Cutis

The Diagnosis: Paraneoplastic Acanthosis Nigricans 

Histopathologic examination demonstrated verrucous epidermal hyperplasia (Figure, A). Fungal organisms were identified with an Alcian blue and periodic acid-Schiff stain (Figure, B). The organisms demonstrated a vertical orientation in relation to the mucosal surface, which was consistent with candidal organisms.  

Given the rapid eruption of these plaques, the distribution on the oral and palmar surfaces (tripe palms), and the minimal improvement with both systemic steroids and antifungal treatment, a diagnosis of paraneoplastic acanthosis nigricans with secondary candidal infection was made. Drug-induced cheilitis was considered; however, improvement with discontinuation of the suspected offending drug would have been expected. Although chronic mucocutaneous candidiasis was possible, more prompt improvement upon initiation of systemic antifungal therapy would have been observed. Oral Crohn disease should be included in the differential, but it was unlikely given the lack of granulomas on pathology and absence of history of gastrointestinal tract symptoms. Melkersson-Rosenthal syndrome also was unlikely given the lack of facial nerve palsy as well as the lack of granulomas on pathology. Furthermore, none of these options would be associated with tripe palms, as seen in our patient.  

Acanthosis nigricans is a localized skin disorder characterized by hyperpigmented velvety plaques arising in flexural and intertriginous regions. Although most cases (80%) are associated with idiopathic or benign conditions, the link between acanthosis nigricans and an underlying malignancy has been well documented.^1-3 Most commonly associated with an underlying intra-abdominal malignancy (often gastric carcinoma), the lesions of paraneoplastic acanthosis nigricans are indistinguishable from their benign counterparts^.1,4 When the condition presents abruptly and extensively in a nonobese patient, prompt workup for malignancy should be initiated. Rapid onset and atypical distribution (ie, palmar, perioral, or mucosal) more commonly is associated with a paraneoplastic etiology.^5,6 

Histopathology for acanthosis nigricans shows hyperkeratosis and epidermal papillomatosis. Horn pseudocyst formation is possible, but usually no hyperpigmentation is observed. The findings typically are indistinguishable from seborrheic keratoses, epidermal nevi, or lesions of confluent and reticulated papillomatosis of Gougerot and Carteaud.² 

The underlying pathogenesis of acanthosis nigricans is poorly understood. In the benign subtype, insulin resistance commonly has been described. In the paraneoplastic subtype, it is proposed that the tumor produces a transforming growth factor that mimics epidermal growth factor and leads to keratinocyte proliferation.^7,8 Paraneoplastic acanthosis nigricans has the potential to arise at any point of tumor development, further contributing to the diagnostic challenge. Treatment of the skin lesions involves management of the underlying malignancy. Unfortunately, many such malignancies often are at an advanced stage, and subsequent prognosis is poor.² 

The Diagnosis: Paraneoplastic Acanthosis Nigricans 

Histopathologic examination demonstrated verrucous epidermal hyperplasia (Figure, A). Fungal organisms were identified with an Alcian blue and periodic acid-Schiff stain (Figure, B). The organisms demonstrated a vertical orientation in relation to the mucosal surface, which was consistent with candidal organisms.  

Given the rapid eruption of these plaques, the distribution on the oral and palmar surfaces (tripe palms), and the minimal improvement with both systemic steroids and antifungal treatment, a diagnosis of paraneoplastic acanthosis nigricans with secondary candidal infection was made. Drug-induced cheilitis was considered; however, improvement with discontinuation of the suspected offending drug would have been expected. Although chronic mucocutaneous candidiasis was possible, more prompt improvement upon initiation of systemic antifungal therapy would have been observed. Oral Crohn disease should be included in the differential, but it was unlikely given the lack of granulomas on pathology and absence of history of gastrointestinal tract symptoms. Melkersson-Rosenthal syndrome also was unlikely given the lack of facial nerve palsy as well as the lack of granulomas on pathology. Furthermore, none of these options would be associated with tripe palms, as seen in our patient.  

Acanthosis nigricans is a localized skin disorder characterized by hyperpigmented velvety plaques arising in flexural and intertriginous regions. Although most cases (80%) are associated with idiopathic or benign conditions, the link between acanthosis nigricans and an underlying malignancy has been well documented.^1-3 Most commonly associated with an underlying intra-abdominal malignancy (often gastric carcinoma), the lesions of paraneoplastic acanthosis nigricans are indistinguishable from their benign counterparts^.1,4 When the condition presents abruptly and extensively in a nonobese patient, prompt workup for malignancy should be initiated. Rapid onset and atypical distribution (ie, palmar, perioral, or mucosal) more commonly is associated with a paraneoplastic etiology.^5,6 

Histopathology for acanthosis nigricans shows hyperkeratosis and epidermal papillomatosis. Horn pseudocyst formation is possible, but usually no hyperpigmentation is observed. The findings typically are indistinguishable from seborrheic keratoses, epidermal nevi, or lesions of confluent and reticulated papillomatosis of Gougerot and Carteaud.² 

The underlying pathogenesis of acanthosis nigricans is poorly understood. In the benign subtype, insulin resistance commonly has been described. In the paraneoplastic subtype, it is proposed that the tumor produces a transforming growth factor that mimics epidermal growth factor and leads to keratinocyte proliferation.^7,8 Paraneoplastic acanthosis nigricans has the potential to arise at any point of tumor development, further contributing to the diagnostic challenge. Treatment of the skin lesions involves management of the underlying malignancy. Unfortunately, many such malignancies often are at an advanced stage, and subsequent prognosis is poor.² 

The Diagnosis: Paraneoplastic Acanthosis Nigricans 

Histopathologic examination demonstrated verrucous epidermal hyperplasia (Figure, A). Fungal organisms were identified with an Alcian blue and periodic acid-Schiff stain (Figure, B). The organisms demonstrated a vertical orientation in relation to the mucosal surface, which was consistent with candidal organisms.  

Given the rapid eruption of these plaques, the distribution on the oral and palmar surfaces (tripe palms), and the minimal improvement with both systemic steroids and antifungal treatment, a diagnosis of paraneoplastic acanthosis nigricans with secondary candidal infection was made. Drug-induced cheilitis was considered; however, improvement with discontinuation of the suspected offending drug would have been expected. Although chronic mucocutaneous candidiasis was possible, more prompt improvement upon initiation of systemic antifungal therapy would have been observed. Oral Crohn disease should be included in the differential, but it was unlikely given the lack of granulomas on pathology and absence of history of gastrointestinal tract symptoms. Melkersson-Rosenthal syndrome also was unlikely given the lack of facial nerve palsy as well as the lack of granulomas on pathology. Furthermore, none of these options would be associated with tripe palms, as seen in our patient.  

Acanthosis nigricans is a localized skin disorder characterized by hyperpigmented velvety plaques arising in flexural and intertriginous regions. Although most cases (80%) are associated with idiopathic or benign conditions, the link between acanthosis nigricans and an underlying malignancy has been well documented.^1-3 Most commonly associated with an underlying intra-abdominal malignancy (often gastric carcinoma), the lesions of paraneoplastic acanthosis nigricans are indistinguishable from their benign counterparts^.1,4 When the condition presents abruptly and extensively in a nonobese patient, prompt workup for malignancy should be initiated. Rapid onset and atypical distribution (ie, palmar, perioral, or mucosal) more commonly is associated with a paraneoplastic etiology.^5,6 

Histopathology for acanthosis nigricans shows hyperkeratosis and epidermal papillomatosis. Horn pseudocyst formation is possible, but usually no hyperpigmentation is observed. The findings typically are indistinguishable from seborrheic keratoses, epidermal nevi, or lesions of confluent and reticulated papillomatosis of Gougerot and Carteaud.² 

The underlying pathogenesis of acanthosis nigricans is poorly understood. In the benign subtype, insulin resistance commonly has been described. In the paraneoplastic subtype, it is proposed that the tumor produces a transforming growth factor that mimics epidermal growth factor and leads to keratinocyte proliferation.^7,8 Paraneoplastic acanthosis nigricans has the potential to arise at any point of tumor development, further contributing to the diagnostic challenge. Treatment of the skin lesions involves management of the underlying malignancy. Unfortunately, many such malignancies often are at an advanced stage, and subsequent prognosis is poor.² 

Within the last decade, almost 3000 articles have been published on the role of diet in the prevention and management of dermatologic conditions. Patients are increasingly interested in—and employing—dietary modifications that may influence skin appearance and aid in the treatment of cutaneous disease.¹ It is essential that dermatologists are familiar with existing evidence on the role of diet in dermatology to counsel patients appropriately. Herein, we discuss the compositions of several popular diets and their proposed utility for dermatologic purposes. We highlight the limited literature that exists surrounding this topic and emphasize the need for future, well-designed clinical trials that study the impact of diet on skin disease.

Ketogenic Diet

The ketogenic diet has a macronutrient profile composed of high fat, low to moderate protein, and very low carbohydrates. Nutritional ketosis occurs as the body begins to use free fatty acids (via beta oxidation) as the primary metabolite driving cellular metabolism. It has been suggested that the ketogenic diet may impart beneficial effects on skin disease; however, limited literature exists on the role of nutritional ketosis in the treatment of dermatologic conditions.

Mechanistically, the ketogenic diet decreases the secretion of insulin and insulinlike growth factor 1, resulting in a reduction of circulating androgens and increased activity of the retinoid X receptor.² In acne vulgaris, it has been suggested that the ketogenic diet may be beneficial in decreasing androgen-induced sebum production and the overproliferation of keratinocytes.^2-7 The ketogenic diet is one of the most rapidly effective dietary strategies for normalizing both insulin and androgens, thus it may theoretically be useful for other metabolic and hormone-dependent skin diseases, such as hidradenitis suppurativa.^8,9

The cutaneous manifestations associated with chronic hyperinsulinemia and hyperglycemia are numerous and include acanthosis nigricans, acrochordons, diabetic dermopathy, scleredema diabeticorum, bullosis diabeticorum, keratosis pilaris, and generalized granuloma annulare. There also is an increased risk for bacterial and fungal skin infections associated with hyperglycemic states.¹⁰ The ketogenic diet is an effective nonpharmacologic tool for normalizing serum insulin and glucose levels in most patients and may have utility in the aforementioned conditions.^11,12 In addition to improving insulin sensitivity, it has been used as a dietary strategy for weight loss.^11-15 Because obesity and metabolic syndrome are highly correlated with common skin conditions such as psoriasis, hidradenitis suppurativa, and androgenetic alopecia, there may be a role for employing the ketogenic diet in these patient populations.^16,17

Although robust clinical studies on ketogenic diets in skin disease are lacking, a recent single-arm, open-label clinical trial observed benefit in all 37 drug-naïve, overweight patients with chronic plaque psoriasis who underwent a ketogenic weight loss protocol. Significant reductions in psoriasis area and severity index (PASI) score and dermatology life quality index score were reported (P<.001).¹⁸ Another study of 30 patients with psoriasis found that a 4-week, low-calorie, ketogenic diet resulted in 50% improvement of PASI scores, 10% weight loss, and a reduction in the proinflammatory cytokines IL-1β and IL-2.¹⁹ Despite these results, it is a challenge to tease out if the specific dietary intervention or its associated weight loss was the main driver in these reported improvements in skin disease.

There is mixed evidence on the anti-inflammatory nature of the ketogenic diet, likely due to wide variation in the composition of foods included in individual diets. In many instances, the ketogenic diet is thought to possess considerable antioxidant and anti-inflammatory capabilities. Ketones are known activators of the nuclear factor erythroid 2–related factor 2 pathway, which upregulates the production of glutathione, a major endogenous intracellular antioxidant.²⁰ Additionally, dietary compounds from foods that are encouraged while on the ketogenic diet, such as sulforaphane from broccoli, also are independent activators of nuclear factor erythroid 2–related factor 2.²¹ Ketones are efficiently utilized by mitochondria, which also may result in the decreased production of reactive oxygen species and lower oxidative stress.²² Moreover, the ketone body β-hydroxybutyrate has demonstrated the ability to reduce proinflammatory IL-1β levels via suppression of nucleotide-binding domain-like receptor protein 3 inflammasome activity.^23,24 The activity of IL-1β is known to be elevated in many dermatologic conditions, including juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, hidradenitis suppurativa, Behçet disease, and other autoinflammatory syndromes.²⁵ Ketones also have been shown to inhibit the nuclear factor–κB proinflammatory signaling pathway.^22,26,27 Overexpression of IL-1β and aberrant activation of nuclear factor–κB are implicated in a variety of inflammatory, autoimmune, and oncologic cutaneous pathologies. The ketogenic diet may prove to be an effective adjunctive treatment for dermatologists to consider in select patient populations.^23,24,28-30

For patients with keratinocyte carcinomas, the ketogenic diet may offer the aforementioned anti-inflammatory and antioxidant effects, as well as suppression of the mechanistic target of rapamycin, a major regulator of cell metabolism and proliferation.^31,32 Inhibition of mechanistic target of rapamycin activity has been shown to slow tumor growth and reduce the development of squamous cell carcinoma.^25,33,34 The ketogenic diet also may exploit the preferential utilization of glucose exhibited by many types of cancer cells, thereby “starving” the tumor of its primary fuel source.^35,36 In vitro and animal studies in a variety of cancer types have demonstrated that a ketogenic metabolic state—achieved through the ketogenic diet or fasting—can sensitize tumor cells to chemotherapy and radiation while conferring a protective effect to normal cells.^37-40 This recently described phenomenon is known as differential stress resistance, but it has not been studied in keratinocyte malignancies or melanoma to date. Importantly, some basal cell carcinomas and BRAF V600E–mutated melanomas have worsened while on the ketogenic diet, suggesting more data is needed before it can be recommended for all cancer patients.^41,42 Furthermore, other skin conditions such as prurigo pigmentosa have been associated with initiation of the ketogenic diet.⁴³

Low FODMAP Diet

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that are poorly absorbed, osmotically active, and rapidly fermented by intestinal bacteria.⁴⁴ The low FODMAP diet has been shown to be efficacious for treatment of irritable bowel syndrome, small intestinal bacterial overgrowth (SIBO), and some cases of inflammatory bowel disease (IBD).^44-49 A low FODMAP diet may have potential implications for several dermatologic conditions.

Rosacea has been associated with various gastrointestinal tract disorders including irritable bowel syndrome, SIBO, and IBD.^50-54 A single study found that patients with rosacea had a 13-fold increased risk for SIBO.^55,56 Treatment of 40 patients with SIBO using rifaximin resulted in complete resolution of rosacea in all patients, with no relapse after a 3-year follow-up period.⁵⁵ Psoriasis also has been associated with SIBO and IBD.^57,58 One small study found that eradication of SIBO in psoriatic patients resulted in improved PASI scores and colorimetric values.⁵⁹

Although the long-term health consequences of the low FODMAP diet are unknown, further research on such dietary interventions for inflammatory skin conditions is warranted given the mounting evidence of a gut-skin connection and the role of the intestinal microbiome in skin health.^50,51

Gluten-Free Diet

Gluten is a protein found in a variety of grains. Although the role of gluten in the pathogenesis of celiac disease and dermatitis herpetiformis is indisputable, the deleterious effects of gluten outside of the context of these diseases remain controversial. There may be a compelling case for eliminating gluten in psoriasis patients with seropositivity for celiac disease. A recent systematic review found a 2.2-fold increased risk for celiac disease in psoriasis patients.⁶⁰ Antigliadin antibody titers also were found to be positively correlated with psoriatic disease severity.⁶¹ In addition, one open-label study found a reduction in PASI scores in 73% of patients with antigliadin antibodies after 3 months on a gluten-free diet compared to those without antibodies; however, the study only included 22 patients.⁶² Several other small studies have yielded similar results^63,64; however, antigliadin antibodies are neither the most sensitive nor specific markers of celiac disease, and additional testing should be completed in any patient who may carry this diagnosis. A survey study by the National Psoriasis Foundation found that the dietary change associated with the greatest skin improvement was removal of gluten and nightshade vegetables in approximately 50% of the 1200 psoriasis patients that responded.⁶⁵ Case reports of various dermatologic conditions including sarcoidosis, vitiligo, alopecia areata, lichen planus, dermatomyositis, pyoderma gangrenosum, erythema nodosum, leukocytoclastic vasculitis, linear IgA bullous dermatosis, and aphthous ulcerations have reportedly improved with a gluten-free diet; however, this should not be used as primary therapy in patients without celiac disease.^66-71 Because gluten-free diets can be expensive and challenging to follow, a formal assessment for celiac disease should be considered before recommendation of this dietary intervention.

