Urticaria

To the Editor:

Urticarial vasculitis (UV) is a clinicopathologic entity. It manifests as an eruption of erythematous wheals that clinically resemble urticaria, but the lesions of UV last longer, may leave residual hyperpigmentation, and may or may not be pruritic.¹ Therapies most often employed include oral antihistamines and systemic immunosuppressant drugs such as corticosteroids, dapsone, colchicine, or hydroxychloroquine.² We present a woman with UV who successfully was treated with omalizumab.

A 49-year-old woman presented to our outpatient clinic with generalized pruritic skin rashes of 2 years’ duration. She also described swelling on the upper eyelids 2 times monthly. She used several antihistamines (up to 4 times daily) and was taking systemic corticosteroids and antidepressants. Physical examination revealed generalized erythematous and edematous papules and plaques on the trunk and extremities (Figure 1). At follow-up a few days later, we observed that the lesions were lasting for more than 24 hours, but there was no residual pigmentation. According to clinical concerns and the association with angioedema, we initially thought the diagnosis was chronic urticaria and angioedema. The patient had no extracutaneous manifestations such as fever, arthralgia, or lymphadenopathy. Routine laboratory examinations including antinuclear antibodies were within reference range. She had normal C3 and C4 levels and an elevated total IgE level (344 IU/mL [reference range, 0–170 IU/mL]). Because the IgE level was elevated and she had no response to the highest dosages of antihistamines, we decided to start omalizumab therapy. Prior to starting omalizumab, we performed a skin biopsy for histopathologic and direct immunofluorescence examinations for UV, as the duration of the lesions was more than 24 hours. Histopathologic examination revealed lymphocytes within the vessel wall and perivascular lymphocytic infiltration with eosinophils (Figure 2). On direct immunofluorescence, perivascular IgA deposition was observed (Figure 3). Histopathologic findings were associated with lymphocytic vasculitis. Systemic involvement was not detected on detailed laboratory and radiologic examinations.

After the first application of omalizumab, the lesions disappeared within a few days. She was treated with subcutaneous omalizumab 300 mg every 4 weeks for 6 months, and we did not observe any adverse effects related to the drug. There was no relapse after therapy cessation.

Omalizumab is a recombinant humanized anti-IgE monoclonal antibody that is approved by the US Food and Drug Administration for treatment of chronic idiopathic urticaria.^3-5 Studies have suggested that omalizumab might play an important role in the treatment of other potentially IgE-mediated disease processes including allergic asthma, atopic dermatitis, allergic rhinitis, nasal polyposis, and severe ocular allergies.⁶ The proposed mechanism of action of omalizumab includes reduction of free IgE through the reversible formation of tiny, biologically inert complexes; targeting IgE-expressing B cells; and inhibiting production of IgE. Because it reduces free IgE, omalizumab has been used in normal IgE or hyper-IgE situations. Omalizumab also induces eosinophil apoptosis; increases IL-2, IL-3, tumor necrosis factor α, and IFN-γ; and reduces IL-4.⁷ A number of off-label uses have been described such as atopic dermatitis, bullous pemphigoid, hyper-IgE syndrome, cutaneous mastocytosis, toxic epidermal necrolysis, and eosinophilic granulomatosis with polyangitis.⁸ There are no clinical studies of omalizumab for UV, and only a few case reports have shown that omalizumab also might be beneficial for this condition.^2-4 Diez et al⁴ reported 3 cases of women aged 28, 51, and 54 years with spontaneous chronic urticaria with autoimmune and pressure components as well as vasculitis whose symptoms completely improved after starting omalizumab. Kai et al³ successfully treated a patient with normocomplementemic UV with omalizumab and suggested that omalizumab markedly improved the patient’s quality of life with chronic urticaria and UV. Ghazanfar and Thomsen² reported the case of a 68-year-old man diagnosed with histopathologically confirmed leukocytoclastic vasculitis. He had used systemic corticosteroid therapy and dapsone without notable improvement. The patient was switched to subcutaneous omalizumab 300 mg once every 4 weeks; after 1 month, he observed complete remission of the UV and symptoms.²

Our case suggests that omalizumab has a beneficial effect on patients with UV. Omalizumab may be effective in UV through its reduction of IgE, as in chronic urticaria, and through downstream effects on cellular activation mechanisms (possibly a reduction in chemotaxis or immune complex formation). However, the mechanism of action of omalizumab for UV remains, in part, unresolved. It is not known whether omalizumab is efficacious against both normocomplementemic and hypocomplementemic UV. Further studies with a greater number of patients are needed to confirm the effects of omalizumab for vasculitic patients.

To the Editor:

Urticarial vasculitis (UV) is a clinicopathologic entity. It manifests as an eruption of erythematous wheals that clinically resemble urticaria, but the lesions of UV last longer, may leave residual hyperpigmentation, and may or may not be pruritic.¹ Therapies most often employed include oral antihistamines and systemic immunosuppressant drugs such as corticosteroids, dapsone, colchicine, or hydroxychloroquine.² We present a woman with UV who successfully was treated with omalizumab.

A 49-year-old woman presented to our outpatient clinic with generalized pruritic skin rashes of 2 years’ duration. She also described swelling on the upper eyelids 2 times monthly. She used several antihistamines (up to 4 times daily) and was taking systemic corticosteroids and antidepressants. Physical examination revealed generalized erythematous and edematous papules and plaques on the trunk and extremities (Figure 1). At follow-up a few days later, we observed that the lesions were lasting for more than 24 hours, but there was no residual pigmentation. According to clinical concerns and the association with angioedema, we initially thought the diagnosis was chronic urticaria and angioedema. The patient had no extracutaneous manifestations such as fever, arthralgia, or lymphadenopathy. Routine laboratory examinations including antinuclear antibodies were within reference range. She had normal C3 and C4 levels and an elevated total IgE level (344 IU/mL [reference range, 0–170 IU/mL]). Because the IgE level was elevated and she had no response to the highest dosages of antihistamines, we decided to start omalizumab therapy. Prior to starting omalizumab, we performed a skin biopsy for histopathologic and direct immunofluorescence examinations for UV, as the duration of the lesions was more than 24 hours. Histopathologic examination revealed lymphocytes within the vessel wall and perivascular lymphocytic infiltration with eosinophils (Figure 2). On direct immunofluorescence, perivascular IgA deposition was observed (Figure 3). Histopathologic findings were associated with lymphocytic vasculitis. Systemic involvement was not detected on detailed laboratory and radiologic examinations.

After the first application of omalizumab, the lesions disappeared within a few days. She was treated with subcutaneous omalizumab 300 mg every 4 weeks for 6 months, and we did not observe any adverse effects related to the drug. There was no relapse after therapy cessation.

Omalizumab is a recombinant humanized anti-IgE monoclonal antibody that is approved by the US Food and Drug Administration for treatment of chronic idiopathic urticaria.^3-5 Studies have suggested that omalizumab might play an important role in the treatment of other potentially IgE-mediated disease processes including allergic asthma, atopic dermatitis, allergic rhinitis, nasal polyposis, and severe ocular allergies.⁶ The proposed mechanism of action of omalizumab includes reduction of free IgE through the reversible formation of tiny, biologically inert complexes; targeting IgE-expressing B cells; and inhibiting production of IgE. Because it reduces free IgE, omalizumab has been used in normal IgE or hyper-IgE situations. Omalizumab also induces eosinophil apoptosis; increases IL-2, IL-3, tumor necrosis factor α, and IFN-γ; and reduces IL-4.⁷ A number of off-label uses have been described such as atopic dermatitis, bullous pemphigoid, hyper-IgE syndrome, cutaneous mastocytosis, toxic epidermal necrolysis, and eosinophilic granulomatosis with polyangitis.⁸ There are no clinical studies of omalizumab for UV, and only a few case reports have shown that omalizumab also might be beneficial for this condition.^2-4 Diez et al⁴ reported 3 cases of women aged 28, 51, and 54 years with spontaneous chronic urticaria with autoimmune and pressure components as well as vasculitis whose symptoms completely improved after starting omalizumab. Kai et al³ successfully treated a patient with normocomplementemic UV with omalizumab and suggested that omalizumab markedly improved the patient’s quality of life with chronic urticaria and UV. Ghazanfar and Thomsen² reported the case of a 68-year-old man diagnosed with histopathologically confirmed leukocytoclastic vasculitis. He had used systemic corticosteroid therapy and dapsone without notable improvement. The patient was switched to subcutaneous omalizumab 300 mg once every 4 weeks; after 1 month, he observed complete remission of the UV and symptoms.²

Our case suggests that omalizumab has a beneficial effect on patients with UV. Omalizumab may be effective in UV through its reduction of IgE, as in chronic urticaria, and through downstream effects on cellular activation mechanisms (possibly a reduction in chemotaxis or immune complex formation). However, the mechanism of action of omalizumab for UV remains, in part, unresolved. It is not known whether omalizumab is efficacious against both normocomplementemic and hypocomplementemic UV. Further studies with a greater number of patients are needed to confirm the effects of omalizumab for vasculitic patients.

