge, there is currently no evidence supporting screening of patients with psoriasis with normal BMI
IBD	For patients who have decreased growth rate, unexplained weight loss, or symptoms consistent with inflammatory bowel disease (nausea, vomiting, abdominal pain, chronic diarrhea), formal gastrointestinal evaluation should be considered.^Citation33	Educate psoriasis patients about the increased risk of IBD

Abbreviations: BMI, body mass index; GP, general practitioner; AST, alanine-amino-transferase; IBD, inflammatory bowel disease; HDL, high-density lipoprotein; NASH, nonalcoholic steatohepatitis; BP, blood pressure.

Table 7 Treatment Recommendations for Comorbidities in Adult Psoriasis Patients

Comorbidity	Recommendations from the Literature	Practical Recommendation UZ Leuven
Cardiovascular disease including hypertension	Educate patients about the risk^Citation31 Physicians should be aware of the potential for cyclosporine to induce hypertension, which should be treated, specifically with amlodipine^Citation31 TNF-inh are contra-indicated with patients with New York Heart Association Class III or Class IV congestive heart failure^Citation22 ACE-I or ARB +- CCB/thiazide diuretics^Citation67	Report high blood pressure to GP Refer to GP for initiation of antihypertensive therapy Encourage physical activities and weight reduction
Dyslipidemia	Patients with elevated fasting triglycerides or LDL, cholesterol should be referred to their PCP for further management^Citation31	Encourage physical activities Refer to nutritionist for education and support
Obesity	Stimulate weight loss^Citation31 Target waist circumference: 94cm for males; 80cm for females.^Citation68 Low energy diet (LED)^Citation69	Aim for realistic weight reduction: - 0.5–1 kg/month Encourage physical activities Refer to nutritionist for education and support
Type 2 Diabetes	Patients who meet criteria for prediabetes or diabetes should be referred to their GP for further assessment and management	Refer to GP for initiation of treatment
Metabolic syndrome	See recommendations for dyslipidemia, obesity, type 2 diabetes	See recommendations for dyslipidemia, obesity, type 2 diabetes
Psoriatic arthritis	Imaging and laboratory tests to evaluate for signs of systemic inflammation (erythrocyte sedimentation rate, C-reactive protein). Full rheumatologic consultation is warranted in challenging cases.^Citation31 Ideally, dermatologists initiate treatment with a medication that is effective for both psoriasis and PsA^Citation70	Refer to rheumatologist for rheumatological evaluation and treatment Consider systemic treatment effective for both cutaneous and articular psoriatic disease (eg methotrexate, biologics) Consider avoiding treatments not effective for articular disease (eg cyclosporine and/or acitretin)
Nonalcoholic fatty liver disease (NAFLD)	Weight loss of more than 5–7% reduces hepatic fat content and steatohepatitis, and, for weight loss in excess of 10%, even fibrosis is reduced in a large proportion of people^Citation56 A BMI > 30 kg/m2 increases the risk of NAFLD 9–fold compared to a BMI of 22^Citation71	Weight reduction: −0.5kg/month Refer to nutritionist
IBD	Interleukin 17 inhibitor therapy should be avoided in patients with IBD.^Citation22 Referral GE and GP if complaints^Citation22	Refer to GE

Abbreviations: ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockers; CCB, calcium channel blockers; BMI, body mass index; GP, general practitioner; MetS, metabolic syndrome; AST, alanine-amino-transferase; AST, aspartate-amino-transferase; IBD, inflammatory bowel disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BP, blood pressure; GE, gastroenterologist; PsA, psoriatic arthritis.

Table 8 Treatment Recommendations for Comorbidities in Children and Adolescents with Psoriasis

Comorbidity	Recommendations from the Literature	Practical Recommendation
Cardiovascular disease including hypertension	Education, specialist referral^Citation37	Report high blood pressure to GP/pediatrician Refer to GP/pediatrician for follow-up and/or treatment Encourage physical activities and weight reduction if in place
Dyslipidemia	Education on dyslipidemia, referral to their GP or an endocrinologist for further assessment and management.^Citation37	Encourage physical activities Refer to nutritionist for education and support Refer to GP/pediatrician for follow-up and/or treatment
Obesity	Nutritional counseling, referral pediatric tertiary weight management center is particularly important for those children with a BMI greater than 120% of the 95th percentile.^Citation33	Aim for realistic weight reduction: - 0.5–1 kg/month Encourage physical activities Refer to nutritionist for education and support
Type 2 Diabetes	Pediatric psoriasis patients with insulin resistance or diabetes mellitus should be referred to their primary care provider or an endocrinologist for further assessment and management.^Citation37	Refer to GP/pediatrician for initiation of treatment
MetS	Pediatric patients with psoriasis who have been identified as having cardiovascular risk factors such as obesity, dyslipidemia, diabetes, hypertension, or metabolic syndrome should be referred to appropriate specialists for further evaluation and management^Citation37	See recommendations for dyslipidemia, obesity, type 2 diabetes
Psoriatic arthritis	Pediatric patients with psoriasis who show signs and symptoms of inflammatory arthritis should be referred to a rheumatologist with pediatric expertise, if available, for further evaluation and management.^Citation37	Refer to rheumatologist for rheumatological evaluation and treatment Consider systemic treatment effective for both cutaneous and articular psoriatic disease (eg methotrexate, biologics) Consider avoiding treatments not effective for articular disease (eg cyclosporine and/or acitretin)
Nonalcoholic fatty liver disease (NAFLD)	Weight loss^Citation72 No medication or supplement is recommended for routine treatment of NAFLD^Citation72	Weight reduction: −0.5kg/month Refer to nutritionist
IBD	Pediatric patients with psoriasis who show signs and symptoms of inflammatory bowel disease should be considered for consultation with a gastroenterologist with pediatric expertise, if available, for further evaluation and management.^Citation37	Refer to GE

Abbreviations: GP, general practitioner; BMI, body mass index; GE, gastroenterologist.

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