Low Histamine Diet

Histamine is a biogenic amine produced by the decarboxylation of the amino acid histidine.⁷² It is found in several foods in varying amounts. Because bacteria can convert histidine into histamine, many fermented and aged foods such as kimchi, sauerkraut, cheese, and red wine contain high levels of histamine. Individuals who have decreased activity of diamine oxidase (DAO), an enzyme that degrades histamine, may be more susceptible to histamine intolerance.⁷² The symptoms of histamine intolerance are numerous and include gastrointestinal tract distress, rhinorrhea and nasal congestion, headache, urticaria, flushing, and pruritus. Histamine intolerance can mimic an IgE-mediated food allergy; however, allergy testing is negative in these patients. Unfortunately, there is no laboratory test for histamine intolerance; a double-blind, placebo-controlled food challenge is considered the gold-standard test.⁷²

As it pertains to dermatology, a low histamine diet may play a role in the treatment of certain patients with atopic dermatitis and chronic spontaneous urticaria. One study reported that 17 of 54 (31.5%) atopic patients had higher basal levels of serum histamine compared to controls.⁷³ Another study found that a histamine-free diet led to improvement in both histamine intolerance symptoms and atopic dermatitis disease severity (SCORing atopic dermatitis) in patients with low DAO activity.⁷⁴ In chronic spontaneous urticaria, a recent systematic review found that in 223 patients placed on a low histamine diet for 3 to 4 weeks, 12% and 44% achieved complete and partial remission, respectively.⁷⁵ Although treatment response based on a patient’s DAO activity level has not been correlated, a diet low in histamine may prove useful for patients with persistent atopic dermatitis and chronic spontaneous urticaria who have negative food allergy tests and report exacerbation of symptoms after ingestion of histamine-rich foods.^76,77

Mediterranean Diet

The Mediterranean diet has been touted as one of the healthiest diets to date, and large randomized clinical trials have demonstrated its effectiveness in weight loss, improving insulin sensitivity, and reducing inflammatory cytokine profiles.^78,79 A major criticism of the Mediterranean diet is that it has considerable ambiguity and lacks a precise definition due to the variability of what is consumed in different Mediterranean regions. Generally, the diet emphasizes high consumption of colorful fruits and vegetables, aromatic herbs and spices, olive oil, nuts, and seafood, as well as modest amounts of dairy, eggs, and red meat.⁸⁰ The anti-inflammatory effects of this diet largely have been attributed to its abundance of polyphenols, carotenoids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids (PUFAs).^80,81 Examples of polyphenols include resveratrol in red grapes, quercetin in apples and red onions, and curcumin in turmeric, while examples of carotenoids include lycopene in tomatoes and zeaxanthin in dark leafy greens. Oleic acid is a monounsaturated fatty acid present in high concentrations in olive oil, while eicosapentaenoic acid and docosahexaenoic acid are omega-3 PUFAs predominantly found in fish.⁸²

Unfortunately, rigorous clinical trials regarding the Mediterranean diet as it pertains to dermatology have not been undertaken. Numerous observational studies in patients with psoriasis have suggested that close adherence to the Mediterranean diet was associated with improvement in PASI scores.^83-86 The National Psoriasis Foundation now recommends a trial of the Mediterranean diet in some patients with psoriasis, emphasizing increased dietary intake of olive oil, fish, and vegetables.⁸⁷ Adherence to a Mediterranean diet also has been inversely correlated to the severity of acne vulgaris and hidradenitis suppurativa^88,89; however, these studies failed to account for the multifactorial risk factors associated with these conditions. Mediterranean diets also may impart a chemopreventive effect, supported by a number of in vivo and in vitro studies demonstrating the inhibition and/or reversal of cutaneous DNA damage induced by UV radiation through supplementation with various phytonutrients and omega-3 PUFAs.^81,90-92 Although small case-control studies have found a decreased risk of basal cell carcinoma in those who closely adhered to a Mediterranean diet, more rigorous clinical research is needed.⁹³

Whole-Food, Plant-Based Diet

A whole-food, plant-based (WFPB) diet is another popular dietary approach that consists of eating fruits, vegetables, legumes, nuts, seeds, and grains in their whole natural form.⁹⁴ This diet discourages all animal products, including red meat, seafood, dairy, and eggs. It is similar to a vegan diet except that it eliminates all highly refined carbohydrates, vegetable oils, and other processed foods.⁹⁴ Randomized clinical studies have demonstrated the WFPB diet to be effective in the treatment of obesity and metabolic syndrome.^95,96

A WFPB diet has been shown to increase the antioxidant capacity of cells, lengthen telomeres, and reduce formation of advanced glycation end products.^94,97,98 These benefits may help combat accelerated skin aging, including increased skin permeability, reduced elasticity and hydration, decreased angiogenesis, impaired immune function, and decreased vitamin D synthesis. Accelerated skin aging can result in delayed wound healing and susceptibility to skin tears and ecchymoses and also may promote the development of cutaneous malignancies.⁹⁹ There remains a lack of clinical data studying a properly formulated WFPB diet in the dermatologic setting.

Paleolithic Diet

The paleolithic (Paleo) diet is an increasingly popular way of eating that attempts to mirror what our ancestors may have consumed between 10,000 and 2.5 million years ago.¹⁰⁰ It is similar to the Mediterranean diet but excludes grains, dairy, legumes, and nightshade vegetables. It also calls for elimination of highly processed sugars and oils as well as chemical food additives and preservatives. There is a strict variation of the diet for individuals with autoimmune disease that also excludes eggs, nuts, and seeds, as these can be inflammatory or immunogenic in some patients.^100-106 Other variations of the diet exist, including the ketogenic Paleo diet, pegan (Paleo vegan) diet, and lacto-Paleo diet.¹⁰⁰ An often cited criticism of the Paleo diet is the low intake of calcium and risk for osteoporosis; however, consumption of calcium-rich foods or a calcium supplement can address this concern.¹⁰⁷

Although small clinical studies have found the Paleo diet to be beneficial for various autoimmune diseases, clinical data evaluating the utility of the diet for cutaneous disease is lacking.^108,109 Numerous randomized trials have demonstrated the Paleo diet to be effective for weight loss and improving insulin sensitivity and lipid levels.^110-116 Thus, the Paleo diet may theoretically serve as a viable adjunct dietary approach to the treatment of cutaneous diseases associated with obesity and metabolic derangement.¹¹⁷

Carnivore Diet

Arguably the most controversial and radical diet is the carnivore diet. As the name implies, the carnivore diet is based on consuming solely animal products. A properly structured carnivore diet emphasizes a “nose-to-tail” eating approach where all parts of the animal including the muscle meats, organs, and fat are consumed. Proponents of the diet cite anthropologic evidence from fossil-stable carbon-13/carbon-12 isotope analyses, craniodental features, and numerous other adaptations that indicate increased consumption of meat during human evolution.^118-122 Notably, many early humans ate a carnivore diet, but life span was very short at this time, suggesting the diet may not be as beneficial as has been suggested.

Despite the abundance of anecdotal evidence supporting its use for a variety of chronic conditions, including cutaneous autoimmune disease, there is a virtual absence of high-quality research on the carnivore diet.^123-125

The purported benefits of the carnivore diet may be attributed to the consumption of organ meats that contain highly bioavailable essential vitamins and minerals, such as iron, zinc, copper, selenium, thiamine, niacin, folate, vitamin B₆, vitamin B₁₂, vitamin A, vitamin D, vitamin K, and choline.^126-128 Other dietary compounds that have demonstrated benefit for skin health and are predominantly found in animal foods include carnosine, carnitine, creatine, taurine, coenzyme Q10, and collagen.^129-134 Nevertheless, there is no data to recommend the elimination of antioxidant- and micronutrient-dense plant-based foods. Rigorous clinical research evaluating the efficacy and safety of the carnivore diet in dermatologic patients is needed. A carnivore diet should not be undertaken without the assistance of a dietician who can ensure adequate micronutrient and macronutrient support.

Final Thoughts

The adjunctive role of diet in the treatment of skin disease is expanding and becoming more widely accepted among dermatologists. Unfortunately, there remains a lack of randomized controlled trials confirming the efficacy of various dietary interventions in the dermatologic setting. Although evidence-based dietary recommendations currently are limited, it is important for dermatologists to be aware of the varied and nuanced dietary interventions employed by patients.

Ultimately, dietary recommendations must be personalized, considering a patient’s comorbidities, personal beliefs and preferences, and nutrigenetics. The emerging field of dermatonutrigenomics—the study of how dietary compounds interact with one’s genes to influence skin health—may allow for precise dietary recommendations to be made in dermatologic practice. Direct-to-consumer genetic tests targeted toward dermatology patients are already on the market, but their clinical utility awaits validation.¹ Because nutritional science is a constantly evolving field, becoming familiar with these popular diets will serve both dermatologists and their patients well.

Within the last decade, almost 3000 articles have been published on the role of diet in the prevention and management of dermatologic conditions. Patients are increasingly interested in—and employing—dietary modifications that may influence skin appearance and aid in the treatment of cutaneous disease.¹ It is essential that dermatologists are familiar with existing evidence on the role of diet in dermatology to counsel patients appropriately. Herein, we discuss the compositions of several popular diets and their proposed utility for dermatologic purposes. We highlight the limited literature that exists surrounding this topic and emphasize the need for future, well-designed clinical trials that study the impact of diet on skin disease.

Ketogenic Diet

The ketogenic diet has a macronutrient profile composed of high fat, low to moderate protein, and very low carbohydrates. Nutritional ketosis occurs as the body begins to use free fatty acids (via beta oxidation) as the primary metabolite driving cellular metabolism. It has been suggested that the ketogenic diet may impart beneficial effects on skin disease; however, limited literature exists on the role of nutritional ketosis in the treatment of dermatologic conditions.

Mechanistically, the ketogenic diet decreases the secretion of insulin and insulinlike growth factor 1, resulting in a reduction of circulating androgens and increased activity of the retinoid X receptor.² In acne vulgaris, it has been suggested that the ketogenic diet may be beneficial in decreasing androgen-induced sebum production and the overproliferation of keratinocytes.^2-7 The ketogenic diet is one of the most rapidly effective dietary strategies for normalizing both insulin and androgens, thus it may theoretically be useful for other metabolic and hormone-dependent skin diseases, such as hidradenitis suppurativa.^8,9

The cutaneous manifestations associated with chronic hyperinsulinemia and hyperglycemia are numerous and include acanthosis nigricans, acrochordons, diabetic dermopathy, scleredema diabeticorum, bullosis diabeticorum, keratosis pilaris, and generalized granuloma annulare. There also is an increased risk for bacterial and fungal skin infections associated with hyperglycemic states.¹⁰ The ketogenic diet is an effective nonpharmacologic tool for normalizing serum insulin and glucose levels in most patients and may have utility in the aforementioned conditions.^11,12 In addition to improving insulin sensitivity, it has been used as a dietary strategy for weight loss.^11-15 Because obesity and metabolic syndrome are highly correlated with common skin conditions such as psoriasis, hidradenitis suppurativa, and androgenetic alopecia, there may be a role for employing the ketogenic diet in these patient populations.^16,17

Although robust clinical studies on ketogenic diets in skin disease are lacking, a recent single-arm, open-label clinical trial observed benefit in all 37 drug-naïve, overweight patients with chronic plaque psoriasis who underwent a ketogenic weight loss protocol. Significant reductions in psoriasis area and severity index (PASI) score and dermatology life quality index score were reported (P<.001).¹⁸ Another study of 30 patients with psoriasis found that a 4-week, low-calorie, ketogenic diet resulted in 50% improvement of PASI scores, 10% weight loss, and a reduction in the proinflammatory cytokines IL-1β and IL-2.¹⁹ Despite these results, it is a challenge to tease out if the specific dietary intervention or its associated weight loss was the main driver in these reported improvements in skin disease.

There is mixed evidence on the anti-inflammatory nature of the ketogenic diet, likely due to wide variation in the composition of foods included in individual diets. In many instances, the ketogenic diet is thought to possess considerable antioxidant and anti-inflammatory capabilities. Ketones are known activators of the nuclear factor erythroid 2–related factor 2 pathway, which upregulates the production of glutathione, a major endogenous intracellular antioxidant.²⁰ Additionally, dietary compounds from foods that are encouraged while on the ketogenic diet, such as sulforaphane from broccoli, also are independent activators of nuclear factor erythroid 2–related factor 2.²¹ Ketones are efficiently utilized by mitochondria, which also may result in the decreased production of reactive oxygen species and lower oxidative stress.²² Moreover, the ketone body β-hydroxybutyrate has demonstrated the ability to reduce proinflammatory IL-1β levels via suppression of nucleotide-binding domain-like receptor protein 3 inflammasome activity.^23,24 The activity of IL-1β is known to be elevated in many dermatologic conditions, including juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, hidradenitis suppurativa, Behçet disease, and other autoinflammatory syndromes.²⁵ Ketones also have been shown to inhibit the nuclear factor–κB proinflammatory signaling pathway.^22,26,27 Overexpression of IL-1β and aberrant activation of nuclear factor–κB are implicated in a variety of inflammatory, autoimmune, and oncologic cutaneous pathologies. The ketogenic diet may prove to be an effective adjunctive treatment for dermatologists to consider in select patient populations.^23,24,28-30

For patients with keratinocyte carcinomas, the ketogenic diet may offer the aforementioned anti-inflammatory and antioxidant effects, as well as suppression of the mechanistic target of rapamycin, a major regulator of cell metabolism and proliferation.^31,32 Inhibition of mechanistic target of rapamycin activity has been shown to slow tumor growth and reduce the development of squamous cell carcinoma.^25,33,34 The ketogenic diet also may exploit the preferential utilization of glucose exhibited by many types of cancer cells, thereby “starving” the tumor of its primary fuel source.^35,36 In vitro and animal studies in a variety of cancer types have demonstrated that a ketogenic metabolic state—achieved through the ketogenic diet or fasting—can sensitize tumor cells to chemotherapy and radiation while conferring a protective effect to normal cells.^37-40 This recently described phenomenon is known as differential stress resistance, but it has not been studied in keratinocyte malignancies or melanoma to date. Importantly, some basal cell carcinomas and BRAF V600E–mutated melanomas have worsened while on the ketogenic diet, suggesting more data is needed before it can be recommended for all cancer patients.^41,42 Furthermore, other skin conditions such as prurigo pigmentosa have been associated with initiation of the ketogenic diet.⁴³

Low FODMAP Diet

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that are poorly absorbed, osmotically active, and rapidly fermented by intestinal bacteria.⁴⁴ The low FODMAP diet has been shown to be efficacious for treatment of irritable bowel syndrome, small intestinal bacterial overgrowth (SIBO), and some cases of inflammatory bowel disease (IBD).^44-49 A low FODMAP diet may have potential implications for several dermatologic conditions.

Rosacea has been associated with various gastrointestinal tract disorders including irritable bowel syndrome, SIBO, and IBD.^50-54 A single study found that patients with rosacea had a 13-fold increased risk for SIBO.^55,56 Treatment of 40 patients with SIBO using rifaximin resulted in complete resolution of rosacea in all patients, with no relapse after a 3-year follow-up period.⁵⁵ Psoriasis also has been associated with SIBO and IBD.^57,58 One small study found that eradication of SIBO in psoriatic patients resulted in improved PASI scores and colorimetric values.⁵⁹

Although the long-term health consequences of the low FODMAP diet are unknown, further research on such dietary interventions for inflammatory skin conditions is warranted given the mounting evidence of a gut-skin connection and the role of the intestinal microbiome in skin health.^50,51

Gluten-Free Diet

Gluten is a protein found in a variety of grains. Although the role of gluten in the pathogenesis of celiac disease and dermatitis herpetiformis is indisputable, the deleterious effects of gluten outside of the context of these diseases remain controversial. There may be a compelling case for eliminating gluten in psoriasis patients with seropositivity for celiac disease. A recent systematic review found a 2.2-fold increased risk for celiac disease in psoriasis patients.⁶⁰ Antigliadin antibody titers also were found to be positively correlated with psoriatic disease severity.⁶¹ In addition, one open-label study found a reduction in PASI scores in 73% of patients with antigliadin antibodies after 3 months on a gluten-free diet compared to those without antibodies; however, the study only included 22 patients.⁶² Several other small studies have yielded similar results^63,64; however, antigliadin antibodies are neither the most sensitive nor specific markers of celiac disease, and additional testing should be completed in any patient who may carry this diagnosis. A survey study by the National Psoriasis Foundation found that the dietary change associated with the greatest skin improvement was removal of gluten and nightshade vegetables in approximately 50% of the 1200 psoriasis patients that responded.⁶⁵ Case reports of various dermatologic conditions including sarcoidosis, vitiligo, alopecia areata, lichen planus, dermatomyositis, pyoderma gangrenosum, erythema nodosum, leukocytoclastic vasculitis, linear IgA bullous dermatosis, and aphthous ulcerations have reportedly improved with a gluten-free diet; however, this should not be used as primary therapy in patients without celiac disease.^66-71 Because gluten-free diets can be expensive and challenging to follow, a formal assessment for celiac disease should be considered before recommendation of this dietary intervention.