To the Editor:

Urticarial vasculitis (UV) is a clinicopathologic entity. It manifests as an eruption of erythematous wheals that clinically resemble urticaria, but the lesions of UV last longer, may leave residual hyperpigmentation, and may or may not be pruritic.¹ Therapies most often employed include oral antihistamines and systemic immunosuppressant drugs such as corticosteroids, dapsone, colchicine, or hydroxychloroquine.² We present a woman with UV who successfully was treated with omalizumab.

A 49-year-old woman presented to our outpatient clinic with generalized pruritic skin rashes of 2 years’ duration. She also described swelling on the upper eyelids 2 times monthly. She used several antihistamines (up to 4 times daily) and was taking systemic corticosteroids and antidepressants. Physical examination revealed generalized erythematous and edematous papules and plaques on the trunk and extremities (Figure 1). At follow-up a few days later, we observed that the lesions were lasting for more than 24 hours, but there was no residual pigmentation. According to clinical concerns and the association with angioedema, we initially thought the diagnosis was chronic urticaria and angioedema. The patient had no extracutaneous manifestations such as fever, arthralgia, or lymphadenopathy. Routine laboratory examinations including antinuclear antibodies were within reference range. She had normal C3 and C4 levels and an elevated total IgE level (344 IU/mL [reference range, 0–170 IU/mL]). Because the IgE level was elevated and she had no response to the highest dosages of antihistamines, we decided to start omalizumab therapy. Prior to starting omalizumab, we performed a skin biopsy for histopathologic and direct immunofluorescence examinations for UV, as the duration of the lesions was more than 24 hours. Histopathologic examination revealed lymphocytes within the vessel wall and perivascular lymphocytic infiltration with eosinophils (Figure 2). On direct immunofluorescence, perivascular IgA deposition was observed (Figure 3). Histopathologic findings were associated with lymphocytic vasculitis. Systemic involvement was not detected on detailed laboratory and radiologic examinations.

After the first application of omalizumab, the lesions disappeared within a few days. She was treated with subcutaneous omalizumab 300 mg every 4 weeks for 6 months, and we did not observe any adverse effects related to the drug. There was no relapse after therapy cessation.

Omalizumab is a recombinant humanized anti-IgE monoclonal antibody that is approved by the US Food and Drug Administration for treatment of chronic idiopathic urticaria.^3-5 Studies have suggested that omalizumab might play an important role in the treatment of other potentially IgE-mediated disease processes including allergic asthma, atopic dermatitis, allergic rhinitis, nasal polyposis, and severe ocular allergies.⁶ The proposed mechanism of action of omalizumab includes reduction of free IgE through the reversible formation of tiny, biologically inert complexes; targeting IgE-expressing B cells; and inhibiting production of IgE. Because it reduces free IgE, omalizumab has been used in normal IgE or hyper-IgE situations. Omalizumab also induces eosinophil apoptosis; increases IL-2, IL-3, tumor necrosis factor α, and IFN-γ; and reduces IL-4.⁷ A number of off-label uses have been described such as atopic dermatitis, bullous pemphigoid, hyper-IgE syndrome, cutaneous mastocytosis, toxic epidermal necrolysis, and eosinophilic granulomatosis with polyangitis.⁸ There are no clinical studies of omalizumab for UV, and only a few case reports have shown that omalizumab also might be beneficial for this condition.^2-4 Diez et al⁴ reported 3 cases of women aged 28, 51, and 54 years with spontaneous chronic urticaria with autoimmune and pressure components as well as vasculitis whose symptoms completely improved after starting omalizumab. Kai et al³ successfully treated a patient with normocomplementemic UV with omalizumab and suggested that omalizumab markedly improved the patient’s quality of life with chronic urticaria and UV. Ghazanfar and Thomsen² reported the case of a 68-year-old man diagnosed with histopathologically confirmed leukocytoclastic vasculitis. He had used systemic corticosteroid therapy and dapsone without notable improvement. The patient was switched to subcutaneous omalizumab 300 mg once every 4 weeks; after 1 month, he observed complete remission of the UV and symptoms.²

Our case suggests that omalizumab has a beneficial effect on patients with UV. Omalizumab may be effective in UV through its reduction of IgE, as in chronic urticaria, and through downstream effects on cellular activation mechanisms (possibly a reduction in chemotaxis or immune complex formation). However, the mechanism of action of omalizumab for UV remains, in part, unresolved. It is not known whether omalizumab is efficacious against both normocomplementemic and hypocomplementemic UV. Further studies with a greater number of patients are needed to confirm the effects of omalizumab for vasculitic patients.

The rate of hospital admissions in the United Kingdom for food-induced anaphylaxis more than tripled over the 20 years from 1998 to 2018, but the case fatality rate fell by more than half, researchers report in BMJ.

“Cow’s milk is increasingly identified as the culprit allergen for fatal food reactions and is now the commonest cause of fatal anaphylaxis in children,” write Alessia Baseggio Conrado, PhD, a biochemist with the National Heart and Lung Institute at Imperial College London, and colleagues. “More education is needed to highlight the specific risks posed by cow’s milk to people who are allergic to increase awareness among food businesses.”

Whereas recognition of the risks posed by nut allergies has increased, people think milk allergy is mild, says senior author Paul. J. Turner, BMBCh, PhD, an allergist/immunologist at Imperial College. “This is often true in very young children, but school-aged children who still have milk allergy tend to have a more allergic profile, often with other allergies, including asthma,” Dr. Turner told this news organization. “Also, milk is very common in our diet, and you don’t need much milk to achieve a decent dose of allergen.”

During the study period, 101,891 people were hospitalized for anaphylaxis; 30,700 cases (30%) were coded as having been triggered by food.

These food-related admissions represent an increase from 1.23 to 4.04 per 100,000 population per year, for an annual increase of 5.7% (95% confidence interval, 5.5-5.9; P < .001), the authors write.

The largest jump occurred among children younger than 15 years, for whom admissions rose from 2.1 to 9.2 per 100,000 population per year, an annual increase of 6.6% (95% CI, 6.3-7.0). The annual increases were 5.9% (95% CI, 5.6-6.2) among persons aged 15 to 59 years and 2.1% (95% CI, 1.8-3.1) among those aged 60 years and older.

The investigators used data from England, Scotland, Wales, and Northern Ireland to track temporal trends and age and sex distributions for hospital admissions for which the primary diagnosis was anaphylaxis attributable to both food and nonfood triggers. These data were compared with nationally reported fatalities.

Over the 20-year period, 152 deaths were attributed to likely food-induced anaphylaxis. During that time, the case fatality rate for confirmed fatal food anaphylaxis fell from 0.7% to 0.19% (rate ratio, 0.931; 95% CI, 0.904-0.959; P < .001) and declined to 0.30% for suspected fatal food anaphylaxis (rate ratio, 0.970; 95% CI, 0.945-0.996; P = .024).

Between 1992 and 2018, at least 46% of all anaphylactic fatalities were deemed to be triggered by peanut or tree nut. Among school-aged children, 26% of anaphylactic fatalities were attributed to cow’s milk.

Not surprisingly, during the study period, there was an increase of 336% in prescriptions for adrenaline autoinjectors. Such prescriptions increased 11% per year.

Global trend

The data extend findings Dr. Turner and colleagues reported for England and Wales in 2014 regarding the entire United Kingdom population and align with epidemiologic trends in hospital admissions for anaphylaxis in the United States and Australia.

The researchers say better recognition and management of anaphylaxis could partly explain the decrease in fatalities, but the rise in hospitalizations remains puzzling. “Whether a true increase in the prevalence of anaphylaxis has occurred (rather than a reduction in the threshold to admit patients presenting with anaphylaxis) is unclear because evidence is lacking for an increase in prevalence of food allergy in the [United Kingdom] (and elsewhere) over the same time period,” they write.

Ronna L. Campbell, MD, PhD, an emergency physician at the Mayo Clinic in Rochester, Minn., has noted similar trends in the United States. “It may be that anaphylaxis recognition and diagnosis have improved, resulting in earlier administration of epinephrine,” Dr. Campbell said in an interview. “So while cases are increasing, earlier recognition and treatment result in decreased fatalities.” She is unaware of any new guidelines recommending increased hospitalization that would explain the puzzling rise in admissions.

According to the study authors, the clinical criteria used to diagnose anaphylaxis in the United Kingdom did not change during the study period. Although national guidance recommending the hospitalization of children younger than 16 who are suspected of having anaphylaxis was introduced in 2011 and may have boosted admissions, the year-on-year rate of increase has persisted since 2014. “Therefore the increase over the past 5 years cannot be attributed to the impact of the guidance,” they write.

The study was funded by grants from the U.K. Medical Research Council and U.K. Food Standards Agency. Two coauthors have disclosed financial relationships with industry outside of the submitted work. Dr. Conrado has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com

The rate of hospital admissions in the United Kingdom for food-induced anaphylaxis more than tripled over the 20 years from 1998 to 2018, but the case fatality rate fell by more than half, researchers report in BMJ.

“Cow’s milk is increasingly identified as the culprit allergen for fatal food reactions and is now the commonest cause of fatal anaphylaxis in children,” write Alessia Baseggio Conrado, PhD, a biochemist with the National Heart and Lung Institute at Imperial College London, and colleagues. “More education is needed to highlight the specific risks posed by cow’s milk to people who are allergic to increase awareness among food businesses.”