Low Histamine Diet

Histamine is a biogenic amine produced by the decarboxylation of the amino acid histidine.⁷² It is found in several foods in varying amounts. Because bacteria can convert histidine into histamine, many fermented and aged foods such as kimchi, sauerkraut, cheese, and red wine contain high levels of histamine. Individuals who have decreased activity of diamine oxidase (DAO), an enzyme that degrades histamine, may be more susceptible to histamine intolerance.⁷² The symptoms of histamine intolerance are numerous and include gastrointestinal tract distress, rhinorrhea and nasal congestion, headache, urticaria, flushing, and pruritus. Histamine intolerance can mimic an IgE-mediated food allergy; however, allergy testing is negative in these patients. Unfortunately, there is no laboratory test for histamine intolerance; a double-blind, placebo-controlled food challenge is considered the gold-standard test.⁷²

As it pertains to dermatology, a low histamine diet may play a role in the treatment of certain patients with atopic dermatitis and chronic spontaneous urticaria. One study reported that 17 of 54 (31.5%) atopic patients had higher basal levels of serum histamine compared to controls.⁷³ Another study found that a histamine-free diet led to improvement in both histamine intolerance symptoms and atopic dermatitis disease severity (SCORing atopic dermatitis) in patients with low DAO activity.⁷⁴ In chronic spontaneous urticaria, a recent systematic review found that in 223 patients placed on a low histamine diet for 3 to 4 weeks, 12% and 44% achieved complete and partial remission, respectively.⁷⁵ Although treatment response based on a patient’s DAO activity level has not been correlated, a diet low in histamine may prove useful for patients with persistent atopic dermatitis and chronic spontaneous urticaria who have negative food allergy tests and report exacerbation of symptoms after ingestion of histamine-rich foods.^76,77

Mediterranean Diet

The Mediterranean diet has been touted as one of the healthiest diets to date, and large randomized clinical trials have demonstrated its effectiveness in weight loss, improving insulin sensitivity, and reducing inflammatory cytokine profiles.^78,79 A major criticism of the Mediterranean diet is that it has considerable ambiguity and lacks a precise definition due to the variability of what is consumed in different Mediterranean regions. Generally, the diet emphasizes high consumption of colorful fruits and vegetables, aromatic herbs and spices, olive oil, nuts, and seafood, as well as modest amounts of dairy, eggs, and red meat.⁸⁰ The anti-inflammatory effects of this diet largely have been attributed to its abundance of polyphenols, carotenoids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids (PUFAs).^80,81 Examples of polyphenols include resveratrol in red grapes, quercetin in apples and red onions, and curcumin in turmeric, while examples of carotenoids include lycopene in tomatoes and zeaxanthin in dark leafy greens. Oleic acid is a monounsaturated fatty acid present in high concentrations in olive oil, while eicosapentaenoic acid and docosahexaenoic acid are omega-3 PUFAs predominantly found in fish.⁸²

Unfortunately, rigorous clinical trials regarding the Mediterranean diet as it pertains to dermatology have not been undertaken. Numerous observational studies in patients with psoriasis have suggested that close adherence to the Mediterranean diet was associated with improvement in PASI scores.^83-86 The National Psoriasis Foundation now recommends a trial of the Mediterranean diet in some patients with psoriasis, emphasizing increased dietary intake of olive oil, fish, and vegetables.⁸⁷ Adherence to a Mediterranean diet also has been inversely correlated to the severity of acne vulgaris and hidradenitis suppurativa^88,89; however, these studies failed to account for the multifactorial risk factors associated with these conditions. Mediterranean diets also may impart a chemopreventive effect, supported by a number of in vivo and in vitro studies demonstrating the inhibition and/or reversal of cutaneous DNA damage induced by UV radiation through supplementation with various phytonutrients and omega-3 PUFAs.^81,90-92 Although small case-control studies have found a decreased risk of basal cell carcinoma in those who closely adhered to a Mediterranean diet, more rigorous clinical research is needed.⁹³

Whole-Food, Plant-Based Diet

A whole-food, plant-based (WFPB) diet is another popular dietary approach that consists of eating fruits, vegetables, legumes, nuts, seeds, and grains in their whole natural form.⁹⁴ This diet discourages all animal products, including red meat, seafood, dairy, and eggs. It is similar to a vegan diet except that it eliminates all highly refined carbohydrates, vegetable oils, and other processed foods.⁹⁴ Randomized clinical studies have demonstrated the WFPB diet to be effective in the treatment of obesity and metabolic syndrome.^95,96

A WFPB diet has been shown to increase the antioxidant capacity of cells, lengthen telomeres, and reduce formation of advanced glycation end products.^94,97,98 These benefits may help combat accelerated skin aging, including increased skin permeability, reduced elasticity and hydration, decreased angiogenesis, impaired immune function, and decreased vitamin D synthesis. Accelerated skin aging can result in delayed wound healing and susceptibility to skin tears and ecchymoses and also may promote the development of cutaneous malignancies.⁹⁹ There remains a lack of clinical data studying a properly formulated WFPB diet in the dermatologic setting.

Paleolithic Diet

The paleolithic (Paleo) diet is an increasingly popular way of eating that attempts to mirror what our ancestors may have consumed between 10,000 and 2.5 million years ago.¹⁰⁰ It is similar to the Mediterranean diet but excludes grains, dairy, legumes, and nightshade vegetables. It also calls for elimination of highly processed sugars and oils as well as chemical food additives and preservatives. There is a strict variation of the diet for individuals with autoimmune disease that also excludes eggs, nuts, and seeds, as these can be inflammatory or immunogenic in some patients.^100-106 Other variations of the diet exist, including the ketogenic Paleo diet, pegan (Paleo vegan) diet, and lacto-Paleo diet.¹⁰⁰ An often cited criticism of the Paleo diet is the low intake of calcium and risk for osteoporosis; however, consumption of calcium-rich foods or a calcium supplement can address this concern.¹⁰⁷

Although small clinical studies have found the Paleo diet to be beneficial for various autoimmune diseases, clinical data evaluating the utility of the diet for cutaneous disease is lacking.^108,109 Numerous randomized trials have demonstrated the Paleo diet to be effective for weight loss and improving insulin sensitivity and lipid levels.^110-116 Thus, the Paleo diet may theoretically serve as a viable adjunct dietary approach to the treatment of cutaneous diseases associated with obesity and metabolic derangement.¹¹⁷

Carnivore Diet

Arguably the most controversial and radical diet is the carnivore diet. As the name implies, the carnivore diet is based on consuming solely animal products. A properly structured carnivore diet emphasizes a “nose-to-tail” eating approach where all parts of the animal including the muscle meats, organs, and fat are consumed. Proponents of the diet cite anthropologic evidence from fossil-stable carbon-13/carbon-12 isotope analyses, craniodental features, and numerous other adaptations that indicate increased consumption of meat during human evolution.^118-122 Notably, many early humans ate a carnivore diet, but life span was very short at this time, suggesting the diet may not be as beneficial as has been suggested.

Despite the abundance of anecdotal evidence supporting its use for a variety of chronic conditions, including cutaneous autoimmune disease, there is a virtual absence of high-quality research on the carnivore diet.^123-125

The purported benefits of the carnivore diet may be attributed to the consumption of organ meats that contain highly bioavailable essential vitamins and minerals, such as iron, zinc, copper, selenium, thiamine, niacin, folate, vitamin B₆, vitamin B₁₂, vitamin A, vitamin D, vitamin K, and choline.^126-128 Other dietary compounds that have demonstrated benefit for skin health and are predominantly found in animal foods include carnosine, carnitine, creatine, taurine, coenzyme Q10, and collagen.^129-134 Nevertheless, there is no data to recommend the elimination of antioxidant- and micronutrient-dense plant-based foods. Rigorous clinical research evaluating the efficacy and safety of the carnivore diet in dermatologic patients is needed. A carnivore diet should not be undertaken without the assistance of a dietician who can ensure adequate micronutrient and macronutrient support.

Final Thoughts

The adjunctive role of diet in the treatment of skin disease is expanding and becoming more widely accepted among dermatologists. Unfortunately, there remains a lack of randomized controlled trials confirming the efficacy of various dietary interventions in the dermatologic setting. Although evidence-based dietary recommendations currently are limited, it is important for dermatologists to be aware of the varied and nuanced dietary interventions employed by patients.

Ultimately, dietary recommendations must be personalized, considering a patient’s comorbidities, personal beliefs and preferences, and nutrigenetics. The emerging field of dermatonutrigenomics—the study of how dietary compounds interact with one’s genes to influence skin health—may allow for precise dietary recommendations to be made in dermatologic practice. Direct-to-consumer genetic tests targeted toward dermatology patients are already on the market, but their clinical utility awaits validation.¹ Because nutritional science is a constantly evolving field, becoming familiar with these popular diets will serve both dermatologists and their patients well.

Within the last decade, almost 3000 articles have been published on the role of diet in the prevention and management of dermatologic conditions. Patients are increasingly interested in—and employing—dietary modifications that may influence skin appearance and aid in the treatment of cutaneous disease.¹ It is essential that dermatologists are familiar with existing evidence on the role of diet in dermatology to counsel patients appropriately. Herein, we discuss the compositions of several popular diets and their proposed utility for dermatologic purposes. We highlight the limited literature that exists surrounding this topic and emphasize the need for future, well-designed clinical trials that study the impact of diet on skin disease.

Ketogenic Diet

The ketogenic diet has a macronutrient profile composed of high fat, low to moderate protein, and very low carbohydrates. Nutritional ketosis occurs as the body begins to use free fatty acids (via beta oxidation) as the primary metabolite driving cellular metabolism. It has been suggested that the ketogenic diet may impart beneficial effects on skin disease; however, limited literature exists on the role of nutritional ketosis in the treatment of dermatologic conditions.

Mechanistically, the ketogenic diet decreases the secretion of insulin and insulinlike growth factor 1, resulting in a reduction of circulating androgens and increased activity of the retinoid X receptor.² In acne vulgaris, it has been suggested that the ketogenic diet may be beneficial in decreasing androgen-induced sebum production and the overproliferation of keratinocytes.^2-7 The ketogenic diet is one of the most rapidly effective dietary strategies for normalizing both insulin and androgens, thus it may theoretically be useful for other metabolic and hormone-dependent skin diseases, such as hidradenitis suppurativa.^8,9

The cutaneous manifestations associated with chronic hyperinsulinemia and hyperglycemia are numerous and include acanthosis nigricans, acrochordons, diabetic dermopathy, scleredema diabeticorum, bullosis diabeticorum, keratosis pilaris, and generalized granuloma annulare. There also is an increased risk for bacterial and fungal skin infections associated with hyperglycemic states.¹⁰ The ketogenic diet is an effective nonpharmacologic tool for normalizing serum insulin and glucose levels in most patients and may have utility in the aforementioned conditions.^11,12 In addition to improving insulin sensitivity, it has been used as a dietary strategy for weight loss.^11-15 Because obesity and metabolic syndrome are highly correlated with common skin conditions such as psoriasis, hidradenitis suppurativa, and androgenetic alopecia, there may be a role for employing the ketogenic diet in these patient populations.^16,17

Although robust clinical studies on ketogenic diets in skin disease are lacking, a recent single-arm, open-label clinical trial observed benefit in all 37 drug-naïve, overweight patients with chronic plaque psoriasis who underwent a ketogenic weight loss protocol. Significant reductions in psoriasis area and severity index (PASI) score and dermatology life quality index score were reported (P<.001).¹⁸ Another study of 30 patients with psoriasis found that a 4-week, low-calorie, ketogenic diet resulted in 50% improvement of PASI scores, 10% weight loss, and a reduction in the proinflammatory cytokines IL-1β and IL-2.¹⁹ Despite these results, it is a challenge to tease out if the specific dietary intervention or its associated weight loss was the main driver in these reported improvements in skin disease.

There is mixed evidence on the anti-inflammatory nature of the ketogenic diet, likely due to wide variation in the composition of foods included in individual diets. In many instances, the ketogenic diet is thought to possess considerable antioxidant and anti-inflammatory capabilities. Ketones are known activators of the nuclear factor erythroid 2–related factor 2 pathway, which upregulates the production of glutathione, a major endogenous intracellular antioxidant.²⁰ Additionally, dietary compounds from foods that are encouraged while on the ketogenic diet, such as sulforaphane from broccoli, also are independent activators of nuclear factor erythroid 2–related factor 2.²¹ Ketones are efficiently utilized by mitochondria, which also may result in the decreased production of reactive oxygen species and lower oxidative stress.²² Moreover, the ketone body β-hydroxybutyrate has demonstrated the ability to reduce proinflammatory IL-1β levels via suppression of nucleotide-binding domain-like receptor protein 3 inflammasome activity.^23,24 The activity of IL-1β is known to be elevated in many dermatologic conditions, including juvenile idiopathic arthritis, relapsing polychondritis, Schnitzler syndrome, hidradenitis suppurativa, Behçet disease, and other autoinflammatory syndromes.²⁵ Ketones also have been shown to inhibit the nuclear factor–κB proinflammatory signaling pathway.^22,26,27 Overexpression of IL-1β and aberrant activation of nuclear factor–κB are implicated in a variety of inflammatory, autoimmune, and oncologic cutaneous pathologies. The ketogenic diet may prove to be an effective adjunctive treatment for dermatologists to consider in select patient populations.^23,24,28-30

For patients with keratinocyte carcinomas, the ketogenic diet may offer the aforementioned anti-inflammatory and antioxidant effects, as well as suppression of the mechanistic target of rapamycin, a major regulator of cell metabolism and proliferation.^31,32 Inhibition of mechanistic target of rapamycin activity has been shown to slow tumor growth and reduce the development of squamous cell carcinoma.^25,33,34 The ketogenic diet also may exploit the preferential utilization of glucose exhibited by many types of cancer cells, thereby “starving” the tumor of its primary fuel source.^35,36 In vitro and animal studies in a variety of cancer types have demonstrated that a ketogenic metabolic state—achieved through the ketogenic diet or fasting—can sensitize tumor cells to chemotherapy and radiation while conferring a protective effect to normal cells.^37-40 This recently described phenomenon is known as differential stress resistance, but it has not been studied in keratinocyte malignancies or melanoma to date. Importantly, some basal cell carcinomas and BRAF V600E–mutated melanomas have worsened while on the ketogenic diet, suggesting more data is needed before it can be recommended for all cancer patients.^41,42 Furthermore, other skin conditions such as prurigo pigmentosa have been associated with initiation of the ketogenic diet.⁴³

Low FODMAP Diet

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are short-chain carbohydrates that are poorly absorbed, osmotically active, and rapidly fermented by intestinal bacteria.⁴⁴ The low FODMAP diet has been shown to be efficacious for treatment of irritable bowel syndrome, small intestinal bacterial overgrowth (SIBO), and some cases of inflammatory bowel disease (IBD).^44-49 A low FODMAP diet may have potential implications for several dermatologic conditions.

Rosacea has been associated with various gastrointestinal tract disorders including irritable bowel syndrome, SIBO, and IBD.^50-54 A single study found that patients with rosacea had a 13-fold increased risk for SIBO.^55,56 Treatment of 40 patients with SIBO using rifaximin resulted in complete resolution of rosacea in all patients, with no relapse after a 3-year follow-up period.⁵⁵ Psoriasis also has been associated with SIBO and IBD.^57,58 One small study found that eradication of SIBO in psoriatic patients resulted in improved PASI scores and colorimetric values.⁵⁹

Although the long-term health consequences of the low FODMAP diet are unknown, further research on such dietary interventions for inflammatory skin conditions is warranted given the mounting evidence of a gut-skin connection and the role of the intestinal microbiome in skin health.^50,51

Gluten-Free Diet

Gluten is a protein found in a variety of grains. Although the role of gluten in the pathogenesis of celiac disease and dermatitis herpetiformis is indisputable, the deleterious effects of gluten outside of the context of these diseases remain controversial. There may be a compelling case for eliminating gluten in psoriasis patients with seropositivity for celiac disease. A recent systematic review found a 2.2-fold increased risk for celiac disease in psoriasis patients.⁶⁰ Antigliadin antibody titers also were found to be positively correlated with psoriatic disease severity.⁶¹ In addition, one open-label study found a reduction in PASI scores in 73% of patients with antigliadin antibodies after 3 months on a gluten-free diet compared to those without antibodies; however, the study only included 22 patients.⁶² Several other small studies have yielded similar results^63,64; however, antigliadin antibodies are neither the most sensitive nor specific markers of celiac disease, and additional testing should be completed in any patient who may carry this diagnosis. A survey study by the National Psoriasis Foundation found that the dietary change associated with the greatest skin improvement was removal of gluten and nightshade vegetables in approximately 50% of the 1200 psoriasis patients that responded.⁶⁵ Case reports of various dermatologic conditions including sarcoidosis, vitiligo, alopecia areata, lichen planus, dermatomyositis, pyoderma gangrenosum, erythema nodosum, leukocytoclastic vasculitis, linear IgA bullous dermatosis, and aphthous ulcerations have reportedly improved with a gluten-free diet; however, this should not be used as primary therapy in patients without celiac disease.^66-71 Because gluten-free diets can be expensive and challenging to follow, a formal assessment for celiac disease should be considered before recommendation of this dietary intervention.