Whereas recognition of the risks posed by nut allergies has increased, people think milk allergy is mild, says senior author Paul. J. Turner, BMBCh, PhD, an allergist/immunologist at Imperial College. “This is often true in very young children, but school-aged children who still have milk allergy tend to have a more allergic profile, often with other allergies, including asthma,” Dr. Turner told this news organization. “Also, milk is very common in our diet, and you don’t need much milk to achieve a decent dose of allergen.”

During the study period, 101,891 people were hospitalized for anaphylaxis; 30,700 cases (30%) were coded as having been triggered by food.

These food-related admissions represent an increase from 1.23 to 4.04 per 100,000 population per year, for an annual increase of 5.7% (95% confidence interval, 5.5-5.9; P < .001), the authors write.

The largest jump occurred among children younger than 15 years, for whom admissions rose from 2.1 to 9.2 per 100,000 population per year, an annual increase of 6.6% (95% CI, 6.3-7.0). The annual increases were 5.9% (95% CI, 5.6-6.2) among persons aged 15 to 59 years and 2.1% (95% CI, 1.8-3.1) among those aged 60 years and older.

The investigators used data from England, Scotland, Wales, and Northern Ireland to track temporal trends and age and sex distributions for hospital admissions for which the primary diagnosis was anaphylaxis attributable to both food and nonfood triggers. These data were compared with nationally reported fatalities.

Over the 20-year period, 152 deaths were attributed to likely food-induced anaphylaxis. During that time, the case fatality rate for confirmed fatal food anaphylaxis fell from 0.7% to 0.19% (rate ratio, 0.931; 95% CI, 0.904-0.959; P < .001) and declined to 0.30% for suspected fatal food anaphylaxis (rate ratio, 0.970; 95% CI, 0.945-0.996; P = .024).

Between 1992 and 2018, at least 46% of all anaphylactic fatalities were deemed to be triggered by peanut or tree nut. Among school-aged children, 26% of anaphylactic fatalities were attributed to cow’s milk.

Not surprisingly, during the study period, there was an increase of 336% in prescriptions for adrenaline autoinjectors. Such prescriptions increased 11% per year.

Global trend

The data extend findings Dr. Turner and colleagues reported for England and Wales in 2014 regarding the entire United Kingdom population and align with epidemiologic trends in hospital admissions for anaphylaxis in the United States and Australia.

The researchers say better recognition and management of anaphylaxis could partly explain the decrease in fatalities, but the rise in hospitalizations remains puzzling. “Whether a true increase in the prevalence of anaphylaxis has occurred (rather than a reduction in the threshold to admit patients presenting with anaphylaxis) is unclear because evidence is lacking for an increase in prevalence of food allergy in the [United Kingdom] (and elsewhere) over the same time period,” they write.

Ronna L. Campbell, MD, PhD, an emergency physician at the Mayo Clinic in Rochester, Minn., has noted similar trends in the United States. “It may be that anaphylaxis recognition and diagnosis have improved, resulting in earlier administration of epinephrine,” Dr. Campbell said in an interview. “So while cases are increasing, earlier recognition and treatment result in decreased fatalities.” She is unaware of any new guidelines recommending increased hospitalization that would explain the puzzling rise in admissions.

According to the study authors, the clinical criteria used to diagnose anaphylaxis in the United Kingdom did not change during the study period. Although national guidance recommending the hospitalization of children younger than 16 who are suspected of having anaphylaxis was introduced in 2011 and may have boosted admissions, the year-on-year rate of increase has persisted since 2014. “Therefore the increase over the past 5 years cannot be attributed to the impact of the guidance,” they write.

The study was funded by grants from the U.K. Medical Research Council and U.K. Food Standards Agency. Two coauthors have disclosed financial relationships with industry outside of the submitted work. Dr. Conrado has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com

The rate of hospital admissions in the United Kingdom for food-induced anaphylaxis more than tripled over the 20 years from 1998 to 2018, but the case fatality rate fell by more than half, researchers report in BMJ.

“Cow’s milk is increasingly identified as the culprit allergen for fatal food reactions and is now the commonest cause of fatal anaphylaxis in children,” write Alessia Baseggio Conrado, PhD, a biochemist with the National Heart and Lung Institute at Imperial College London, and colleagues. “More education is needed to highlight the specific risks posed by cow’s milk to people who are allergic to increase awareness among food businesses.”

Whereas recognition of the risks posed by nut allergies has increased, people think milk allergy is mild, says senior author Paul. J. Turner, BMBCh, PhD, an allergist/immunologist at Imperial College. “This is often true in very young children, but school-aged children who still have milk allergy tend to have a more allergic profile, often with other allergies, including asthma,” Dr. Turner told this news organization. “Also, milk is very common in our diet, and you don’t need much milk to achieve a decent dose of allergen.”

During the study period, 101,891 people were hospitalized for anaphylaxis; 30,700 cases (30%) were coded as having been triggered by food.

These food-related admissions represent an increase from 1.23 to 4.04 per 100,000 population per year, for an annual increase of 5.7% (95% confidence interval, 5.5-5.9; P < .001), the authors write.

The largest jump occurred among children younger than 15 years, for whom admissions rose from 2.1 to 9.2 per 100,000 population per year, an annual increase of 6.6% (95% CI, 6.3-7.0). The annual increases were 5.9% (95% CI, 5.6-6.2) among persons aged 15 to 59 years and 2.1% (95% CI, 1.8-3.1) among those aged 60 years and older.

The investigators used data from England, Scotland, Wales, and Northern Ireland to track temporal trends and age and sex distributions for hospital admissions for which the primary diagnosis was anaphylaxis attributable to both food and nonfood triggers. These data were compared with nationally reported fatalities.

Over the 20-year period, 152 deaths were attributed to likely food-induced anaphylaxis. During that time, the case fatality rate for confirmed fatal food anaphylaxis fell from 0.7% to 0.19% (rate ratio, 0.931; 95% CI, 0.904-0.959; P < .001) and declined to 0.30% for suspected fatal food anaphylaxis (rate ratio, 0.970; 95% CI, 0.945-0.996; P = .024).

Between 1992 and 2018, at least 46% of all anaphylactic fatalities were deemed to be triggered by peanut or tree nut. Among school-aged children, 26% of anaphylactic fatalities were attributed to cow’s milk.

Not surprisingly, during the study period, there was an increase of 336% in prescriptions for adrenaline autoinjectors. Such prescriptions increased 11% per year.

Global trend

The data extend findings Dr. Turner and colleagues reported for England and Wales in 2014 regarding the entire United Kingdom population and align with epidemiologic trends in hospital admissions for anaphylaxis in the United States and Australia.

The researchers say better recognition and management of anaphylaxis could partly explain the decrease in fatalities, but the rise in hospitalizations remains puzzling. “Whether a true increase in the prevalence of anaphylaxis has occurred (rather than a reduction in the threshold to admit patients presenting with anaphylaxis) is unclear because evidence is lacking for an increase in prevalence of food allergy in the [United Kingdom] (and elsewhere) over the same time period,” they write.

Ronna L. Campbell, MD, PhD, an emergency physician at the Mayo Clinic in Rochester, Minn., has noted similar trends in the United States. “It may be that anaphylaxis recognition and diagnosis have improved, resulting in earlier administration of epinephrine,” Dr. Campbell said in an interview. “So while cases are increasing, earlier recognition and treatment result in decreased fatalities.” She is unaware of any new guidelines recommending increased hospitalization that would explain the puzzling rise in admissions.

According to the study authors, the clinical criteria used to diagnose anaphylaxis in the United Kingdom did not change during the study period. Although national guidance recommending the hospitalization of children younger than 16 who are suspected of having anaphylaxis was introduced in 2011 and may have boosted admissions, the year-on-year rate of increase has persisted since 2014. “Therefore the increase over the past 5 years cannot be attributed to the impact of the guidance,” they write.

The study was funded by grants from the U.K. Medical Research Council and U.K. Food Standards Agency. Two coauthors have disclosed financial relationships with industry outside of the submitted work. Dr. Conrado has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com

Oral difelikefalin significantly reduced the intense itching associated with stage 3-5 chronic kidney disease, with or without hemodialysis, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.

“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.

Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.

Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.

Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.

The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.

“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.

The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.

A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.

A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.

Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.

Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.

Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).

In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.

“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”

The oral difelikefalin phase 3 program is scheduled to start later in 2020.

CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.

Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.

[email protected]

Oral difelikefalin significantly reduced the intense itching associated with stage 3-5 chronic kidney disease, with or without hemodialysis, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.

“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.

Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.

Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.

Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.

The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.

“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.

The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.

A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.

A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.

Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.

Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.

Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).

In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.

“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”

The oral difelikefalin phase 3 program is scheduled to start later in 2020.

CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.

Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.

[email protected]

Oral difelikefalin significantly reduced the intense itching associated with stage 3-5 chronic kidney disease, with or without hemodialysis, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.

“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.

Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.

Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.

Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.

The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.

“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.

The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.

A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.

A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.

Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.

Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.

Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).

In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.

“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”

The oral difelikefalin phase 3 program is scheduled to start later in 2020.

CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.

Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.

[email protected]

To the Editor:

Raynaud phenomenon is characterized by vasospasm of arterioles causing intermittent ischemia of the digits. The characteristic triphasic color change presents first as a dramatic change in skin color from normal to white, as the vasoconstriction causes pallor secondary to ischemia. This change is followed by a blue appearance, as cyanosis results from the deoxygenated venous blood. Finally, reflex vasodilation and reperfusion manifest as a red color from erythema. Several cases have been reported describing Raynaud phenomenon affecting the nipples of breastfeeding women.^1-5 This vasospasm results in episodic nipple pain manifesting from breastfeeding and exposure to cold. If it is not appropriately treated, the pain’s severity causes affected women to stop breastfeeding. We report a case of vasospasm of the nipple in which the patient experienced nipple pain and a separate lancinating pain that radiated through the breasts.

A 36-year-old woman presented with excruciating nipple and breast pain 3 weeks after delivering her first child. She had no history of smoking or Raynaud phenomenon. The nipple pain was triggered upon breastfeeding and exposure to cold. During these episodes, the nipples would initially blanch white, then turn purple and finally a deep red. The patient also experienced an episodic excruciating lancinating pain of the breast that would randomly and spontaneously radiate through either breast several times per day for 15 to 30 seconds. A workup including an antinuclear antibody test, complete blood cell count with differential, and comprehensive metabolic panel all were within reference range.

The patient was diagnosed with nipple vasospasm. Partial relief of nipple pain occurred after treatment with 30 mg daily of nifedipine; 60 mg daily resulted in complete control, allowing the patient to breastfeed without discomfort, but the lancinating pain continued unabated. The patient could not discontinue breastfeeding because her child was intolerant to formula. She became despondent, as she could find no relief from the pain that she found to be intolerable. Because the patient’s description was reminiscent of the lancinating pain seen in postherpetic neuralgia, a trial of pregabalin was prescribed. A dosage of 75 mg twice daily resulted in near-complete resolution of the pain. After 3 months, the patient successfully weaned her child from breast milk to formula, and the nipple and breast pain promptly resolved. The baby experienced no adverse effects from the patient’s use of pregabalin.

This condition was first described by Gunther¹ in 1970 as initial blanching of the nipple followed by a mulberry color. It was termed psychosomatic sore nipples.¹ Lawlor-Smith and Lawlor-Smith² described the condition in 1997 and termed it vasospasm of the nipple. They reported 5 patients who experienced debilitating nipple pain as well as the triphasic color change of Raynaud phenomenon or a biphasic color change (white and blue). Two patients had a history of Raynaud phenomenon affecting the digits before their first pregnancy.² Anderson et al³ presented 12 breastfeeding women with Raynaud phenomenon of the nipple; only 1 patient had a history of Raynaud phenomenon. In this series, all 6 women who chose to try nifedipine responded well to the drug.³ 

Raynaud phenomenon of the nipple also has been reported to be associated with the use of labetalol.⁴ In this case, the patient had a history of Raynaud phenomenon affecting the toes and nipples on cold days. In 2 subsequent pregnancies she was treated with labetalol for pregnancy-induced hypertension, which resulted in severe nipple pain with each pregnancy unrelated to cold weather. Unlike other cases, this patient experienced antenatal symptoms in addition to the typical postnatal symptoms. The nipple pain resolved with discontinuation of the labetalol.⁴

Barrett et al⁵ conducted a retrospective review of medical records of 88 breastfeeding mothers who presented with nipple pain and dermatitis. They defined the criteria for Raynaud phenomenon of the nipple as chronic deep breast pain (in general lasting >4 weeks) that responded to therapy for the condition and had at least 2 of the following characteristics: (1) observed or self-reported color changes of the nipple, especially with cold exposure (white, blue, or red); (2) cold sensitivity or color changes of the hands or feet with cold exposure; or (3) failed therapy with oral antifungals. Using these criteria, they diagnosed 22 women (25%) with Raynaud phenomenon of the nipple; 20 (91%) reported a history of cold sensitivity or color change of acral surfaces. Of 12 patients who received and tolerated nifedipine use, 10 (83%) reported decreased pain or complete resolution. This series described breast or nipple pain, whereas other reported cases only described nipple pain. The authors described a sharp, shooting, or stabbing pain—qualifications not previously noted.⁵ Our patient experienced both nipple pain and a lancinating breast pain consistent with the cases reported by Barrett et al.⁵

The nipple pain and treatment response in our patient was typical of previously reported cases of vasospasm of the nipple in breastfeeding women; however, Barrett et al⁵ did not describe individual patients who exhibited the dual nature of the pain described in our patient. The nipple pain experienced during breastfeeding in our patient was successfully treated with nifedipine. We report the successful treatment of the separate lancinating pain with pregabalin.

To the Editor:

Raynaud phenomenon is characterized by vasospasm of arterioles causing intermittent ischemia of the digits. The characteristic triphasic color change presents first as a dramatic change in skin color from normal to white, as the vasoconstriction causes pallor secondary to ischemia. This change is followed by a blue appearance, as cyanosis results from the deoxygenated venous blood. Finally, reflex vasodilation and reperfusion manifest as a red color from erythema. Several cases have been reported describing Raynaud phenomenon affecting the nipples of breastfeeding women.^1-5 This vasospasm results in episodic nipple pain manifesting from breastfeeding and exposure to cold. If it is not appropriately treated, the pain’s severity causes affected women to stop breastfeeding. We report a case of vasospasm of the nipple in which the patient experienced nipple pain and a separate lancinating pain that radiated through the breasts.

A 36-year-old woman presented with excruciating nipple and breast pain 3 weeks after delivering her first child. She had no history of smoking or Raynaud phenomenon. The nipple pain was triggered upon breastfeeding and exposure to cold. During these episodes, the nipples would initially blanch white, then turn purple and finally a deep red. The patient also experienced an episodic excruciating lancinating pain of the breast that would randomly and spontaneously radiate through either breast several times per day for 15 to 30 seconds. A workup including an antinuclear antibody test, complete blood cell count with differential, and comprehensive metabolic panel all were within reference range.

The patient was diagnosed with nipple vasospasm. Partial relief of nipple pain occurred after treatment with 30 mg daily of nifedipine; 60 mg daily resulted in complete control, allowing the patient to breastfeed without discomfort, but the lancinating pain continued unabated. The patient could not discontinue breastfeeding because her child was intolerant to formula. She became despondent, as she could find no relief from the pain that she found to be intolerable. Because the patient’s description was reminiscent of the lancinating pain seen in postherpetic neuralgia, a trial of pregabalin was prescribed. A dosage of 75 mg twice daily resulted in near-complete resolution of the pain. After 3 months, the patient successfully weaned her child from breast milk to formula, and the nipple and breast pain promptly resolved. The baby experienced no adverse effects from the patient’s use of pregabalin.

This condition was first described by Gunther¹ in 1970 as initial blanching of the nipple followed by a mulberry color. It was termed psychosomatic sore nipples.¹ Lawlor-Smith and Lawlor-Smith² described the condition in 1997 and termed it vasospasm of the nipple. They reported 5 patients who experienced debilitating nipple pain as well as the triphasic color change of Raynaud phenomenon or a biphasic color change (white and blue). Two patients had a history of Raynaud phenomenon affecting the digits before their first pregnancy.² Anderson et al³ presented 12 breastfeeding women with Raynaud phenomenon of the nipple; only 1 patient had a history of Raynaud phenomenon. In this series, all 6 women who chose to try nifedipine responded well to the drug.³ 

Raynaud phenomenon of the nipple also has been reported to be associated with the use of labetalol.⁴ In this case, the patient had a history of Raynaud phenomenon affecting the toes and nipples on cold days. In 2 subsequent pregnancies she was treated with labetalol for pregnancy-induced hypertension, which resulted in severe nipple pain with each pregnancy unrelated to cold weather. Unlike other cases, this patient experienced antenatal symptoms in addition to the typical postnatal symptoms. The nipple pain resolved with discontinuation of the labetalol.⁴

Barrett et al⁵ conducted a retrospective review of medical records of 88 breastfeeding mothers who presented with nipple pain and dermatitis. They defined the criteria for Raynaud phenomenon of the nipple as chronic deep breast pain (in general lasting >4 weeks) that responded to therapy for the condition and had at least 2 of the following characteristics: (1) observed or self-reported color changes of the nipple, especially with cold exposure (white, blue, or red); (2) cold sensitivity or color changes of the hands or feet with cold exposure; or (3) failed therapy with oral antifungals. Using these criteria, they diagnosed 22 women (25%) with Raynaud phenomenon of the nipple; 20 (91%) reported a history of cold sensitivity or color change of acral surfaces. Of 12 patients who received and tolerated nifedipine use, 10 (83%) reported decreased pain or complete resolution. This series described breast or nipple pain, whereas other reported cases only described nipple pain. The authors described a sharp, shooting, or stabbing pain—qualifications not previously noted.⁵ Our patient experienced both nipple pain and a lancinating breast pain consistent with the cases reported by Barrett et al.⁵

The nipple pain and treatment response in our patient was typical of previously reported cases of vasospasm of the nipple in breastfeeding women; however, Barrett et al⁵ did not describe individual patients who exhibited the dual nature of the pain described in our patient. The nipple pain experienced during breastfeeding in our patient was successfully treated with nifedipine. We report the successful treatment of the separate lancinating pain with pregabalin.