Low Histamine Diet

Histamine is a biogenic amine produced by the decarboxylation of the amino acid histidine.⁷² It is found in several foods in varying amounts. Because bacteria can convert histidine into histamine, many fermented and aged foods such as kimchi, sauerkraut, cheese, and red wine contain high levels of histamine. Individuals who have decreased activity of diamine oxidase (DAO), an enzyme that degrades histamine, may be more susceptible to histamine intolerance.⁷² The symptoms of histamine intolerance are numerous and include gastrointestinal tract distress, rhinorrhea and nasal congestion, headache, urticaria, flushing, and pruritus. Histamine intolerance can mimic an IgE-mediated food allergy; however, allergy testing is negative in these patients. Unfortunately, there is no laboratory test for histamine intolerance; a double-blind, placebo-controlled food challenge is considered the gold-standard test.⁷²

As it pertains to dermatology, a low histamine diet may play a role in the treatment of certain patients with atopic dermatitis and chronic spontaneous urticaria. One study reported that 17 of 54 (31.5%) atopic patients had higher basal levels of serum histamine compared to controls.⁷³ Another study found that a histamine-free diet led to improvement in both histamine intolerance symptoms and atopic dermatitis disease severity (SCORing atopic dermatitis) in patients with low DAO activity.⁷⁴ In chronic spontaneous urticaria, a recent systematic review found that in 223 patients placed on a low histamine diet for 3 to 4 weeks, 12% and 44% achieved complete and partial remission, respectively.⁷⁵ Although treatment response based on a patient’s DAO activity level has not been correlated, a diet low in histamine may prove useful for patients with persistent atopic dermatitis and chronic spontaneous urticaria who have negative food allergy tests and report exacerbation of symptoms after ingestion of histamine-rich foods.^76,77

Mediterranean Diet

The Mediterranean diet has been touted as one of the healthiest diets to date, and large randomized clinical trials have demonstrated its effectiveness in weight loss, improving insulin sensitivity, and reducing inflammatory cytokine profiles.^78,79 A major criticism of the Mediterranean diet is that it has considerable ambiguity and lacks a precise definition due to the variability of what is consumed in different Mediterranean regions. Generally, the diet emphasizes high consumption of colorful fruits and vegetables, aromatic herbs and spices, olive oil, nuts, and seafood, as well as modest amounts of dairy, eggs, and red meat.⁸⁰ The anti-inflammatory effects of this diet largely have been attributed to its abundance of polyphenols, carotenoids, monounsaturated fatty acids, and omega-3 polyunsaturated fatty acids (PUFAs).^80,81 Examples of polyphenols include resveratrol in red grapes, quercetin in apples and red onions, and curcumin in turmeric, while examples of carotenoids include lycopene in tomatoes and zeaxanthin in dark leafy greens. Oleic acid is a monounsaturated fatty acid present in high concentrations in olive oil, while eicosapentaenoic acid and docosahexaenoic acid are omega-3 PUFAs predominantly found in fish.⁸²

Unfortunately, rigorous clinical trials regarding the Mediterranean diet as it pertains to dermatology have not been undertaken. Numerous observational studies in patients with psoriasis have suggested that close adherence to the Mediterranean diet was associated with improvement in PASI scores.^83-86 The National Psoriasis Foundation now recommends a trial of the Mediterranean diet in some patients with psoriasis, emphasizing increased dietary intake of olive oil, fish, and vegetables.⁸⁷ Adherence to a Mediterranean diet also has been inversely correlated to the severity of acne vulgaris and hidradenitis suppurativa^88,89; however, these studies failed to account for the multifactorial risk factors associated with these conditions. Mediterranean diets also may impart a chemopreventive effect, supported by a number of in vivo and in vitro studies demonstrating the inhibition and/or reversal of cutaneous DNA damage induced by UV radiation through supplementation with various phytonutrients and omega-3 PUFAs.^81,90-92 Although small case-control studies have found a decreased risk of basal cell carcinoma in those who closely adhered to a Mediterranean diet, more rigorous clinical research is needed.⁹³

Whole-Food, Plant-Based Diet

A whole-food, plant-based (WFPB) diet is another popular dietary approach that consists of eating fruits, vegetables, legumes, nuts, seeds, and grains in their whole natural form.⁹⁴ This diet discourages all animal products, including red meat, seafood, dairy, and eggs. It is similar to a vegan diet except that it eliminates all highly refined carbohydrates, vegetable oils, and other processed foods.⁹⁴ Randomized clinical studies have demonstrated the WFPB diet to be effective in the treatment of obesity and metabolic syndrome.^95,96

A WFPB diet has been shown to increase the antioxidant capacity of cells, lengthen telomeres, and reduce formation of advanced glycation end products.^94,97,98 These benefits may help combat accelerated skin aging, including increased skin permeability, reduced elasticity and hydration, decreased angiogenesis, impaired immune function, and decreased vitamin D synthesis. Accelerated skin aging can result in delayed wound healing and susceptibility to skin tears and ecchymoses and also may promote the development of cutaneous malignancies.⁹⁹ There remains a lack of clinical data studying a properly formulated WFPB diet in the dermatologic setting.

Paleolithic Diet

The paleolithic (Paleo) diet is an increasingly popular way of eating that attempts to mirror what our ancestors may have consumed between 10,000 and 2.5 million years ago.¹⁰⁰ It is similar to the Mediterranean diet but excludes grains, dairy, legumes, and nightshade vegetables. It also calls for elimination of highly processed sugars and oils as well as chemical food additives and preservatives. There is a strict variation of the diet for individuals with autoimmune disease that also excludes eggs, nuts, and seeds, as these can be inflammatory or immunogenic in some patients.^100-106 Other variations of the diet exist, including the ketogenic Paleo diet, pegan (Paleo vegan) diet, and lacto-Paleo diet.¹⁰⁰ An often cited criticism of the Paleo diet is the low intake of calcium and risk for osteoporosis; however, consumption of calcium-rich foods or a calcium supplement can address this concern.¹⁰⁷

Although small clinical studies have found the Paleo diet to be beneficial for various autoimmune diseases, clinical data evaluating the utility of the diet for cutaneous disease is lacking.^108,109 Numerous randomized trials have demonstrated the Paleo diet to be effective for weight loss and improving insulin sensitivity and lipid levels.^110-116 Thus, the Paleo diet may theoretically serve as a viable adjunct dietary approach to the treatment of cutaneous diseases associated with obesity and metabolic derangement.¹¹⁷

Carnivore Diet

Arguably the most controversial and radical diet is the carnivore diet. As the name implies, the carnivore diet is based on consuming solely animal products. A properly structured carnivore diet emphasizes a “nose-to-tail” eating approach where all parts of the animal including the muscle meats, organs, and fat are consumed. Proponents of the diet cite anthropologic evidence from fossil-stable carbon-13/carbon-12 isotope analyses, craniodental features, and numerous other adaptations that indicate increased consumption of meat during human evolution.^118-122 Notably, many early humans ate a carnivore diet, but life span was very short at this time, suggesting the diet may not be as beneficial as has been suggested.

Despite the abundance of anecdotal evidence supporting its use for a variety of chronic conditions, including cutaneous autoimmune disease, there is a virtual absence of high-quality research on the carnivore diet.^123-125

The purported benefits of the carnivore diet may be attributed to the consumption of organ meats that contain highly bioavailable essential vitamins and minerals, such as iron, zinc, copper, selenium, thiamine, niacin, folate, vitamin B₆, vitamin B₁₂, vitamin A, vitamin D, vitamin K, and choline.^126-128 Other dietary compounds that have demonstrated benefit for skin health and are predominantly found in animal foods include carnosine, carnitine, creatine, taurine, coenzyme Q10, and collagen.^129-134 Nevertheless, there is no data to recommend the elimination of antioxidant- and micronutrient-dense plant-based foods. Rigorous clinical research evaluating the efficacy and safety of the carnivore diet in dermatologic patients is needed. A carnivore diet should not be undertaken without the assistance of a dietician who can ensure adequate micronutrient and macronutrient support.

Final Thoughts

The adjunctive role of diet in the treatment of skin disease is expanding and becoming more widely accepted among dermatologists. Unfortunately, there remains a lack of randomized controlled trials confirming the efficacy of various dietary interventions in the dermatologic setting. Although evidence-based dietary recommendations currently are limited, it is important for dermatologists to be aware of the varied and nuanced dietary interventions employed by patients.

Ultimately, dietary recommendations must be personalized, considering a patient’s comorbidities, personal beliefs and preferences, and nutrigenetics. The emerging field of dermatonutrigenomics—the study of how dietary compounds interact with one’s genes to influence skin health—may allow for precise dietary recommendations to be made in dermatologic practice. Direct-to-consumer genetic tests targeted toward dermatology patients are already on the market, but their clinical utility awaits validation.¹ Because nutritional science is a constantly evolving field, becoming familiar with these popular diets will serve both dermatologists and their patients well.

Effective on January 1, 2021, the outpatient evaluation and management (E/M) codes underwent substantial changes, which were the culmination of multiple years of revision and surveying via the American Medical Association (AMA) Relative Value Scale Update Committee and Current Procedural Terminology (RUC-CPT) process to streamline definitions and promote consistency as well as to decrease the administrative burden for all specialties within the house of medicine.¹ These updates represent a notable change from the previous documentation requirements for this oft used family of codes. Herein, we break down some of the highlights of the changes and how they may be applied for some commonly used dermatologic diagnoses.

Time Is Time Is Time

Prior to the 2021 revisions, a physician generally could only code for an E/M level by time for a face-to-face encounter dominated by counseling and/or care coordination. With the new updates, any encounter can be coded by total time spent by the physician with the patient¹; however, clinical staff time is not included. There also are now clear guidelines of the time ranges corresponding to the level of E/M,¹ as noted in Table 1.

Importantly, time now includes not just face-to-face time with the patient but also any time on the date of the encounter that the physician is involved in the care of the patient when not reported with a separate code. This can include reviewing notes or data before or after the examination, care coordination, ordering laboratory tests, and providing any documentation related to the encounter. Importantly, this applies only when these activities are done on the date of the encounter.

If you work with a nurse practitioner or physician assistant (PA) who assists you and you are the one reporting the service, you cannot double-dip. For example, if your PA spends 10 minutes alone with a patient, you are in the room together for 5 minutes, the PA spends another 10 minutes alone with the patient afterward, and you do chart work for 10 minutes at the end of the day, the total time spent is 35 minutes, not 40 minutes, as you cannot count the time you and the PA spent together twice.

Decisions, Decisions

Evaluation and management coding also can be determined via the level of medical decision-making (MDM). Per the 2021 guidelines, MDM is comprised of 3 categories: (1) number and complexity of problems addressed at the encounter, (2) amount and/or complexity of data to be reviewed or analyzed, and (3) risk of complications and/or morbidity or mortality of patient management.¹ To reach a certain overall E/M level, 2 of 3 categories must be met or exceeded. Let’s dive into each of these in a little more detail.

Number and Complexity of Problems Addressed at the Encounter
First, it is important to understand the definition of a problem addressed. Per AMA guidelines, this includes a disease, condition, illness, injury, symptom, sign, finding, complaint, or other matter addressed at the encounter that is evaluated or treated at the encounter by the physician. If the problem is referred to another provider without evaluation or consideration of treatment, it is not considered to be a problem addressed and cannot count toward this first category. An example could be a patient with a lump on the abdomen that you refer to plastic or general surgery for evaluation and treatment.

Once you have determined that you are addressing a problem, you will need to determine the level of complexity of the problem, as outlined in Table 2. Keep in mind that some entities and disease states in dermatology may fit the requirements of more than 1 level of complexity depending on the clinical situation, while there are many entities in dermatology that may not be perfectly captured by any of the levels described. In these situations, clinical judgement is required to determine where the problem would best fit. Importantly, whatever you decide, your documentation should support that decision.

Putting It All Together

Once you have determined each of the above 3 categories, you can put them together into the MDM chart to ascertain the overall level of MDM. (The official AMA medical decision-making grid is available online [https://www.ama-assn.org/system/files/2019-06/cpt-revised-mdm-grid.pdf]). Keep in mind that 2 of 3 columns in the table must be obtained in that level to reach an overall E/M level; for example, a visit that addresses 2 self-limited or minor problems (level 3) in which no data is reviewed (level 2) and involves prescribing a new medication (level 4), would be an overall level 3 visit.

Final Thoughts

The outpatient E/M guidelines have undergone substantial revisions; therefore, it is crucial to understand the updated definitions to ensure proper billing and documentation. History and physical examination documentation must be medically appropriate but are no longer used to determine overall E/M level; time and MDM are the sole options that can be used. Importantly, try to code as accurately as possible, documenting which problems were both noted and addressed. If you are unsure of a definition within the updated changes and MDM table, referencing the appropriate sources for guidance is recommended.

Although representing a considerable shift, the revaluation of this family of codes and the intended decrease in documentation burden has the ability to be a positive gain for dermatologists. Expect other code families to mirror these changes in the next few years.

Effective on January 1, 2021, the outpatient evaluation and management (E/M) codes underwent substantial changes, which were the culmination of multiple years of revision and surveying via the American Medical Association (AMA) Relative Value Scale Update Committee and Current Procedural Terminology (RUC-CPT) process to streamline definitions and promote consistency as well as to decrease the administrative burden for all specialties within the house of medicine.¹ These updates represent a notable change from the previous documentation requirements for this oft used family of codes. Herein, we break down some of the highlights of the changes and how they may be applied for some commonly used dermatologic diagnoses.

Time Is Time Is Time

Prior to the 2021 revisions, a physician generally could only code for an E/M level by time for a face-to-face encounter dominated by counseling and/or care coordination. With the new updates, any encounter can be coded by total time spent by the physician with the patient¹; however, clinical staff time is not included. There also are now clear guidelines of the time ranges corresponding to the level of E/M,¹ as noted in Table 1.

Importantly, time now includes not just face-to-face time with the patient but also any time on the date of the encounter that the physician is involved in the care of the patient when not reported with a separate code. This can include reviewing notes or data before or after the examination, care coordination, ordering laboratory tests, and providing any documentation related to the encounter. Importantly, this applies only when these activities are done on the date of the encounter.

If you work with a nurse practitioner or physician assistant (PA) who assists you and you are the one reporting the service, you cannot double-dip. For example, if your PA spends 10 minutes alone with a patient, you are in the room together for 5 minutes, the PA spends another 10 minutes alone with the patient afterward, and you do chart work for 10 minutes at the end of the day, the total time spent is 35 minutes, not 40 minutes, as you cannot count the time you and the PA spent together twice.

Decisions, Decisions

Evaluation and management coding also can be determined via the level of medical decision-making (MDM). Per the 2021 guidelines, MDM is comprised of 3 categories: (1) number and complexity of problems addressed at the encounter, (2) amount and/or complexity of data to be reviewed or analyzed, and (3) risk of complications and/or morbidity or mortality of patient management.¹ To reach a certain overall E/M level, 2 of 3 categories must be met or exceeded. Let’s dive into each of these in a little more detail.

Number and Complexity of Problems Addressed at the Encounter
First, it is important to understand the definition of a problem addressed. Per AMA guidelines, this includes a disease, condition, illness, injury, symptom, sign, finding, complaint, or other matter addressed at the encounter that is evaluated or treated at the encounter by the physician. If the problem is referred to another provider without evaluation or consideration of treatment, it is not considered to be a problem addressed and cannot count toward this first category. An example could be a patient with a lump on the abdomen that you refer to plastic or general surgery for evaluation and treatment.

Once you have determined that you are addressing a problem, you will need to determine the level of complexity of the problem, as outlined in Table 2. Keep in mind that some entities and disease states in dermatology may fit the requirements of more than 1 level of complexity depending on the clinical situation, while there are many entities in dermatology that may not be perfectly captured by any of the levels described. In these situations, clinical judgement is required to determine where the problem would best fit. Importantly, whatever you decide, your documentation should support that decision.

Putting It All Together

Once you have determined each of the above 3 categories, you can put them together into the MDM chart to ascertain the overall level of MDM. (The official AMA medical decision-making grid is available online [https://www.ama-assn.org/system/files/2019-06/cpt-revised-mdm-grid.pdf]). Keep in mind that 2 of 3 columns in the table must be obtained in that level to reach an overall E/M level; for example, a visit that addresses 2 self-limited or minor problems (level 3) in which no data is reviewed (level 2) and involves prescribing a new medication (level 4), would be an overall level 3 visit.