To the Editor:

Raynaud phenomenon is characterized by vasospasm of arterioles causing intermittent ischemia of the digits. The characteristic triphasic color change presents first as a dramatic change in skin color from normal to white, as the vasoconstriction causes pallor secondary to ischemia. This change is followed by a blue appearance, as cyanosis results from the deoxygenated venous blood. Finally, reflex vasodilation and reperfusion manifest as a red color from erythema. Several cases have been reported describing Raynaud phenomenon affecting the nipples of breastfeeding women.^1-5 This vasospasm results in episodic nipple pain manifesting from breastfeeding and exposure to cold. If it is not appropriately treated, the pain’s severity causes affected women to stop breastfeeding. We report a case of vasospasm of the nipple in which the patient experienced nipple pain and a separate lancinating pain that radiated through the breasts.

A 36-year-old woman presented with excruciating nipple and breast pain 3 weeks after delivering her first child. She had no history of smoking or Raynaud phenomenon. The nipple pain was triggered upon breastfeeding and exposure to cold. During these episodes, the nipples would initially blanch white, then turn purple and finally a deep red. The patient also experienced an episodic excruciating lancinating pain of the breast that would randomly and spontaneously radiate through either breast several times per day for 15 to 30 seconds. A workup including an antinuclear antibody test, complete blood cell count with differential, and comprehensive metabolic panel all were within reference range.

The patient was diagnosed with nipple vasospasm. Partial relief of nipple pain occurred after treatment with 30 mg daily of nifedipine; 60 mg daily resulted in complete control, allowing the patient to breastfeed without discomfort, but the lancinating pain continued unabated. The patient could not discontinue breastfeeding because her child was intolerant to formula. She became despondent, as she could find no relief from the pain that she found to be intolerable. Because the patient’s description was reminiscent of the lancinating pain seen in postherpetic neuralgia, a trial of pregabalin was prescribed. A dosage of 75 mg twice daily resulted in near-complete resolution of the pain. After 3 months, the patient successfully weaned her child from breast milk to formula, and the nipple and breast pain promptly resolved. The baby experienced no adverse effects from the patient’s use of pregabalin.

This condition was first described by Gunther¹ in 1970 as initial blanching of the nipple followed by a mulberry color. It was termed psychosomatic sore nipples.¹ Lawlor-Smith and Lawlor-Smith² described the condition in 1997 and termed it vasospasm of the nipple. They reported 5 patients who experienced debilitating nipple pain as well as the triphasic color change of Raynaud phenomenon or a biphasic color change (white and blue). Two patients had a history of Raynaud phenomenon affecting the digits before their first pregnancy.² Anderson et al³ presented 12 breastfeeding women with Raynaud phenomenon of the nipple; only 1 patient had a history of Raynaud phenomenon. In this series, all 6 women who chose to try nifedipine responded well to the drug.³ 

Raynaud phenomenon of the nipple also has been reported to be associated with the use of labetalol.⁴ In this case, the patient had a history of Raynaud phenomenon affecting the toes and nipples on cold days. In 2 subsequent pregnancies she was treated with labetalol for pregnancy-induced hypertension, which resulted in severe nipple pain with each pregnancy unrelated to cold weather. Unlike other cases, this patient experienced antenatal symptoms in addition to the typical postnatal symptoms. The nipple pain resolved with discontinuation of the labetalol.⁴

Barrett et al⁵ conducted a retrospective review of medical records of 88 breastfeeding mothers who presented with nipple pain and dermatitis. They defined the criteria for Raynaud phenomenon of the nipple as chronic deep breast pain (in general lasting >4 weeks) that responded to therapy for the condition and had at least 2 of the following characteristics: (1) observed or self-reported color changes of the nipple, especially with cold exposure (white, blue, or red); (2) cold sensitivity or color changes of the hands or feet with cold exposure; or (3) failed therapy with oral antifungals. Using these criteria, they diagnosed 22 women (25%) with Raynaud phenomenon of the nipple; 20 (91%) reported a history of cold sensitivity or color change of acral surfaces. Of 12 patients who received and tolerated nifedipine use, 10 (83%) reported decreased pain or complete resolution. This series described breast or nipple pain, whereas other reported cases only described nipple pain. The authors described a sharp, shooting, or stabbing pain—qualifications not previously noted.⁵ Our patient experienced both nipple pain and a lancinating breast pain consistent with the cases reported by Barrett et al.⁵

The nipple pain and treatment response in our patient was typical of previously reported cases of vasospasm of the nipple in breastfeeding women; however, Barrett et al⁵ did not describe individual patients who exhibited the dual nature of the pain described in our patient. The nipple pain experienced during breastfeeding in our patient was successfully treated with nifedipine. We report the successful treatment of the separate lancinating pain with pregabalin.

To the Editor:

A 33-year-old woman who was otherwise healthy presented with itchy wheals that developed within 15 to 20 minutes of removing leg hair with an electric epilator. Furthermore, she reported that small hives often developed after waxing the legs with warm wax. All lesions spontaneously disappeared within 3 hours; depilatory creams and shaving did not trigger urticarial lesions. She had no history of atopy or prior episodes of spontaneous urticaria. Symptomatic dermographism also was not reported. Classic physical stimuli that could be associated with the use of an electric epilator, such as heat, vibration, and pressure, did not elicit lesions.

Physical examination showed no active lesions. Dermographism was not inducible by stroking the patient’s skin with a blunt object. She brought personal photographs that showed erythematous follicular hives measuring 1 to 3 mm in diameter located on the distal legs (Figure). In accordance with these findings, she was diagnosed with an unusual form of physical urticaria likely resulting from hair traction and was prescribed oral H1 antihistamines to be taken a few days before and after hair removal.

Özkaya and Yazganog˘lu¹ proposed that follicular dermographism should be differentiated from physical urticaria. This variant of dermographism is characterized by discrete urticarial papules appearing at the location of hair follicles after having stroked the skin with a blunt object.^1,8 These lesions usually disappear within 30 minutes.⁸ Given that none of the reported cases presented dermographism on examination tests, we agree with Özkaya and Yazganog˘lu¹ that this phenomenon of traction urticaria likely is a different condition than follicular dermographism, even though intraindividual variability sometimes can be seen in dermographism skin tests.⁷

We present a unique form of urticaria that easily can be misdiagnosed as pseudofolliculitis, which tends to be more commonly associated with the use of electric epilators.

To the Editor:

A 33-year-old woman who was otherwise healthy presented with itchy wheals that developed within 15 to 20 minutes of removing leg hair with an electric epilator. Furthermore, she reported that small hives often developed after waxing the legs with warm wax. All lesions spontaneously disappeared within 3 hours; depilatory creams and shaving did not trigger urticarial lesions. She had no history of atopy or prior episodes of spontaneous urticaria. Symptomatic dermographism also was not reported. Classic physical stimuli that could be associated with the use of an electric epilator, such as heat, vibration, and pressure, did not elicit lesions.

Physical examination showed no active lesions. Dermographism was not inducible by stroking the patient’s skin with a blunt object. She brought personal photographs that showed erythematous follicular hives measuring 1 to 3 mm in diameter located on the distal legs (Figure). In accordance with these findings, she was diagnosed with an unusual form of physical urticaria likely resulting from hair traction and was prescribed oral H1 antihistamines to be taken a few days before and after hair removal.

Özkaya and Yazganog˘lu¹ proposed that follicular dermographism should be differentiated from physical urticaria. This variant of dermographism is characterized by discrete urticarial papules appearing at the location of hair follicles after having stroked the skin with a blunt object.^1,8 These lesions usually disappear within 30 minutes.⁸ Given that none of the reported cases presented dermographism on examination tests, we agree with Özkaya and Yazganog˘lu¹ that this phenomenon of traction urticaria likely is a different condition than follicular dermographism, even though intraindividual variability sometimes can be seen in dermographism skin tests.⁷

We present a unique form of urticaria that easily can be misdiagnosed as pseudofolliculitis, which tends to be more commonly associated with the use of electric epilators.

To the Editor:

A 33-year-old woman who was otherwise healthy presented with itchy wheals that developed within 15 to 20 minutes of removing leg hair with an electric epilator. Furthermore, she reported that small hives often developed after waxing the legs with warm wax. All lesions spontaneously disappeared within 3 hours; depilatory creams and shaving did not trigger urticarial lesions. She had no history of atopy or prior episodes of spontaneous urticaria. Symptomatic dermographism also was not reported. Classic physical stimuli that could be associated with the use of an electric epilator, such as heat, vibration, and pressure, did not elicit lesions.

Physical examination showed no active lesions. Dermographism was not inducible by stroking the patient’s skin with a blunt object. She brought personal photographs that showed erythematous follicular hives measuring 1 to 3 mm in diameter located on the distal legs (Figure). In accordance with these findings, she was diagnosed with an unusual form of physical urticaria likely resulting from hair traction and was prescribed oral H1 antihistamines to be taken a few days before and after hair removal.