Final Thoughts

The outpatient E/M guidelines have undergone substantial revisions; therefore, it is crucial to understand the updated definitions to ensure proper billing and documentation. History and physical examination documentation must be medically appropriate but are no longer used to determine overall E/M level; time and MDM are the sole options that can be used. Importantly, try to code as accurately as possible, documenting which problems were both noted and addressed. If you are unsure of a definition within the updated changes and MDM table, referencing the appropriate sources for guidance is recommended.

Although representing a considerable shift, the revaluation of this family of codes and the intended decrease in documentation burden has the ability to be a positive gain for dermatologists. Expect other code families to mirror these changes in the next few years.

Effective on January 1, 2021, the outpatient evaluation and management (E/M) codes underwent substantial changes, which were the culmination of multiple years of revision and surveying via the American Medical Association (AMA) Relative Value Scale Update Committee and Current Procedural Terminology (RUC-CPT) process to streamline definitions and promote consistency as well as to decrease the administrative burden for all specialties within the house of medicine.¹ These updates represent a notable change from the previous documentation requirements for this oft used family of codes. Herein, we break down some of the highlights of the changes and how they may be applied for some commonly used dermatologic diagnoses.

Time Is Time Is Time

Prior to the 2021 revisions, a physician generally could only code for an E/M level by time for a face-to-face encounter dominated by counseling and/or care coordination. With the new updates, any encounter can be coded by total time spent by the physician with the patient¹; however, clinical staff time is not included. There also are now clear guidelines of the time ranges corresponding to the level of E/M,¹ as noted in Table 1.

Importantly, time now includes not just face-to-face time with the patient but also any time on the date of the encounter that the physician is involved in the care of the patient when not reported with a separate code. This can include reviewing notes or data before or after the examination, care coordination, ordering laboratory tests, and providing any documentation related to the encounter. Importantly, this applies only when these activities are done on the date of the encounter.

If you work with a nurse practitioner or physician assistant (PA) who assists you and you are the one reporting the service, you cannot double-dip. For example, if your PA spends 10 minutes alone with a patient, you are in the room together for 5 minutes, the PA spends another 10 minutes alone with the patient afterward, and you do chart work for 10 minutes at the end of the day, the total time spent is 35 minutes, not 40 minutes, as you cannot count the time you and the PA spent together twice.

Decisions, Decisions

Evaluation and management coding also can be determined via the level of medical decision-making (MDM). Per the 2021 guidelines, MDM is comprised of 3 categories: (1) number and complexity of problems addressed at the encounter, (2) amount and/or complexity of data to be reviewed or analyzed, and (3) risk of complications and/or morbidity or mortality of patient management.¹ To reach a certain overall E/M level, 2 of 3 categories must be met or exceeded. Let’s dive into each of these in a little more detail.

Number and Complexity of Problems Addressed at the Encounter
First, it is important to understand the definition of a problem addressed. Per AMA guidelines, this includes a disease, condition, illness, injury, symptom, sign, finding, complaint, or other matter addressed at the encounter that is evaluated or treated at the encounter by the physician. If the problem is referred to another provider without evaluation or consideration of treatment, it is not considered to be a problem addressed and cannot count toward this first category. An example could be a patient with a lump on the abdomen that you refer to plastic or general surgery for evaluation and treatment.

Once you have determined that you are addressing a problem, you will need to determine the level of complexity of the problem, as outlined in Table 2. Keep in mind that some entities and disease states in dermatology may fit the requirements of more than 1 level of complexity depending on the clinical situation, while there are many entities in dermatology that may not be perfectly captured by any of the levels described. In these situations, clinical judgement is required to determine where the problem would best fit. Importantly, whatever you decide, your documentation should support that decision.

Putting It All Together

Once you have determined each of the above 3 categories, you can put them together into the MDM chart to ascertain the overall level of MDM. (The official AMA medical decision-making grid is available online [https://www.ama-assn.org/system/files/2019-06/cpt-revised-mdm-grid.pdf]). Keep in mind that 2 of 3 columns in the table must be obtained in that level to reach an overall E/M level; for example, a visit that addresses 2 self-limited or minor problems (level 3) in which no data is reviewed (level 2) and involves prescribing a new medication (level 4), would be an overall level 3 visit.

Final Thoughts

The outpatient E/M guidelines have undergone substantial revisions; therefore, it is crucial to understand the updated definitions to ensure proper billing and documentation. History and physical examination documentation must be medically appropriate but are no longer used to determine overall E/M level; time and MDM are the sole options that can be used. Importantly, try to code as accurately as possible, documenting which problems were both noted and addressed. If you are unsure of a definition within the updated changes and MDM table, referencing the appropriate sources for guidance is recommended.

Although representing a considerable shift, the revaluation of this family of codes and the intended decrease in documentation burden has the ability to be a positive gain for dermatologists. Expect other code families to mirror these changes in the next few years.

As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.¹ Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.

Cutaneous Vaccine Reactions and Facial Fillers

As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.² The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).^2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.⁴

Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.⁵ A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.⁶ The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.⁷

After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.^2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.⁹ The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.⁹

The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.³

Counseling Patients and Reducing Risks

As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.³

Managing Vaccine Reactions

If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.^3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,⁹ but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.

If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.² In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.

Final Thoughts

As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.

As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.¹ Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.

Cutaneous Vaccine Reactions and Facial Fillers

As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.² The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).^2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.⁴

Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.⁵ A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.⁶ The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.⁷

After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.^2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.⁹ The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.⁹

The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.³

Counseling Patients and Reducing Risks

As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.³

Managing Vaccine Reactions

If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.^3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,⁹ but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.

If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.² In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.

Final Thoughts

As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.

As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.¹ Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.

Cutaneous Vaccine Reactions and Facial Fillers

As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.² The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).^2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.⁴

Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.⁵ A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.⁶ The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.⁷

After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.^2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.⁹ The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.⁹

The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.³

Counseling Patients and Reducing Risks

As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.³

Managing Vaccine Reactions

If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.^3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,⁹ but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.

If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.² In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.

Final Thoughts

As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.

Case Report

A 67-year-old woman presented with a painful expanding ulcer on the left leg and a new nearby ulcer of 2 months’ duration. She initially was seen 2 months prior for a wound on the left knee due to a fall as well as cellulitis, which was treated with intravenous vancomycin and ceftriaxone. Wound cultures were negative for bacteria, and she was discharged without antibiotics. She presented to the emergency department 1 month later for malodorous discharge of the first ulcer with zero systemic inflammatory response syndrome criteria; no fever; and no abnormal heart rate, respiratory rate, or leukocyte count. She was discharged with wound care. After 3 weeks, she returned with a second ulcer and worsening drainage but zero systemic inflammatory response syndrome criteria. She had a medical history of Crohn disease with 9-year remission, atrial fibrillation, pacemaker, mitral valve replacement, chronic obstructive pulmonary disease, and a 51 pack-year smoking history.

Physical examination of the left leg revealed a 3×3-cm deep lesion (ulcer A) on the distal left thigh located superomedial to the knee (Figure 1) as well as a 2×1-cm deep lesion (ulcer B) on the anteromedial knee with undermining and tunneling (Figure 2). A large amount of malodorous tan bloody discharge was present on both ulcers. There were no signs of induration or crepitus.Due to concerns of skin and soft tissue infection (SSTI) or osteomyelitis, a bone scan and wound and blood cultures were ordered. The patient was started on vancomycin and piperacillin-tazobactam in the emergency department, which later was augmented with cefepime. Trauma surgery scheduled debridement for the following morning with suspicion of necrotizing fasciitis. Additional consultations were requested, including infectious disease, wound care, and dermatology. Dermatology evaluated the wound, performed a punch biopsy, and canceled debridement due to unclear diagnosis. The clinical differential at that time included pyoderma gangrenosum (PG), atypical vasculitis, or infection. Additional workup revealed positive antineutrophil cytoplasmic antibodies but negative proteinase 3 and myeloperoxidase, disfavoring vasculitis. Wound cultures grew Staphylococcus aureus and Pseudomonas aeruginosa.

Comment

Pyoderma gangrenosum is a rare inflammatory skin condition that classically presents as tender papules or pustules evolving into painful ulcers, most commonly on the lower extremities. Pyoderma gangrenosum has a propensity to exhibit pathergy, the hyperreactivity of the skin in response to minor trauma. This phenomenon in PG manifests as the rapid evolution from pustule to ulceration with violaceous undermining borders.

Diagnosis of PG
Pyoderma gangrenosum has been described as a diagnosis of exclusion, as its findings frequently mimic SSTIs. Important findings to obtain are histology, history, ulcer morphology, and response to treatment.

In 2018, Maverakis et al¹ proposed diagnostic criteria for classic ulcerative PG (Table 1). A diagnosis of PG can be made if the patient meets 1 major criterion and 4 minor criteria. Our case met 0 major criteria and 5 minor criteria: history of inflammatory bowel disease (IBD); history of pustule ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, with at least 1 on an anterior lower leg; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Although our patient’s biopsy demonstrated a mixed infiltrate, PG was not excluded due to spontaneous resolution at the time of biopsy, emphasizing the need to biopsy subsequent new lesions if neutrophils are not initially seen.¹ Pyoderma gangrenosum frequently is associated with IBD, most often Crohn disease, as seen in our patient.^2-4 Although IBD classically is associated with smoking, studies have yet to conclude if smoking is a predictive factor of PG.⁵ Our patient presented with an initial ulcer that evolved into 2 ulcers, similar to a case of bilateral ulcers.⁶

Management of PG
A gold standard of treatment of PG does not exist, but the goal is to promote wound healing. Patients with limited disease typically can be managed with wound care and topical steroids or calcineurin inhibitors, though data on efficacy are limited. However, our patient had more extensive disease and needed to be treated with systemic therapy. First-line therapy for extensive disease includes oral prednisone or cyclosporine for patients who cannot tolerate systemic corticosteroids.¹² Second-line and adjunctive therapy options include dapsone, minocycline, methotrexate, and infliximab. Our patient was prescribed a 7-month course of dapsone with outpatient dermatology and demonstrated resolution of both ulcers. Dapsone was tapered from a daily dose of 100 mg to 50 mg to 25 mg to none over the course of 2 to 3 months. Close monitoring with wound care is recommended, and petroleum jelly can be used for dry skin around the lesion for comfort.

Conclusion

The diagnosis of PG is challenging because it relies heavily on clinical signs and often mimics SSTI. Gathering a detailed medical history is critical to make the diagnosis of PG. In a patient with associated features of PG, dermatologic consultation and biopsy of skin lesions should be considered. Physicians should evaluate for suspected PG prior to proceeding with surgical intervention to avoid unnecessary amputation. The diagnostic criteria for classic ulcerative PG are gaining wider acceptance and are a useful tool for clinicians.

Case Report

A 67-year-old woman presented with a painful expanding ulcer on the left leg and a new nearby ulcer of 2 months’ duration. She initially was seen 2 months prior for a wound on the left knee due to a fall as well as cellulitis, which was treated with intravenous vancomycin and ceftriaxone. Wound cultures were negative for bacteria, and she was discharged without antibiotics. She presented to the emergency department 1 month later for malodorous discharge of the first ulcer with zero systemic inflammatory response syndrome criteria; no fever; and no abnormal heart rate, respiratory rate, or leukocyte count. She was discharged with wound care. After 3 weeks, she returned with a second ulcer and worsening drainage but zero systemic inflammatory response syndrome criteria. She had a medical history of Crohn disease with 9-year remission, atrial fibrillation, pacemaker, mitral valve replacement, chronic obstructive pulmonary disease, and a 51 pack-year smoking history.

Physical examination of the left leg revealed a 3×3-cm deep lesion (ulcer A) on the distal left thigh located superomedial to the knee (Figure 1) as well as a 2×1-cm deep lesion (ulcer B) on the anteromedial knee with undermining and tunneling (Figure 2). A large amount of malodorous tan bloody discharge was present on both ulcers. There were no signs of induration or crepitus.Due to concerns of skin and soft tissue infection (SSTI) or osteomyelitis, a bone scan and wound and blood cultures were ordered. The patient was started on vancomycin and piperacillin-tazobactam in the emergency department, which later was augmented with cefepime. Trauma surgery scheduled debridement for the following morning with suspicion of necrotizing fasciitis. Additional consultations were requested, including infectious disease, wound care, and dermatology. Dermatology evaluated the wound, performed a punch biopsy, and canceled debridement due to unclear diagnosis. The clinical differential at that time included pyoderma gangrenosum (PG), atypical vasculitis, or infection. Additional workup revealed positive antineutrophil cytoplasmic antibodies but negative proteinase 3 and myeloperoxidase, disfavoring vasculitis. Wound cultures grew Staphylococcus aureus and Pseudomonas aeruginosa.

Comment

Pyoderma gangrenosum is a rare inflammatory skin condition that classically presents as tender papules or pustules evolving into painful ulcers, most commonly on the lower extremities. Pyoderma gangrenosum has a propensity to exhibit pathergy, the hyperreactivity of the skin in response to minor trauma. This phenomenon in PG manifests as the rapid evolution from pustule to ulceration with violaceous undermining borders.

Diagnosis of PG
Pyoderma gangrenosum has been described as a diagnosis of exclusion, as its findings frequently mimic SSTIs. Important findings to obtain are histology, history, ulcer morphology, and response to treatment.

In 2018, Maverakis et al¹ proposed diagnostic criteria for classic ulcerative PG (Table 1). A diagnosis of PG can be made if the patient meets 1 major criterion and 4 minor criteria. Our case met 0 major criteria and 5 minor criteria: history of inflammatory bowel disease (IBD); history of pustule ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, with at least 1 on an anterior lower leg; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Although our patient’s biopsy demonstrated a mixed infiltrate, PG was not excluded due to spontaneous resolution at the time of biopsy, emphasizing the need to biopsy subsequent new lesions if neutrophils are not initially seen.¹ Pyoderma gangrenosum frequently is associated with IBD, most often Crohn disease, as seen in our patient.^2-4 Although IBD classically is associated with smoking, studies have yet to conclude if smoking is a predictive factor of PG.⁵ Our patient presented with an initial ulcer that evolved into 2 ulcers, similar to a case of bilateral ulcers.⁶

Management of PG
A gold standard of treatment of PG does not exist, but the goal is to promote wound healing. Patients with limited disease typically can be managed with wound care and topical steroids or calcineurin inhibitors, though data on efficacy are limited. However, our patient had more extensive disease and needed to be treated with systemic therapy. First-line therapy for extensive disease includes oral prednisone or cyclosporine for patients who cannot tolerate systemic corticosteroids.¹² Second-line and adjunctive therapy options include dapsone, minocycline, methotrexate, and infliximab. Our patient was prescribed a 7-month course of dapsone with outpatient dermatology and demonstrated resolution of both ulcers. Dapsone was tapered from a daily dose of 100 mg to 50 mg to 25 mg to none over the course of 2 to 3 months. Close monitoring with wound care is recommended, and petroleum jelly can be used for dry skin around the lesion for comfort.

Conclusion

The diagnosis of PG is challenging because it relies heavily on clinical signs and often mimics SSTI. Gathering a detailed medical history is critical to make the diagnosis of PG. In a patient with associated features of PG, dermatologic consultation and biopsy of skin lesions should be considered. Physicians should evaluate for suspected PG prior to proceeding with surgical intervention to avoid unnecessary amputation. The diagnostic criteria for classic ulcerative PG are gaining wider acceptance and are a useful tool for clinicians.

Case Report

A 67-year-old woman presented with a painful expanding ulcer on the left leg and a new nearby ulcer of 2 months’ duration. She initially was seen 2 months prior for a wound on the left knee due to a fall as well as cellulitis, which was treated with intravenous vancomycin and ceftriaxone. Wound cultures were negative for bacteria, and she was discharged without antibiotics. She presented to the emergency department 1 month later for malodorous discharge of the first ulcer with zero systemic inflammatory response syndrome criteria; no fever; and no abnormal heart rate, respiratory rate, or leukocyte count. She was discharged with wound care. After 3 weeks, she returned with a second ulcer and worsening drainage but zero systemic inflammatory response syndrome criteria. She had a medical history of Crohn disease with 9-year remission, atrial fibrillation, pacemaker, mitral valve replacement, chronic obstructive pulmonary disease, and a 51 pack-year smoking history.