Özkaya and Yazganog˘lu¹ proposed that follicular dermographism should be differentiated from physical urticaria. This variant of dermographism is characterized by discrete urticarial papules appearing at the location of hair follicles after having stroked the skin with a blunt object.^1,8 These lesions usually disappear within 30 minutes.⁸ Given that none of the reported cases presented dermographism on examination tests, we agree with Özkaya and Yazganog˘lu¹ that this phenomenon of traction urticaria likely is a different condition than follicular dermographism, even though intraindividual variability sometimes can be seen in dermographism skin tests.⁷

We present a unique form of urticaria that easily can be misdiagnosed as pseudofolliculitis, which tends to be more commonly associated with the use of electric epilators.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Epidemiology and Transmission

Pediculus humanus corporis, commonly known as the human body louse, is one in a family of 3 ectoparasites of the same suborder that also encompasses pubic lice (Phthirus pubis) and head lice (Pediculus humanus capitis). Adults are approximately 2 mm in size, with the same life cycle as head lice (Figure 1). They require blood meals roughly 5 times per day and cannot survive longer than 2 days without feeding.¹ Although similar in structure to head lice, body lice differ behaviorally in that they do not reside on their human host’s body; instead, they infest the host’s clothing, localizing to seams (Figure 2), and migrate to the host for blood meals. In fact, based on this behavior, genetic analysis of early human body lice has been used to postulate when clothing was first used by humans as well as to determine early human migration patterns.^2,3

Although clinicians in developed countries may be less familiar with body lice compared to their counterparts, body lice nevertheless remain a global health concern in impoverished, densely populated areas, as well as in homeless populations due to poor hygiene. Transmission frequently occurs via physical contact with an affected individual and his/her personal items (eg, linens) via fomites.^4,5 Body louse infestation is more prevalent in homeless individuals who sleep outside vs in shelters; a history of pubic lice and lack of regular bathing have been reported as additional risk factors.⁶ Outbreaks have been noted in the wake of natural disasters, in the setting of political upheavals, and in refugee camps, as well as in individuals seeking political asylum.⁷ Unlike head and pubic lice, body lice can serve as vectors for infectious diseases including Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (louse-borne relapsing fever), Bartonella quintana (trench fever), and Yersinia pestis (plague).^5,8,9 Several Acinetobacter species were isolated from nearly one-third of collected body louse specimens in a French study.¹⁰ Additionally, serology for B quintana was found to be positive in up to 30% of cases in one United States urban homeless population.⁴

Clinical Manifestations

Patients often present with generalized pruritus, usually considerably more severe than with P humanus capitis, with lesions concentrated on the trunk.¹¹ In addition to often impetiginized, self-inflicted excoriations, feeding sites may present as erythematous macules (Figure 3), papules, or papular urticaria with a central hemorrhagic punctum. Extensive infestation also can manifest as the colloquial vagabond disease, characterized by postinflammatory hyperpigmentation and thickening of the involved skin. Remarkably, patients also may present with considerable iron-deficiency anemia secondary to high parasite load and large volume blood feeding. Multiple case reports have demonstrated associated morbidity.^12-14 The differential diagnosis for pediculosis may include scabies, lichen simplex chronicus, and eczematous dermatitis, though the clinician should prudently consider whether both scabies and pediculosis may be present, as coexistence is possible.^4,15

Diagnosis

Diagnosis can be reached by visualizing adult lice, nymphs, or viable nits on the body or more commonly within inner clothing seams; nits also fluoresce under Wood light.¹⁵ Although dermoscopy has proven useful for increased sensitivity and differentiation between viable and hatched nits, the insects also can be viewed with the unaided eye.¹⁶

Treatment: New Concerns and Strategies

The mainstay of treatment for body lice has long consisted of thorough washing and drying of all clothing and linens in a hot dryer. Treatment can be augmented with the addition of pharmacotherapy, plus antibiotics as warranted for louse-borne disease. Pharmacologic intervention often is used in cases of mass infestation and is similar to head lice.

Options for head lice include topical permethrin, malathion, lindane, spinosad, benzyl alcohol, and ivermectin. Pyrethroids, derived from the chrysanthemum, generally are considered safe for human use with a side-effect profile limited to irritation and allergy¹⁷; however, neurotoxicity and leukemia are clinical concerns, with an association more recently shown between large-volume use of pyrethroids and acute lymphoblastic leukemia.^18,19 Use of lindane is not recommended due to a greater potential for central nervous system neurotoxicity, manifested by seizures, with repeated large surface application. Malathion is problematic due to the risk for mucosal irritation, flammability of some formulations, and theoretical organophosphate poisoning, as its mechanism of action involves inhibition of acetylcholinesterase.¹⁵ However, in the context of head lice treatment, a randomized controlled trial reported no incidence of acetylcholinesterase inhibition.²⁰ Spinosad, manufactured from the soil bacterium Saccharopolyspora spinosa, functions similarly by interfering with the nicotinic acetylcholine receptor and also carries a risk for skin irritation.²¹ Among all the treatment options, we prefer benzyl alcohol, particularly in the context of resistance, as it is effective via a physical mechanism of action and lacks notable neurotoxic effects to the host. Use of benzyl alcohol is approved for patients as young as 6 months; it functions by asphyxiating the lice via paralysis of the respiratory spiracle with occlusion by inert ingredients. Itching, episodic numbness, and scalp or mucosal irritation are possible complications of treatment.²²

Treatment resistance of body lice has increased in recent years, warranting exploration of additional management strategies. Moreover, developing resistance to lindane and malathion has been reported.²³ Resistance to pyrethroids has been attributed to mutations in a voltage-gated sodium channel, one of which was universally present in the sampling of a single population.²⁴ A randomized controlled trial showed that off-label oral ivermectin 400 μg/kg was superior to malathion lotion 0.5% in difficult-to-treat cases of head lice²⁵; utility of oral ivermectin also has been reported in body lice.²⁶ In vitro studies also have shown promise for pursuing synergistic treatment of body lice with both ivermectin and antibiotics.²⁷

A novel primary prophylaxis approach for at-risk homeless individuals recently utilized permethrin-impregnated underwear. Although the intervention provided short-term infestation improvement, longer-term use did not show improvement from placebo and also increased prevalence of permethrin-resistant haplotypes.²

Epidemiology and Transmission

Pediculus humanus corporis, commonly known as the human body louse, is one in a family of 3 ectoparasites of the same suborder that also encompasses pubic lice (Phthirus pubis) and head lice (Pediculus humanus capitis). Adults are approximately 2 mm in size, with the same life cycle as head lice (Figure 1). They require blood meals roughly 5 times per day and cannot survive longer than 2 days without feeding.¹ Although similar in structure to head lice, body lice differ behaviorally in that they do not reside on their human host’s body; instead, they infest the host’s clothing, localizing to seams (Figure 2), and migrate to the host for blood meals. In fact, based on this behavior, genetic analysis of early human body lice has been used to postulate when clothing was first used by humans as well as to determine early human migration patterns.^2,3

Although clinicians in developed countries may be less familiar with body lice compared to their counterparts, body lice nevertheless remain a global health concern in impoverished, densely populated areas, as well as in homeless populations due to poor hygiene. Transmission frequently occurs via physical contact with an affected individual and his/her personal items (eg, linens) via fomites.^4,5 Body louse infestation is more prevalent in homeless individuals who sleep outside vs in shelters; a history of pubic lice and lack of regular bathing have been reported as additional risk factors.⁶ Outbreaks have been noted in the wake of natural disasters, in the setting of political upheavals, and in refugee camps, as well as in individuals seeking political asylum.⁷ Unlike head and pubic lice, body lice can serve as vectors for infectious diseases including Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (louse-borne relapsing fever), Bartonella quintana (trench fever), and Yersinia pestis (plague).^5,8,9 Several Acinetobacter species were isolated from nearly one-third of collected body louse specimens in a French study.¹⁰ Additionally, serology for B quintana was found to be positive in up to 30% of cases in one United States urban homeless population.⁴

Clinical Manifestations

Patients often present with generalized pruritus, usually considerably more severe than with P humanus capitis, with lesions concentrated on the trunk.¹¹ In addition to often impetiginized, self-inflicted excoriations, feeding sites may present as erythematous macules (Figure 3), papules, or papular urticaria with a central hemorrhagic punctum. Extensive infestation also can manifest as the colloquial vagabond disease, characterized by postinflammatory hyperpigmentation and thickening of the involved skin. Remarkably, patients also may present with considerable iron-deficiency anemia secondary to high parasite load and large volume blood feeding. Multiple case reports have demonstrated associated morbidity.^12-14 The differential diagnosis for pediculosis may include scabies, lichen simplex chronicus, and eczematous dermatitis, though the clinician should prudently consider whether both scabies and pediculosis may be present, as coexistence is possible.^4,15

Diagnosis

Diagnosis can be reached by visualizing adult lice, nymphs, or viable nits on the body or more commonly within inner clothing seams; nits also fluoresce under Wood light.¹⁵ Although dermoscopy has proven useful for increased sensitivity and differentiation between viable and hatched nits, the insects also can be viewed with the unaided eye.¹⁶

Treatment: New Concerns and Strategies

The mainstay of treatment for body lice has long consisted of thorough washing and drying of all clothing and linens in a hot dryer. Treatment can be augmented with the addition of pharmacotherapy, plus antibiotics as warranted for louse-borne disease. Pharmacologic intervention often is used in cases of mass infestation and is similar to head lice.