Physical examination of the left leg revealed a 3×3-cm deep lesion (ulcer A) on the distal left thigh located superomedial to the knee (Figure 1) as well as a 2×1-cm deep lesion (ulcer B) on the anteromedial knee with undermining and tunneling (Figure 2). A large amount of malodorous tan bloody discharge was present on both ulcers. There were no signs of induration or crepitus.Due to concerns of skin and soft tissue infection (SSTI) or osteomyelitis, a bone scan and wound and blood cultures were ordered. The patient was started on vancomycin and piperacillin-tazobactam in the emergency department, which later was augmented with cefepime. Trauma surgery scheduled debridement for the following morning with suspicion of necrotizing fasciitis. Additional consultations were requested, including infectious disease, wound care, and dermatology. Dermatology evaluated the wound, performed a punch biopsy, and canceled debridement due to unclear diagnosis. The clinical differential at that time included pyoderma gangrenosum (PG), atypical vasculitis, or infection. Additional workup revealed positive antineutrophil cytoplasmic antibodies but negative proteinase 3 and myeloperoxidase, disfavoring vasculitis. Wound cultures grew Staphylococcus aureus and Pseudomonas aeruginosa.

Comment

Pyoderma gangrenosum is a rare inflammatory skin condition that classically presents as tender papules or pustules evolving into painful ulcers, most commonly on the lower extremities. Pyoderma gangrenosum has a propensity to exhibit pathergy, the hyperreactivity of the skin in response to minor trauma. This phenomenon in PG manifests as the rapid evolution from pustule to ulceration with violaceous undermining borders.

Diagnosis of PG
Pyoderma gangrenosum has been described as a diagnosis of exclusion, as its findings frequently mimic SSTIs. Important findings to obtain are histology, history, ulcer morphology, and response to treatment.

In 2018, Maverakis et al¹ proposed diagnostic criteria for classic ulcerative PG (Table 1). A diagnosis of PG can be made if the patient meets 1 major criterion and 4 minor criteria. Our case met 0 major criteria and 5 minor criteria: history of inflammatory bowel disease (IBD); history of pustule ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, with at least 1 on an anterior lower leg; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Although our patient’s biopsy demonstrated a mixed infiltrate, PG was not excluded due to spontaneous resolution at the time of biopsy, emphasizing the need to biopsy subsequent new lesions if neutrophils are not initially seen.¹ Pyoderma gangrenosum frequently is associated with IBD, most often Crohn disease, as seen in our patient.^2-4 Although IBD classically is associated with smoking, studies have yet to conclude if smoking is a predictive factor of PG.⁵ Our patient presented with an initial ulcer that evolved into 2 ulcers, similar to a case of bilateral ulcers.⁶

Management of PG
A gold standard of treatment of PG does not exist, but the goal is to promote wound healing. Patients with limited disease typically can be managed with wound care and topical steroids or calcineurin inhibitors, though data on efficacy are limited. However, our patient had more extensive disease and needed to be treated with systemic therapy. First-line therapy for extensive disease includes oral prednisone or cyclosporine for patients who cannot tolerate systemic corticosteroids.¹² Second-line and adjunctive therapy options include dapsone, minocycline, methotrexate, and infliximab. Our patient was prescribed a 7-month course of dapsone with outpatient dermatology and demonstrated resolution of both ulcers. Dapsone was tapered from a daily dose of 100 mg to 50 mg to 25 mg to none over the course of 2 to 3 months. Close monitoring with wound care is recommended, and petroleum jelly can be used for dry skin around the lesion for comfort.

Conclusion

The diagnosis of PG is challenging because it relies heavily on clinical signs and often mimics SSTI. Gathering a detailed medical history is critical to make the diagnosis of PG. In a patient with associated features of PG, dermatologic consultation and biopsy of skin lesions should be considered. Physicians should evaluate for suspected PG prior to proceeding with surgical intervention to avoid unnecessary amputation. The diagnostic criteria for classic ulcerative PG are gaining wider acceptance and are a useful tool for clinicians.

The Diagnosis: Favre-Racouchot Syndrome

Favre-Racouchot syndrome, also known as nodular elastosis with cysts and comedones, is seen in approximately 6% of adults aged 40 to 60 years and predominantly is observed in White males.¹ Typically, patients have a history of prolonged recreational or occupational UV exposure and tobacco use. The diagnosis can be made clinically; no biopsy is necessary. If a biopsy is performed, histologic findings typically consist of notable actinic elastosis, epidermal atrophy, and comedones. The differential diagnosis includes acne comedones, colloid milium, milia, chloracne, and trichoepithelioma.² Associated conditions that have been found concurrently include cutis rhomboidalis nuchae, actinic keratosis, erosive pustular dermatosis, actinic granuloma, and basal and squamous cell carcinomas.²

The pathogenesis, while not fully understood, seems to involve a combination of chronic UV radiation exposure and heavy cigarette smoking that eventually leads to cutaneous atrophy and keratinization of the pilosebaceous follicles as well as the formation of comedones.² Radiation therapy also has been implicated as a possible causative agent of Favre-Racouchot syndrome.¹ Clinically, symmetric distribution of large black comedones over the temporal and periorbital areas is seen surrounded by distinct signs of UV-damaged skin, including wrinkles and atrophic skin.³ Although there seems to be a synergistic effect between cigarette smoking and chronic UV exposure, evidence favors smoking as the major cause of this condition,^4,5 which causes striking visual changes but is a benign process. UV protection and smoking cessation are the most important factors for prevention and limiting progression.

Treatment consists of typical comedonal therapies such as tretinoin or comedone extraction. Procedural options in conjunction with medical therapy include dermabrasion or laser therapy. Newer studies have shown promising results for both CO₂ laser treatment and plasma exeresis.⁶ Plasma exeresis is a noninvasive technique that causes ionization of atmospheric gas between the device and tissue, ultimately causing sublimation of the target tissue.⁷ It is important to carefully evaluate and follow up with these patients due to their history of extensive UV exposure. Both short-term and long-term follow-up is recommended due to high rates of reoccurrence within 10 to 12 months and the dangers of chronic UV exposure– related malignancies.⁶

The Diagnosis: Favre-Racouchot Syndrome

Favre-Racouchot syndrome, also known as nodular elastosis with cysts and comedones, is seen in approximately 6% of adults aged 40 to 60 years and predominantly is observed in White males.¹ Typically, patients have a history of prolonged recreational or occupational UV exposure and tobacco use. The diagnosis can be made clinically; no biopsy is necessary. If a biopsy is performed, histologic findings typically consist of notable actinic elastosis, epidermal atrophy, and comedones. The differential diagnosis includes acne comedones, colloid milium, milia, chloracne, and trichoepithelioma.² Associated conditions that have been found concurrently include cutis rhomboidalis nuchae, actinic keratosis, erosive pustular dermatosis, actinic granuloma, and basal and squamous cell carcinomas.²

The pathogenesis, while not fully understood, seems to involve a combination of chronic UV radiation exposure and heavy cigarette smoking that eventually leads to cutaneous atrophy and keratinization of the pilosebaceous follicles as well as the formation of comedones.² Radiation therapy also has been implicated as a possible causative agent of Favre-Racouchot syndrome.¹ Clinically, symmetric distribution of large black comedones over the temporal and periorbital areas is seen surrounded by distinct signs of UV-damaged skin, including wrinkles and atrophic skin.³ Although there seems to be a synergistic effect between cigarette smoking and chronic UV exposure, evidence favors smoking as the major cause of this condition,^4,5 which causes striking visual changes but is a benign process. UV protection and smoking cessation are the most important factors for prevention and limiting progression.

Treatment consists of typical comedonal therapies such as tretinoin or comedone extraction. Procedural options in conjunction with medical therapy include dermabrasion or laser therapy. Newer studies have shown promising results for both CO₂ laser treatment and plasma exeresis.⁶ Plasma exeresis is a noninvasive technique that causes ionization of atmospheric gas between the device and tissue, ultimately causing sublimation of the target tissue.⁷ It is important to carefully evaluate and follow up with these patients due to their history of extensive UV exposure. Both short-term and long-term follow-up is recommended due to high rates of reoccurrence within 10 to 12 months and the dangers of chronic UV exposure– related malignancies.⁶

The Diagnosis: Favre-Racouchot Syndrome

Favre-Racouchot syndrome, also known as nodular elastosis with cysts and comedones, is seen in approximately 6% of adults aged 40 to 60 years and predominantly is observed in White males.¹ Typically, patients have a history of prolonged recreational or occupational UV exposure and tobacco use. The diagnosis can be made clinically; no biopsy is necessary. If a biopsy is performed, histologic findings typically consist of notable actinic elastosis, epidermal atrophy, and comedones. The differential diagnosis includes acne comedones, colloid milium, milia, chloracne, and trichoepithelioma.² Associated conditions that have been found concurrently include cutis rhomboidalis nuchae, actinic keratosis, erosive pustular dermatosis, actinic granuloma, and basal and squamous cell carcinomas.²

The pathogenesis, while not fully understood, seems to involve a combination of chronic UV radiation exposure and heavy cigarette smoking that eventually leads to cutaneous atrophy and keratinization of the pilosebaceous follicles as well as the formation of comedones.² Radiation therapy also has been implicated as a possible causative agent of Favre-Racouchot syndrome.¹ Clinically, symmetric distribution of large black comedones over the temporal and periorbital areas is seen surrounded by distinct signs of UV-damaged skin, including wrinkles and atrophic skin.³ Although there seems to be a synergistic effect between cigarette smoking and chronic UV exposure, evidence favors smoking as the major cause of this condition,^4,5 which causes striking visual changes but is a benign process. UV protection and smoking cessation are the most important factors for prevention and limiting progression.

Treatment consists of typical comedonal therapies such as tretinoin or comedone extraction. Procedural options in conjunction with medical therapy include dermabrasion or laser therapy. Newer studies have shown promising results for both CO₂ laser treatment and plasma exeresis.⁶ Plasma exeresis is a noninvasive technique that causes ionization of atmospheric gas between the device and tissue, ultimately causing sublimation of the target tissue.⁷ It is important to carefully evaluate and follow up with these patients due to their history of extensive UV exposure. Both short-term and long-term follow-up is recommended due to high rates of reoccurrence within 10 to 12 months and the dangers of chronic UV exposure– related malignancies.⁶

Communication and relationships cannot be taken for granted, particularly in the physician-patient relationship, where life-altering diagnoses may be given. With one diagnosis, someone’s life may be changed, and both physicians and patients need to be cognizant of the importance of a strong relationship and clear communication.

In the current US health care system, both physicians and patients often are not getting their needs met, and studies that include factors of race, ethnicity, and socioeconomic status suggest that physician-patient relationship barriers contribute to racial disparities in health care.^1,2 Although patient-centered care is a widely recognized and upheld model, relationship-centered care between physician and patient involves focusing on the patient and the physician-patient relationship through recognizing personhood, affect (being empathic), and reciprocal influence.^3,4 Although it is not necessarily intuitive because it can appear to be yet another task for busy physicians, relationship-centered care improves health care delivery for both physicians and patients through decreased physician burnout, reduced medical errors, and better patient outcomes and satisfaction.^5,6

Every physician, patient, and physician-patient relationship is different; unlike the standard questions directed at a routine patient history focused on gathering data, there is no one-size-fits-all relationship-centered conversation.^7-10 As with any successful interaction between 2 people, there is a certain amount of necessary self-awareness (Table 1)¹¹ that allows for improvisation and appropriate responsiveness to what is seen, heard, and felt. Rather than attending solely to disease states, the focus of relationship-centered care is on patients, interpersonal interaction, and promoting health and well-being.¹⁵

This review summarizes the existing literature on relationship-centered care, introduces the use of metacognition (Table 1), and suggests creating simple habits to promote such care. The following databases were searched from inception through November 23, 2020, using the term relationship-centered care: MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), Scopus, Web of Science Core Collection, CINAHL Complete (EBSCO), Academic Search Premier (EBSCOhost), and ERIC (ProQuest). A total of 1772 records were retrieved through searches, and after deduplication of 1116 studies, 350 records were screened through a 2-part process. Articles were first screened by title and abstract for relevance to the relationship between physician and patient, with 185 studies deemed irrelevant (eg, pertaining to the relationship of veterinarian to animal). The remaining 165 studies were assessed for eligibility, with 69 further studies excluded for various reasons. The screening process resulted in 96 articles considered in this review.

Definitions/key terms, as used in this article, are listed in Table 1.

Background of Relationship-Centered Care

Given time constraints, the diagnosis and treatment of medical problems often are the focus of physicians. Although proper medical diagnosis and treatment are important, and their delivery is made possible by the physician having the appropriate knowledge, a physician-patient relationship that focuses solely on disease without acknowledging the patient creates a system that ultimately neglects both patients and physicians.¹⁵ This prevailing physician-patient relationship paradigm is suboptimal, and a proposed remedy is relationship-centered care, which focuses on relationships among the human beings in health care interactions.³ Relationship-centered care has 4 principles: (1) the personhood of each party must be recognized, (2) emotion is part of relationships, (3) relationships are reciprocal and not just one way, and (4) creating these types of relationships is morally valuable³ and beneficial to patient care.¹⁶

Assessment of the Need for Relationship-Centered Care

Relationship-centered care has been studied in physician-patient interactions in various health care settings.^17-23 For at least 2 decades, relationship-centered care has been set forth as a model,^4,24,25 but there are challenges. Physicians tend to overrate or underrate their communication skills in patient interactions.^26,27 A given physician’s preferences often still seem to supersede those of the patient.^3,28,29 The impetus to develop relationship-centered care skills generally needs to be internally driven,^4,30 as, ultimately, physicians and patients have varying needs.^4,31 However, providing physicians with a potential structure is helpful.³²

A Solution: Metacognition in the Physician-Patient Interaction

Metacognition is important to integrating basic science knowledge into medical learning and practice,^33,34 and it is no less important in translating interpersonal knowledge to the physician-patient interaction. Decreased metacognitive effort³⁵ may underpin the decline in empathy seen with increasing medical training.^36,37 Understanding how metacognitive practices foster relationship-centered care is important for teaching, developing, and maintaining that care.

Metacognition is already embedded in the fabric of the physician-patient interaction.^33,34 The complex interplay of the physician-patient interview, patient examination, and integration of physical as well as ancillary data requires higher-order thinking and the ability to parse out that thinking successfully. As a concrete example, coming to a diagnosis requires thinking about what has been presented during the physician-patient interaction and considering what supports and suggests the disease while a list of potential differential diagnosis alternatives is being generated. Physicians are trained to apply this clinical reasoning approach to their patient care.

Conversely, although communication skills are a key component of doctoring,³⁸ both between physician and patient as well as among other colleagues and staff, many physicians have never received formal training in communication skills,^26,32,39 though it is now an integral part of medical school curricula.⁴⁰ When such training is mandatory, less than 1% of physicians continue to believe that there was no benefit, even from a single 8-hour communications skills training session.⁴¹ Communication cannot be taught comprehensively in 8 hours; thus, the benefit of such training may be the end result of metacognition and increased self-awareness (Table 1).^42,43

Building Relationship-Centered Care Through Metacognitive Attention

Metacognition as manifested by such self-awareness can build relationship-centered care.⁴ Self-awareness can be taught through mentorship or role models.⁴⁴ Journaling,⁴⁰ meditation, and appreciation of beauty and the arts⁴⁵ can contribute, as well as more formal training programs,^32,38,42 as offered by the Academy of Communication in Healthcare. Creating opportunities for patient empowerment also supports relationship-centered care, as does applying knowledge of implicit bias.⁴⁶

Even without formal training, relationship-centered care can be built through attention to cues⁹—visual (eg, sitting down, other body language),^47,48 auditory (eg, knocking, language, tone, conversational flow),^48,49 and emotional (eg, clinical empathy, emotional intelligence)(Table 2). Such attention is familiar to everyone, not just physicians or patients, through interactions outside of health care; inattention may be due to the hidden curriculum or culture of medicine⁴⁰ as well as real-time changes, such as the introduction of the electronic health record.⁵¹ Inattention to these cues also may be a result of context-specific knowledge, in which a physician’s real-life communication skills are not applied to the unique context of patient care.

Metacognitive Attention Can Generate Habit

Taking metacognition a step further, these small interventions can become habit^11,14,39 through self-awareness, deliberate practice, and feedback.⁴³ Habit is generated by linking a given intervention to another defined cue. For example, placing a hand on a doorknob to enter an examination room can be the cue to generate a habit of entering with presence.¹⁴ Alternatively, before entering an examination room, taking 3 deep breaths can be the cue to trigger presence.¹⁴ Habits can be created in just 3 weeks,⁵⁷ and other proposed cues to generate habits toward relationship-centered care are listed in Table 2. By creating habit through metacognitive attention, relationship-centered care will become something that happens subconsciously without further burdening physicians with another task. Asking patients for permission to record video of an interaction also can create opportunities for self-awareness and self-evaluation through rewatching the video.⁵⁸

Final Thoughts

Physicians already have the tools to create relationship-centered care in physician-patient interactions. A critical mental shift is to develop habits and apply thinking patterns toward understanding and responding appropriately to patients of all ethnicities and their emotions in the physician-patient interaction. This shift is aided by metacognitive awareness (Table 1) and the development of useful habits (Table 2).