Options for head lice include topical permethrin, malathion, lindane, spinosad, benzyl alcohol, and ivermectin. Pyrethroids, derived from the chrysanthemum, generally are considered safe for human use with a side-effect profile limited to irritation and allergy¹⁷; however, neurotoxicity and leukemia are clinical concerns, with an association more recently shown between large-volume use of pyrethroids and acute lymphoblastic leukemia.^18,19 Use of lindane is not recommended due to a greater potential for central nervous system neurotoxicity, manifested by seizures, with repeated large surface application. Malathion is problematic due to the risk for mucosal irritation, flammability of some formulations, and theoretical organophosphate poisoning, as its mechanism of action involves inhibition of acetylcholinesterase.¹⁵ However, in the context of head lice treatment, a randomized controlled trial reported no incidence of acetylcholinesterase inhibition.²⁰ Spinosad, manufactured from the soil bacterium Saccharopolyspora spinosa, functions similarly by interfering with the nicotinic acetylcholine receptor and also carries a risk for skin irritation.²¹ Among all the treatment options, we prefer benzyl alcohol, particularly in the context of resistance, as it is effective via a physical mechanism of action and lacks notable neurotoxic effects to the host. Use of benzyl alcohol is approved for patients as young as 6 months; it functions by asphyxiating the lice via paralysis of the respiratory spiracle with occlusion by inert ingredients. Itching, episodic numbness, and scalp or mucosal irritation are possible complications of treatment.²²

Treatment resistance of body lice has increased in recent years, warranting exploration of additional management strategies. Moreover, developing resistance to lindane and malathion has been reported.²³ Resistance to pyrethroids has been attributed to mutations in a voltage-gated sodium channel, one of which was universally present in the sampling of a single population.²⁴ A randomized controlled trial showed that off-label oral ivermectin 400 μg/kg was superior to malathion lotion 0.5% in difficult-to-treat cases of head lice²⁵; utility of oral ivermectin also has been reported in body lice.²⁶ In vitro studies also have shown promise for pursuing synergistic treatment of body lice with both ivermectin and antibiotics.²⁷

A novel primary prophylaxis approach for at-risk homeless individuals recently utilized permethrin-impregnated underwear. Although the intervention provided short-term infestation improvement, longer-term use did not show improvement from placebo and also increased prevalence of permethrin-resistant haplotypes.²

Epidemiology and Transmission

Pediculus humanus corporis, commonly known as the human body louse, is one in a family of 3 ectoparasites of the same suborder that also encompasses pubic lice (Phthirus pubis) and head lice (Pediculus humanus capitis). Adults are approximately 2 mm in size, with the same life cycle as head lice (Figure 1). They require blood meals roughly 5 times per day and cannot survive longer than 2 days without feeding.¹ Although similar in structure to head lice, body lice differ behaviorally in that they do not reside on their human host’s body; instead, they infest the host’s clothing, localizing to seams (Figure 2), and migrate to the host for blood meals. In fact, based on this behavior, genetic analysis of early human body lice has been used to postulate when clothing was first used by humans as well as to determine early human migration patterns.^2,3

Although clinicians in developed countries may be less familiar with body lice compared to their counterparts, body lice nevertheless remain a global health concern in impoverished, densely populated areas, as well as in homeless populations due to poor hygiene. Transmission frequently occurs via physical contact with an affected individual and his/her personal items (eg, linens) via fomites.^4,5 Body louse infestation is more prevalent in homeless individuals who sleep outside vs in shelters; a history of pubic lice and lack of regular bathing have been reported as additional risk factors.⁶ Outbreaks have been noted in the wake of natural disasters, in the setting of political upheavals, and in refugee camps, as well as in individuals seeking political asylum.⁷ Unlike head and pubic lice, body lice can serve as vectors for infectious diseases including Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (louse-borne relapsing fever), Bartonella quintana (trench fever), and Yersinia pestis (plague).^5,8,9 Several Acinetobacter species were isolated from nearly one-third of collected body louse specimens in a French study.¹⁰ Additionally, serology for B quintana was found to be positive in up to 30% of cases in one United States urban homeless population.⁴

Clinical Manifestations

Patients often present with generalized pruritus, usually considerably more severe than with P humanus capitis, with lesions concentrated on the trunk.¹¹ In addition to often impetiginized, self-inflicted excoriations, feeding sites may present as erythematous macules (Figure 3), papules, or papular urticaria with a central hemorrhagic punctum. Extensive infestation also can manifest as the colloquial vagabond disease, characterized by postinflammatory hyperpigmentation and thickening of the involved skin. Remarkably, patients also may present with considerable iron-deficiency anemia secondary to high parasite load and large volume blood feeding. Multiple case reports have demonstrated associated morbidity.^12-14 The differential diagnosis for pediculosis may include scabies, lichen simplex chronicus, and eczematous dermatitis, though the clinician should prudently consider whether both scabies and pediculosis may be present, as coexistence is possible.^4,15

Diagnosis

Diagnosis can be reached by visualizing adult lice, nymphs, or viable nits on the body or more commonly within inner clothing seams; nits also fluoresce under Wood light.¹⁵ Although dermoscopy has proven useful for increased sensitivity and differentiation between viable and hatched nits, the insects also can be viewed with the unaided eye.¹⁶

Treatment: New Concerns and Strategies

The mainstay of treatment for body lice has long consisted of thorough washing and drying of all clothing and linens in a hot dryer. Treatment can be augmented with the addition of pharmacotherapy, plus antibiotics as warranted for louse-borne disease. Pharmacologic intervention often is used in cases of mass infestation and is similar to head lice.

Options for head lice include topical permethrin, malathion, lindane, spinosad, benzyl alcohol, and ivermectin. Pyrethroids, derived from the chrysanthemum, generally are considered safe for human use with a side-effect profile limited to irritation and allergy¹⁷; however, neurotoxicity and leukemia are clinical concerns, with an association more recently shown between large-volume use of pyrethroids and acute lymphoblastic leukemia.^18,19 Use of lindane is not recommended due to a greater potential for central nervous system neurotoxicity, manifested by seizures, with repeated large surface application. Malathion is problematic due to the risk for mucosal irritation, flammability of some formulations, and theoretical organophosphate poisoning, as its mechanism of action involves inhibition of acetylcholinesterase.¹⁵ However, in the context of head lice treatment, a randomized controlled trial reported no incidence of acetylcholinesterase inhibition.²⁰ Spinosad, manufactured from the soil bacterium Saccharopolyspora spinosa, functions similarly by interfering with the nicotinic acetylcholine receptor and also carries a risk for skin irritation.²¹ Among all the treatment options, we prefer benzyl alcohol, particularly in the context of resistance, as it is effective via a physical mechanism of action and lacks notable neurotoxic effects to the host. Use of benzyl alcohol is approved for patients as young as 6 months; it functions by asphyxiating the lice via paralysis of the respiratory spiracle with occlusion by inert ingredients. Itching, episodic numbness, and scalp or mucosal irritation are possible complications of treatment.²²

Treatment resistance of body lice has increased in recent years, warranting exploration of additional management strategies. Moreover, developing resistance to lindane and malathion has been reported.²³ Resistance to pyrethroids has been attributed to mutations in a voltage-gated sodium channel, one of which was universally present in the sampling of a single population.²⁴ A randomized controlled trial showed that off-label oral ivermectin 400 μg/kg was superior to malathion lotion 0.5% in difficult-to-treat cases of head lice²⁵; utility of oral ivermectin also has been reported in body lice.²⁶ In vitro studies also have shown promise for pursuing synergistic treatment of body lice with both ivermectin and antibiotics.²⁷

A novel primary prophylaxis approach for at-risk homeless individuals recently utilized permethrin-impregnated underwear. Although the intervention provided short-term infestation improvement, longer-term use did not show improvement from placebo and also increased prevalence of permethrin-resistant haplotypes.²

MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).

The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.

Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.

Dr. Stander presented the results of a 20-center, double-blind, phase 2b clinical trial in which 70 patients with prurigo nodularis were randomized to subcutaneous nemolizumab at 0.5 mg/kg or placebo at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.

The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.

“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.

The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.

Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.

Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.

Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.

Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.

The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.

Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.

[email protected]

MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).

The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.

Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.

Dr. Stander presented the results of a 20-center, double-blind, phase 2b clinical trial in which 70 patients with prurigo nodularis were randomized to subcutaneous nemolizumab at 0.5 mg/kg or placebo at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.

The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.

“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.

The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.

Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.

Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.

Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.

Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.

The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.

Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.

[email protected]

MADRID – Nemolizumab, an investigational humanized monoclonal antibody targeting the interleukin-31 receptor alpha subunit, achieved rapid and clinically meaningful improvement in both itch and skin lesions of severe prurigo nodularis in a phase 2b, randomized trial, Sonja Stander, MD, said at the annual congress of the European Academy of Dermatology and Venereology.