Communication and relationships cannot be taken for granted, particularly in the physician-patient relationship, where life-altering diagnoses may be given. With one diagnosis, someone’s life may be changed, and both physicians and patients need to be cognizant of the importance of a strong relationship and clear communication.

In the current US health care system, both physicians and patients often are not getting their needs met, and studies that include factors of race, ethnicity, and socioeconomic status suggest that physician-patient relationship barriers contribute to racial disparities in health care.^1,2 Although patient-centered care is a widely recognized and upheld model, relationship-centered care between physician and patient involves focusing on the patient and the physician-patient relationship through recognizing personhood, affect (being empathic), and reciprocal influence.^3,4 Although it is not necessarily intuitive because it can appear to be yet another task for busy physicians, relationship-centered care improves health care delivery for both physicians and patients through decreased physician burnout, reduced medical errors, and better patient outcomes and satisfaction.^5,6

Every physician, patient, and physician-patient relationship is different; unlike the standard questions directed at a routine patient history focused on gathering data, there is no one-size-fits-all relationship-centered conversation.^7-10 As with any successful interaction between 2 people, there is a certain amount of necessary self-awareness (Table 1)¹¹ that allows for improvisation and appropriate responsiveness to what is seen, heard, and felt. Rather than attending solely to disease states, the focus of relationship-centered care is on patients, interpersonal interaction, and promoting health and well-being.¹⁵

This review summarizes the existing literature on relationship-centered care, introduces the use of metacognition (Table 1), and suggests creating simple habits to promote such care. The following databases were searched from inception through November 23, 2020, using the term relationship-centered care: MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), Scopus, Web of Science Core Collection, CINAHL Complete (EBSCO), Academic Search Premier (EBSCOhost), and ERIC (ProQuest). A total of 1772 records were retrieved through searches, and after deduplication of 1116 studies, 350 records were screened through a 2-part process. Articles were first screened by title and abstract for relevance to the relationship between physician and patient, with 185 studies deemed irrelevant (eg, pertaining to the relationship of veterinarian to animal). The remaining 165 studies were assessed for eligibility, with 69 further studies excluded for various reasons. The screening process resulted in 96 articles considered in this review.

Definitions/key terms, as used in this article, are listed in Table 1.

Background of Relationship-Centered Care

Given time constraints, the diagnosis and treatment of medical problems often are the focus of physicians. Although proper medical diagnosis and treatment are important, and their delivery is made possible by the physician having the appropriate knowledge, a physician-patient relationship that focuses solely on disease without acknowledging the patient creates a system that ultimately neglects both patients and physicians.¹⁵ This prevailing physician-patient relationship paradigm is suboptimal, and a proposed remedy is relationship-centered care, which focuses on relationships among the human beings in health care interactions.³ Relationship-centered care has 4 principles: (1) the personhood of each party must be recognized, (2) emotion is part of relationships, (3) relationships are reciprocal and not just one way, and (4) creating these types of relationships is morally valuable³ and beneficial to patient care.¹⁶

Assessment of the Need for Relationship-Centered Care

Relationship-centered care has been studied in physician-patient interactions in various health care settings.^17-23 For at least 2 decades, relationship-centered care has been set forth as a model,^4,24,25 but there are challenges. Physicians tend to overrate or underrate their communication skills in patient interactions.^26,27 A given physician’s preferences often still seem to supersede those of the patient.^3,28,29 The impetus to develop relationship-centered care skills generally needs to be internally driven,^4,30 as, ultimately, physicians and patients have varying needs.^4,31 However, providing physicians with a potential structure is helpful.³²

A Solution: Metacognition in the Physician-Patient Interaction

Metacognition is important to integrating basic science knowledge into medical learning and practice,^33,34 and it is no less important in translating interpersonal knowledge to the physician-patient interaction. Decreased metacognitive effort³⁵ may underpin the decline in empathy seen with increasing medical training.^36,37 Understanding how metacognitive practices foster relationship-centered care is important for teaching, developing, and maintaining that care.

Metacognition is already embedded in the fabric of the physician-patient interaction.^33,34 The complex interplay of the physician-patient interview, patient examination, and integration of physical as well as ancillary data requires higher-order thinking and the ability to parse out that thinking successfully. As a concrete example, coming to a diagnosis requires thinking about what has been presented during the physician-patient interaction and considering what supports and suggests the disease while a list of potential differential diagnosis alternatives is being generated. Physicians are trained to apply this clinical reasoning approach to their patient care.

Conversely, although communication skills are a key component of doctoring,³⁸ both between physician and patient as well as among other colleagues and staff, many physicians have never received formal training in communication skills,^26,32,39 though it is now an integral part of medical school curricula.⁴⁰ When such training is mandatory, less than 1% of physicians continue to believe that there was no benefit, even from a single 8-hour communications skills training session.⁴¹ Communication cannot be taught comprehensively in 8 hours; thus, the benefit of such training may be the end result of metacognition and increased self-awareness (Table 1).^42,43

Building Relationship-Centered Care Through Metacognitive Attention

Metacognition as manifested by such self-awareness can build relationship-centered care.⁴ Self-awareness can be taught through mentorship or role models.⁴⁴ Journaling,⁴⁰ meditation, and appreciation of beauty and the arts⁴⁵ can contribute, as well as more formal training programs,^32,38,42 as offered by the Academy of Communication in Healthcare. Creating opportunities for patient empowerment also supports relationship-centered care, as does applying knowledge of implicit bias.⁴⁶

Even without formal training, relationship-centered care can be built through attention to cues⁹—visual (eg, sitting down, other body language),^47,48 auditory (eg, knocking, language, tone, conversational flow),^48,49 and emotional (eg, clinical empathy, emotional intelligence)(Table 2). Such attention is familiar to everyone, not just physicians or patients, through interactions outside of health care; inattention may be due to the hidden curriculum or culture of medicine⁴⁰ as well as real-time changes, such as the introduction of the electronic health record.⁵¹ Inattention to these cues also may be a result of context-specific knowledge, in which a physician’s real-life communication skills are not applied to the unique context of patient care.

Metacognitive Attention Can Generate Habit

Taking metacognition a step further, these small interventions can become habit^11,14,39 through self-awareness, deliberate practice, and feedback.⁴³ Habit is generated by linking a given intervention to another defined cue. For example, placing a hand on a doorknob to enter an examination room can be the cue to generate a habit of entering with presence.¹⁴ Alternatively, before entering an examination room, taking 3 deep breaths can be the cue to trigger presence.¹⁴ Habits can be created in just 3 weeks,⁵⁷ and other proposed cues to generate habits toward relationship-centered care are listed in Table 2. By creating habit through metacognitive attention, relationship-centered care will become something that happens subconsciously without further burdening physicians with another task. Asking patients for permission to record video of an interaction also can create opportunities for self-awareness and self-evaluation through rewatching the video.⁵⁸

Final Thoughts

Physicians already have the tools to create relationship-centered care in physician-patient interactions. A critical mental shift is to develop habits and apply thinking patterns toward understanding and responding appropriately to patients of all ethnicities and their emotions in the physician-patient interaction. This shift is aided by metacognitive awareness (Table 1) and the development of useful habits (Table 2).

Communication and relationships cannot be taken for granted, particularly in the physician-patient relationship, where life-altering diagnoses may be given. With one diagnosis, someone’s life may be changed, and both physicians and patients need to be cognizant of the importance of a strong relationship and clear communication.

In the current US health care system, both physicians and patients often are not getting their needs met, and studies that include factors of race, ethnicity, and socioeconomic status suggest that physician-patient relationship barriers contribute to racial disparities in health care.^1,2 Although patient-centered care is a widely recognized and upheld model, relationship-centered care between physician and patient involves focusing on the patient and the physician-patient relationship through recognizing personhood, affect (being empathic), and reciprocal influence.^3,4 Although it is not necessarily intuitive because it can appear to be yet another task for busy physicians, relationship-centered care improves health care delivery for both physicians and patients through decreased physician burnout, reduced medical errors, and better patient outcomes and satisfaction.^5,6

Every physician, patient, and physician-patient relationship is different; unlike the standard questions directed at a routine patient history focused on gathering data, there is no one-size-fits-all relationship-centered conversation.^7-10 As with any successful interaction between 2 people, there is a certain amount of necessary self-awareness (Table 1)¹¹ that allows for improvisation and appropriate responsiveness to what is seen, heard, and felt. Rather than attending solely to disease states, the focus of relationship-centered care is on patients, interpersonal interaction, and promoting health and well-being.¹⁵

This review summarizes the existing literature on relationship-centered care, introduces the use of metacognition (Table 1), and suggests creating simple habits to promote such care. The following databases were searched from inception through November 23, 2020, using the term relationship-centered care: MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), Scopus, Web of Science Core Collection, CINAHL Complete (EBSCO), Academic Search Premier (EBSCOhost), and ERIC (ProQuest). A total of 1772 records were retrieved through searches, and after deduplication of 1116 studies, 350 records were screened through a 2-part process. Articles were first screened by title and abstract for relevance to the relationship between physician and patient, with 185 studies deemed irrelevant (eg, pertaining to the relationship of veterinarian to animal). The remaining 165 studies were assessed for eligibility, with 69 further studies excluded for various reasons. The screening process resulted in 96 articles considered in this review.

Definitions/key terms, as used in this article, are listed in Table 1.

Background of Relationship-Centered Care

Given time constraints, the diagnosis and treatment of medical problems often are the focus of physicians. Although proper medical diagnosis and treatment are important, and their delivery is made possible by the physician having the appropriate knowledge, a physician-patient relationship that focuses solely on disease without acknowledging the patient creates a system that ultimately neglects both patients and physicians.¹⁵ This prevailing physician-patient relationship paradigm is suboptimal, and a proposed remedy is relationship-centered care, which focuses on relationships among the human beings in health care interactions.³ Relationship-centered care has 4 principles: (1) the personhood of each party must be recognized, (2) emotion is part of relationships, (3) relationships are reciprocal and not just one way, and (4) creating these types of relationships is morally valuable³ and beneficial to patient care.¹⁶

Assessment of the Need for Relationship-Centered Care

Relationship-centered care has been studied in physician-patient interactions in various health care settings.^17-23 For at least 2 decades, relationship-centered care has been set forth as a model,^4,24,25 but there are challenges. Physicians tend to overrate or underrate their communication skills in patient interactions.^26,27 A given physician’s preferences often still seem to supersede those of the patient.^3,28,29 The impetus to develop relationship-centered care skills generally needs to be internally driven,^4,30 as, ultimately, physicians and patients have varying needs.^4,31 However, providing physicians with a potential structure is helpful.³²

A Solution: Metacognition in the Physician-Patient Interaction

Metacognition is important to integrating basic science knowledge into medical learning and practice,^33,34 and it is no less important in translating interpersonal knowledge to the physician-patient interaction. Decreased metacognitive effort³⁵ may underpin the decline in empathy seen with increasing medical training.^36,37 Understanding how metacognitive practices foster relationship-centered care is important for teaching, developing, and maintaining that care.

Metacognition is already embedded in the fabric of the physician-patient interaction.^33,34 The complex interplay of the physician-patient interview, patient examination, and integration of physical as well as ancillary data requires higher-order thinking and the ability to parse out that thinking successfully. As a concrete example, coming to a diagnosis requires thinking about what has been presented during the physician-patient interaction and considering what supports and suggests the disease while a list of potential differential diagnosis alternatives is being generated. Physicians are trained to apply this clinical reasoning approach to their patient care.

Conversely, although communication skills are a key component of doctoring,³⁸ both between physician and patient as well as among other colleagues and staff, many physicians have never received formal training in communication skills,^26,32,39 though it is now an integral part of medical school curricula.⁴⁰ When such training is mandatory, less than 1% of physicians continue to believe that there was no benefit, even from a single 8-hour communications skills training session.⁴¹ Communication cannot be taught comprehensively in 8 hours; thus, the benefit of such training may be the end result of metacognition and increased self-awareness (Table 1).^42,43

Building Relationship-Centered Care Through Metacognitive Attention

Metacognition as manifested by such self-awareness can build relationship-centered care.⁴ Self-awareness can be taught through mentorship or role models.⁴⁴ Journaling,⁴⁰ meditation, and appreciation of beauty and the arts⁴⁵ can contribute, as well as more formal training programs,^32,38,42 as offered by the Academy of Communication in Healthcare. Creating opportunities for patient empowerment also supports relationship-centered care, as does applying knowledge of implicit bias.⁴⁶

Even without formal training, relationship-centered care can be built through attention to cues⁹—visual (eg, sitting down, other body language),^47,48 auditory (eg, knocking, language, tone, conversational flow),^48,49 and emotional (eg, clinical empathy, emotional intelligence)(Table 2). Such attention is familiar to everyone, not just physicians or patients, through interactions outside of health care; inattention may be due to the hidden curriculum or culture of medicine⁴⁰ as well as real-time changes, such as the introduction of the electronic health record.⁵¹ Inattention to these cues also may be a result of context-specific knowledge, in which a physician’s real-life communication skills are not applied to the unique context of patient care.

Metacognitive Attention Can Generate Habit

Taking metacognition a step further, these small interventions can become habit^11,14,39 through self-awareness, deliberate practice, and feedback.⁴³ Habit is generated by linking a given intervention to another defined cue. For example, placing a hand on a doorknob to enter an examination room can be the cue to generate a habit of entering with presence.¹⁴ Alternatively, before entering an examination room, taking 3 deep breaths can be the cue to trigger presence.¹⁴ Habits can be created in just 3 weeks,⁵⁷ and other proposed cues to generate habits toward relationship-centered care are listed in Table 2. By creating habit through metacognitive attention, relationship-centered care will become something that happens subconsciously without further burdening physicians with another task. Asking patients for permission to record video of an interaction also can create opportunities for self-awareness and self-evaluation through rewatching the video.⁵⁸

Final Thoughts

Physicians already have the tools to create relationship-centered care in physician-patient interactions. A critical mental shift is to develop habits and apply thinking patterns toward understanding and responding appropriately to patients of all ethnicities and their emotions in the physician-patient interaction. This shift is aided by metacognitive awareness (Table 1) and the development of useful habits (Table 2).

To the Editor:

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome complicated by multiple extracutaneous anomalies, including skeletal defects and neurologic anomalies. Less common associations include lateral curvature of the spine and hyperhidrosis. We present a patient with PPK and unilateral Raynaud phenomenon in addition to a segmental distribution of melanocytic nevi, hyperhidrosis, and scoliosis.

A 9-year-old girl was born with a yellow-orange alopecic plaque on the right side of the scalp (Figure 1). There also were 2 large, irregularly pigmented patches localized on the right side of the upper back and buttock. Over 3 years, numerous papular nevi developed within these pigmented patches and were diagnosed as speckled lentiginous nevi (Figure 2). In addition, numerous nevi of various sizes affected the right face, right shoulder, right arm (Figure 3), and right neck and were clearly demarcated along the midline. Several nevi also were noted within the nevus sebaceous on the right scalp. These skin lesions expanded progressively with age. At 6 years of age, she was diagnosed with hyperhidrosis of the right half of the body, which was most pronounced on the face. Raynaud phenomenon restricted to the right hand also was noted (Figure 4). Upon cold exposure, the digits become pale white, cold, and numb; then blue; and finally red. She lacked other features of connective tissue disease, and autoantibody testing was negative. She also was noted to have an abnormal lateral curvature of the spine (scoliosis). Auditory, ocular, and neurologic examinations were normal. Cranial and cerebral magnetic resonance imaging showed no central nervous system abnormalities. Her family history was negative for nevus spilus, nevus sebaceous, and neurofibromatosis. The clinical findings in our patient led to the diagnosis of PPK.

Raynaud phenomenon involving only the right hand was a unique finding in our patient. In 3 years of follow-up, our patient developed no evidence of connective tissue disease or other systemic illness. We speculate that Raynaud phenomenon of the right hand along with hyperhidrosis of the right side of the body could be a result of dysfunction of the autonomic nervous system. We propose that Raynaud phenomenon represents an unusual manifestation of PPK and may broaden the spectrum of extracutaneous anomalies associated with the disease. The finding of segmental nevi outside of the confines of the nevus spilus was another unusual manifestation of mosaicism.

To the Editor:

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome complicated by multiple extracutaneous anomalies, including skeletal defects and neurologic anomalies. Less common associations include lateral curvature of the spine and hyperhidrosis. We present a patient with PPK and unilateral Raynaud phenomenon in addition to a segmental distribution of melanocytic nevi, hyperhidrosis, and scoliosis.

A 9-year-old girl was born with a yellow-orange alopecic plaque on the right side of the scalp (Figure 1). There also were 2 large, irregularly pigmented patches localized on the right side of the upper back and buttock. Over 3 years, numerous papular nevi developed within these pigmented patches and were diagnosed as speckled lentiginous nevi (Figure 2). In addition, numerous nevi of various sizes affected the right face, right shoulder, right arm (Figure 3), and right neck and were clearly demarcated along the midline. Several nevi also were noted within the nevus sebaceous on the right scalp. These skin lesions expanded progressively with age. At 6 years of age, she was diagnosed with hyperhidrosis of the right half of the body, which was most pronounced on the face. Raynaud phenomenon restricted to the right hand also was noted (Figure 4). Upon cold exposure, the digits become pale white, cold, and numb; then blue; and finally red. She lacked other features of connective tissue disease, and autoantibody testing was negative. She also was noted to have an abnormal lateral curvature of the spine (scoliosis). Auditory, ocular, and neurologic examinations were normal. Cranial and cerebral magnetic resonance imaging showed no central nervous system abnormalities. Her family history was negative for nevus spilus, nevus sebaceous, and neurofibromatosis. The clinical findings in our patient led to the diagnosis of PPK.

Raynaud phenomenon involving only the right hand was a unique finding in our patient. In 3 years of follow-up, our patient developed no evidence of connective tissue disease or other systemic illness. We speculate that Raynaud phenomenon of the right hand along with hyperhidrosis of the right side of the body could be a result of dysfunction of the autonomic nervous system. We propose that Raynaud phenomenon represents an unusual manifestation of PPK and may broaden the spectrum of extracutaneous anomalies associated with the disease. The finding of segmental nevi outside of the confines of the nevus spilus was another unusual manifestation of mosaicism.

To the Editor:

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome complicated by multiple extracutaneous anomalies, including skeletal defects and neurologic anomalies. Less common associations include lateral curvature of the spine and hyperhidrosis. We present a patient with PPK and unilateral Raynaud phenomenon in addition to a segmental distribution of melanocytic nevi, hyperhidrosis, and scoliosis.

A 9-year-old girl was born with a yellow-orange alopecic plaque on the right side of the scalp (Figure 1). There also were 2 large, irregularly pigmented patches localized on the right side of the upper back and buttock. Over 3 years, numerous papular nevi developed within these pigmented patches and were diagnosed as speckled lentiginous nevi (Figure 2). In addition, numerous nevi of various sizes affected the right face, right shoulder, right arm (Figure 3), and right neck and were clearly demarcated along the midline. Several nevi also were noted within the nevus sebaceous on the right scalp. These skin lesions expanded progressively with age. At 6 years of age, she was diagnosed with hyperhidrosis of the right half of the body, which was most pronounced on the face. Raynaud phenomenon restricted to the right hand also was noted (Figure 4). Upon cold exposure, the digits become pale white, cold, and numb; then blue; and finally red. She lacked other features of connective tissue disease, and autoantibody testing was negative. She also was noted to have an abnormal lateral curvature of the spine (scoliosis). Auditory, ocular, and neurologic examinations were normal. Cranial and cerebral magnetic resonance imaging showed no central nervous system abnormalities. Her family history was negative for nevus spilus, nevus sebaceous, and neurofibromatosis. The clinical findings in our patient led to the diagnosis of PPK.

Raynaud phenomenon involving only the right hand was a unique finding in our patient. In 3 years of follow-up, our patient developed no evidence of connective tissue disease or other systemic illness. We speculate that Raynaud phenomenon of the right hand along with hyperhidrosis of the right side of the body could be a result of dysfunction of the autonomic nervous system. We propose that Raynaud phenomenon represents an unusual manifestation of PPK and may broaden the spectrum of extracutaneous anomalies associated with the disease. The finding of segmental nevi outside of the confines of the nevus spilus was another unusual manifestation of mosaicism.

Multidisciplinary tumor boards are composed of providers from many fields who deliver coordinated care for patients with unresectable and high-risk skin cancers. Providers who comprise the tumor board often are radiation oncologists, hematologists/oncologists, general surgeons, dermatologists, dermatologic surgeons, and pathologists. The benefit of having a tumor board is that each patient is evaluated simultaneously by a group of physicians from various specialties who bring diverse perspectives that will contribute to the overall treatment plan. The cases often encompass high-risk tumors including unresectable basal cell carcinomas or invasive melanomas. By combining knowledge from each specialty in a team approach, the tumor board can effectively and holistically develop a care plan for each patient.

For the tumor board at the Warren Alpert Medical School of Brown University (Providence, Rhode Island), we often prepare a presentation with comprehensive details about the patient and tumor. During the presentation, we also propose a treatment plan prior to describing each patient at the weekly conference and amend the plans during the discussion. Tumor boards also provide a consulting role to the community and hospital providers in which patients are being referred by their primary provider and are seeking a second opinion or guidance.

In many ways, the tumor board is a multidisciplinary approach for patient advocacy in the form of treatment. These physicians meet on a regular basis to check on the patient’s progress and continually reevaluate how to have discussions about the patient’s care. There are many reasons why it is important to refer patients to a multidisciplinary tumor board.

Improved Workup and Diagnosis

One of the values of a tumor board is that it allows for patient data to be collected and assembled in a way that tells a story. The specialist from each field can then discuss and weigh the benefits and risks for each diagnostic test that should be performed for the workup in each patient. Physicians who refer their patients to the tumor board use their recommendations to both confirm the diagnosis and shift their treatment plans, depending on the information presented during the meeting.¹ There may be a change in the tumor type, decision to refer for surgery, cancer staging, and list of viable options, especially after reviewing pathology and imaging.² The discussion of the treatment plan may consider not only surgical considerations but also the patient’s quality of life. At times, noninvasive interventions are more appropriate and align with the patient’s goals of care. In addition, during the tumor board clinic there may be new tumors that are identified and biopsied, providing increased diagnosis and surveillance for patients who may have a higher risk for developing skin cancer.

Education for Residents and Providers

The multidisciplinary tumor board not only helps patients but also educates both residents and providers on the evidence-based therapeutic management of high-risk tumors.² Research literature on cutaneous oncology is dynamic, and the weekly tumor board meetings help providers stay informed about the best and most effective treatments for their patients.³ In addition to the attending specialists, participants of the tumor board also may include residents, medical students, medical assistance staff, nurses, physician assistants, and fellows. Furthermore, the recommendations given by the tumor board serve to educate both the patient and the provider who referred them to the tumor board. Although we have access to excellent dermatology textbooks as residents, the most impactful educational experience is seeing the patients in tumor board clinic and participating in the immensely educational discussions at the weekly conferences. Through this experience, I have learned that treatment plans should be personalized to the patient. There are many factors to take into consideration when deciphering what the best course of treatment will be for a patient. Sometimes the best option is Mohs micrographic surgery, while other times it may be scheduling several sessions of palliative radiation oncology. Treatment depends on the individual patient and their condition.

Coordination of Care

During a week that I was on call, I was consulted to biopsy a patient with a giant hemorrhagic basal cell carcinoma that caused substantial cheek and nose distortion as well as anemia secondary to acute blood loss. The patient not only did not have a dermatologist but also did not have a primary care physician given he had not had contact with the health care system in more than 30 years. The reason for him not seeking care was multifactorial, but the approach to his care became multidisciplinary. We sought to connect him with the right providers to help him in any way that we could. We presented him at our multidisciplinary tumor board and started him on sonedigib, a medication that binds to and inhibits the smoothened protein.⁴ Through the tumor board, we were able to establish sustained contact with the patient. The tumor board created effective communication between providers to get him the referrals that he needed for dermatology, pathology, radiation oncology, hematology/oncology, and otolaryngology. The discussions centered around being cognizant of the patient’s apprehension with the health care system as well as providing medical and surgical treatment that would help his quality of life. We built a consensus on what the best plan was for the patient and his family. This consensus would have been more difficult had it not been for the combined specialties of the tumor board. In general, studies have shown that weekly tumor boards have resulted in decreased mortality rates for patients with advanced cancers.⁵

Final Thoughts

The multidisciplinary tumor board is a powerful resource for hospitals and the greater medical community. At these weekly conferences you realize there may still be hope that begins at the line where your expertise ends. It represents a team of providers who compassionately refuse to give up on patients when they are the last refuge.

Multidisciplinary tumor boards are composed of providers from many fields who deliver coordinated care for patients with unresectable and high-risk skin cancers. Providers who comprise the tumor board often are radiation oncologists, hematologists/oncologists, general surgeons, dermatologists, dermatologic surgeons, and pathologists. The benefit of having a tumor board is that each patient is evaluated simultaneously by a group of physicians from various specialties who bring diverse perspectives that will contribute to the overall treatment plan. The cases often encompass high-risk tumors including unresectable basal cell carcinomas or invasive melanomas. By combining knowledge from each specialty in a team approach, the tumor board can effectively and holistically develop a care plan for each patient.

For the tumor board at the Warren Alpert Medical School of Brown University (Providence, Rhode Island), we often prepare a presentation with comprehensive details about the patient and tumor. During the presentation, we also propose a treatment plan prior to describing each patient at the weekly conference and amend the plans during the discussion. Tumor boards also provide a consulting role to the community and hospital providers in which patients are being referred by their primary provider and are seeking a second opinion or guidance.

In many ways, the tumor board is a multidisciplinary approach for patient advocacy in the form of treatment. These physicians meet on a regular basis to check on the patient’s progress and continually reevaluate how to have discussions about the patient’s care. There are many reasons why it is important to refer patients to a multidisciplinary tumor board.

Improved Workup and Diagnosis

One of the values of a tumor board is that it allows for patient data to be collected and assembled in a way that tells a story. The specialist from each field can then discuss and weigh the benefits and risks for each diagnostic test that should be performed for the workup in each patient. Physicians who refer their patients to the tumor board use their recommendations to both confirm the diagnosis and shift their treatment plans, depending on the information presented during the meeting.¹ There may be a change in the tumor type, decision to refer for surgery, cancer staging, and list of viable options, especially after reviewing pathology and imaging.² The discussion of the treatment plan may consider not only surgical considerations but also the patient’s quality of life. At times, noninvasive interventions are more appropriate and align with the patient’s goals of care. In addition, during the tumor board clinic there may be new tumors that are identified and biopsied, providing increased diagnosis and surveillance for patients who may have a higher risk for developing skin cancer.

Education for Residents and Providers

The multidisciplinary tumor board not only helps patients but also educates both residents and providers on the evidence-based therapeutic management of high-risk tumors.² Research literature on cutaneous oncology is dynamic, and the weekly tumor board meetings help providers stay informed about the best and most effective treatments for their patients.³ In addition to the attending specialists, participants of the tumor board also may include residents, medical students, medical assistance staff, nurses, physician assistants, and fellows. Furthermore, the recommendations given by the tumor board serve to educate both the patient and the provider who referred them to the tumor board. Although we have access to excellent dermatology textbooks as residents, the most impactful educational experience is seeing the patients in tumor board clinic and participating in the immensely educational discussions at the weekly conferences. Through this experience, I have learned that treatment plans should be personalized to the patient. There are many factors to take into consideration when deciphering what the best course of treatment will be for a patient. Sometimes the best option is Mohs micrographic surgery, while other times it may be scheduling several sessions of palliative radiation oncology. Treatment depends on the individual patient and their condition.

Coordination of Care

During a week that I was on call, I was consulted to biopsy a patient with a giant hemorrhagic basal cell carcinoma that caused substantial cheek and nose distortion as well as anemia secondary to acute blood loss. The patient not only did not have a dermatologist but also did not have a primary care physician given he had not had contact with the health care system in more than 30 years. The reason for him not seeking care was multifactorial, but the approach to his care became multidisciplinary. We sought to connect him with the right providers to help him in any way that we could. We presented him at our multidisciplinary tumor board and started him on sonedigib, a medication that binds to and inhibits the smoothened protein.⁴ Through the tumor board, we were able to establish sustained contact with the patient. The tumor board created effective communication between providers to get him the referrals that he needed for dermatology, pathology, radiation oncology, hematology/oncology, and otolaryngology. The discussions centered around being cognizant of the patient’s apprehension with the health care system as well as providing medical and surgical treatment that would help his quality of life. We built a consensus on what the best plan was for the patient and his family. This consensus would have been more difficult had it not been for the combined specialties of the tumor board. In general, studies have shown that weekly tumor boards have resulted in decreased mortality rates for patients with advanced cancers.⁵

Final Thoughts

The multidisciplinary tumor board is a powerful resource for hospitals and the greater medical community. At these weekly conferences you realize there may still be hope that begins at the line where your expertise ends. It represents a team of providers who compassionately refuse to give up on patients when they are the last refuge.

Multidisciplinary tumor boards are composed of providers from many fields who deliver coordinated care for patients with unresectable and high-risk skin cancers. Providers who comprise the tumor board often are radiation oncologists, hematologists/oncologists, general surgeons, dermatologists, dermatologic surgeons, and pathologists. The benefit of having a tumor board is that each patient is evaluated simultaneously by a group of physicians from various specialties who bring diverse perspectives that will contribute to the overall treatment plan. The cases often encompass high-risk tumors including unresectable basal cell carcinomas or invasive melanomas. By combining knowledge from each specialty in a team approach, the tumor board can effectively and holistically develop a care plan for each patient.

For the tumor board at the Warren Alpert Medical School of Brown University (Providence, Rhode Island), we often prepare a presentation with comprehensive details about the patient and tumor. During the presentation, we also propose a treatment plan prior to describing each patient at the weekly conference and amend the plans during the discussion. Tumor boards also provide a consulting role to the community and hospital providers in which patients are being referred by their primary provider and are seeking a second opinion or guidance.

In many ways, the tumor board is a multidisciplinary approach for patient advocacy in the form of treatment. These physicians meet on a regular basis to check on the patient’s progress and continually reevaluate how to have discussions about the patient’s care. There are many reasons why it is important to refer patients to a multidisciplinary tumor board.

Improved Workup and Diagnosis

One of the values of a tumor board is that it allows for patient data to be collected and assembled in a way that tells a story. The specialist from each field can then discuss and weigh the benefits and risks for each diagnostic test that should be performed for the workup in each patient. Physicians who refer their patients to the tumor board use their recommendations to both confirm the diagnosis and shift their treatment plans, depending on the information presented during the meeting.¹ There may be a change in the tumor type, decision to refer for surgery, cancer staging, and list of viable options, especially after reviewing pathology and imaging.² The discussion of the treatment plan may consider not only surgical considerations but also the patient’s quality of life. At times, noninvasive interventions are more appropriate and align with the patient’s goals of care. In addition, during the tumor board clinic there may be new tumors that are identified and biopsied, providing increased diagnosis and surveillance for patients who may have a higher risk for developing skin cancer.

Education for Residents and Providers

The multidisciplinary tumor board not only helps patients but also educates both residents and providers on the evidence-based therapeutic management of high-risk tumors.² Research literature on cutaneous oncology is dynamic, and the weekly tumor board meetings help providers stay informed about the best and most effective treatments for their patients.³ In addition to the attending specialists, participants of the tumor board also may include residents, medical students, medical assistance staff, nurses, physician assistants, and fellows. Furthermore, the recommendations given by the tumor board serve to educate both the patient and the provider who referred them to the tumor board. Although we have access to excellent dermatology textbooks as residents, the most impactful educational experience is seeing the patients in tumor board clinic and participating in the immensely educational discussions at the weekly conferences. Through this experience, I have learned that treatment plans should be personalized to the patient. There are many factors to take into consideration when deciphering what the best course of treatment will be for a patient. Sometimes the best option is Mohs micrographic surgery, while other times it may be scheduling several sessions of palliative radiation oncology. Treatment depends on the individual patient and their condition.

Coordination of Care

During a week that I was on call, I was consulted to biopsy a patient with a giant hemorrhagic basal cell carcinoma that caused substantial cheek and nose distortion as well as anemia secondary to acute blood loss. The patient not only did not have a dermatologist but also did not have a primary care physician given he had not had contact with the health care system in more than 30 years. The reason for him not seeking care was multifactorial, but the approach to his care became multidisciplinary. We sought to connect him with the right providers to help him in any way that we could. We presented him at our multidisciplinary tumor board and started him on sonedigib, a medication that binds to and inhibits the smoothened protein.⁴ Through the tumor board, we were able to establish sustained contact with the patient. The tumor board created effective communication between providers to get him the referrals that he needed for dermatology, pathology, radiation oncology, hematology/oncology, and otolaryngology. The discussions centered around being cognizant of the patient’s apprehension with the health care system as well as providing medical and surgical treatment that would help his quality of life. We built a consensus on what the best plan was for the patient and his family. This consensus would have been more difficult had it not been for the combined specialties of the tumor board. In general, studies have shown that weekly tumor boards have resulted in decreased mortality rates for patients with advanced cancers.⁵

Final Thoughts

The multidisciplinary tumor board is a powerful resource for hospitals and the greater medical community. At these weekly conferences you realize there may still be hope that begins at the line where your expertise ends. It represents a team of providers who compassionately refuse to give up on patients when they are the last refuge.