“We saw onset of pruritus improvement in week 1 and onset of lesion healing at week 4,” reported Dr. Stander, professor of dermatology and neurodermatology and head of the Center for Chronic Pruritus at the University of Münster (Germany).

The study results confirm IL-31 signaling as an important therapeutic target in prurigo nodularis and herald the arrival of nemolizumab as a promising potential therapy for severely affected patients, she added.

Prurigo nodularis is a chronic, highly pruritic disease that is difficult to treat and carries a high disease burden. While the disease’s pathogenesis is not completely understood, IL-31 is up-regulated in affected patients. And IL-31, a proinflammatory and immunomodulatory cytokine, is known to have a broad range of actions, including serving as a link between the immune and neural systems, as well as induction of itch and skin lesions.

Dr. Stander presented the results of a 20-center, double-blind, phase 2b clinical trial in which 70 patients with prurigo nodularis were randomized to subcutaneous nemolizumab at 0.5 mg/kg or placebo at weeks 0, 4, and 8, then followed off therapy out to week 18. These were severely affected patients: their mean weekly peak pruritus score on a 0-10 numeric rating scale was 8.4, with 7 being the accepted threshold for severe itch. The group had a mean Dermatologic Life Quality Index score of 16.4; 40% of patients had more than 100 nodules on their body, and the rest had 20-100.

The primary endpoint was the percentage decrease in the peak pruritus score from baseline to week 4, at which point they had only received one dose. The nemolizumab group averaged a 53.4% reduction, compared with 15.3% in placebo-treated controls. At week 12, a full month after the final injection, the split was 63.2% versus 20.2%. And at week 18, the nemolizumab group maintained a mean 58.2% reduction from baseline versus 20.9% in controls.

“The effect starts at week 1, with a 26% reduction in itch intensity in the nemolizumab group, compared to 6.7% with placebo,” the dermatologist observed.

The absolute decrease in weekly peak pruritus score at week 12 was 5.2 points with nemolizumab and 1.7 points with placebo.

Among the secondary endpoints was achievement of an Investigator Global Assessment score of 0-1, meaning clear or almost clear of skin lesions. The rate in the nemolizumab group climbed steadily from week 4 on, reaching 38.2% and still rising without a plateau at week 18, versus 5.6% in controls.

Another secondary endpoint was 75% or greater healing on the 7-item Prurigo Activity Scale. By week 4 there was already a statistically significant between-group difference: 23.5% versus 11.2%. Once again, in the nemolizumab group, this rate climbed without a plateau through the study’s end at week 18, by which point it was 44.1%, compared with 8.4% among those on placebo.

Scores on the Dermatologic Life Quality Index improved by an average of 10.2 points at week 4 in patients on nemolizumab, compared with 6 points among controls.

Self-reported sleep disturbance scores improved by 56% at week 4 in the nemolizumab group and 22.9% with placebo.

The safety profile of nemolizumab was similar to that of placebo, with roughly 5.7% of patients in each study arm withdrawing because of treatment-emergent adverse events. Unlike in the positive studies of the IL-31 inhibitor in patients with atopic dermatitis – another potential indication under active investigation – there was no signal of an increased risk of staphylococcal skin infections, conjunctivitis, or head and neck dermatitis in patients on nemolizumab for prurigo nodularis. Patients with comorbid atopic dermatitis were excluded from the prurigo nodularis trial in order to get a clearer picture of the biologic’s efficacy and safety specifically for that condition.

Dr. Stander reported serving as a consultant to Galderma, the study sponsor, as well as numerous other pharmaceutical companies.

[email protected]

To the Editor:

First documented in 1904,¹ solar urticaria is an IgE-induced condition that predominantly occurs in women aged 20 to 50 years. Worldwide prevalence and incidence information is lacking, but it is known to occur in up to 0.4% of urticaria cases.² Solar urticaria is characterized by pruritus of the skin with erythematous wheals and flares in reaction to sunlight exposure, even despite partial protection by barriers such as glass or clothing.^2,3 It can have an acute or chronic presentation caused by visible or UV light wavelengths. Solar urticaria can lead to debilitating symptoms and psychological stressors that can severely impact a patient’s well-being and also may be accompanied by conditions such as polymorphous light eruption, angioedema, or vasculitis.⁴ Standard treatments include first- and second-generation antihistamines, which are efficacious approximately 50% of the time, as well as phototherapy, which can be time consuming and a burden on patients who work or go to school full time.² Other possible treatment modalities include plasmapheresis, intravenous immunoglobulins, steroids, cyclosporine, and anti-IgE recombinant monoclonal antibody injections.^5,6 We present the case of a patient who was successfully treated with subcutaneous injections of omalizumab every 3 weeks to add to the growing number of case reports of treatment of solar urticaria.

A 30-year-old woman with Fitzpatrick skin type III and a 9-year history of solar urticaria was referred to the Department of Allergy and Immunology by her primary care physician. The patient reported that redness, swelling, and itching would occur on sun-exposed areas of the skin after approximately 10 minutes of exposure despite daily sunscreen application. She had been successfully treated with hydroxychloroquine 400 mg once daily after her first formal evaluation by dermatology 4 years prior to the current presentation. She subsequently self-discontinued treatment after 8 months of treatment due to resolution of symptoms. She noted the symptoms had returned upon relocating to Hawaii after living in the continental United States and Italy. Initially she was restarted on hydroxychloroquine 200 mg once daily and 4-times the recommended daily dose of second-generation antihistamines without relief. The hydroxychloroquine dosage subsequently was increased to 400 mg once daily, but her symptoms did not resolve.

On physical examination, sun-exposed areas of the skin showed marked macular erythema with discrete erythematous lines of demarcation observed between exposed and unexposed skin. The patient also reported concomitant pruritus, which antihistamines did not alleviate. A maximum 1-year course of cyclosporine 300 mg once daily initially was planned but was discontinued due to immediate onset of severe nausea and emesis after the first dose as well as continued outbreaks of urticaria for 1 month after incrementally increasing by 100 mg from a starting dose of 100 mg.

After discussion with the dermatology department, a trial of omalizumab was started because the daily impact of a UV light sensitization course was not feasible with her work schedule, and serum IgE blood level was 560.4 µg/L (reference range, 0–1500 µg/L). The patient was started on a regimen of omalizumab 300 mg (subcutaneous injections) every 2 weeks with noted improvement after the third dose, with no urticarial symptoms after sun exposure. After 2 months, the dosage interval was increased to every 4 weeks given her level of improvement, but her symptoms recurred. The treatment regimen was then changed to every 3 weeks. The patient was symptom free for a period of 10 months on this regimen, followed by only 1 outbreak of erythema and urticaria, which occurred 1 day prior to a scheduled omalizumab injection. Symptoms have otherwise been well controlled to date on omalizumab.

Solar urticaria is a poorly understood phenomenon that has no clear prognostic indicators; therefore, diagnosis often is made based on the patient’s history and physical examination. Further testing to confirm the diagnosis can be performed using specific wavelengths of UV light to determine which band of light affects patients most; however, the wavelength can change over time, leading to less clinical significance, and may decrease efficacy of phototherapy.² Solar urticaria has no clear predisposing factors, and treatments to date have been moderately successful. Exposure to sunlight is thought to initiate an alteration in a skin or serum chromophore or photoallergen, which then causes subsequent cross-linking and IgE-dependent release of histamine as well as other mediators such as cytokines, eicosanoids, and proteases with mast cell degranulation.⁷

Omalizumab is a recombinant humanized monoclonal IgG1 antibody targeting the methylated IgE Cε3 domain that initially was marketed toward controlling IgE-mediated moderate to severe asthma recalcitrant to standard treatments. It has since received approval from the US Food and Drug Administration for treatment of chronic idiopathic urticaria after first being noticed to serendipitously treat a patient with cold urticaria and asthma in 2006.^4,7,8 It was then first documented to successfully treat solar urticaria in 2008.⁶ The safety profile of omalizumab makes it a more favorable choice when compared to other immunomodulating treatments, with the most serious adverse reaction being anaphylaxis, occurring in 0.2% of patients in a postmarketing study.⁹ It functions through binding to free IgE at a region necessary for IgE to bind at low- and high-affinity receptors but not to immunoglobulins already bound to cells, thus theoretically preventing activation of mast cells or basophils.¹⁰ It also has been suggested that low steady-state values are needed to see continued benefit from the drug,¹⁰ which may have been seen in our patient after having an outbreak just prior to receiving an injection; however, prior reports have shown benefit unrelated to total IgE levels, with improvement after days to 4 months.^4,10,11 One case report showed no response after 4 doses; it is unknown if this patient was tested for clinical improvement to omalizumab through further immunoglobulin analysis, but treatment response is important to consider when deciding on whether to use this drug in future patients.¹² It is unknown why some patients will respond to omalizumab, others will partially respond, and others will not respond, which can be ascertained either through quality-of-life improvement or lack thereof.

In our experience, omalizumab is a viable option to consider in patients with solar urticaria that is recalcitrant to standard treatments and elevated IgE levels for whom other treatments are either too time consuming or have side-effect profiles that are not tolerable to the patient. If the patient has concomitant asthma, there may be additional therapeutic benefit. Further research is needed with regard to a cost-benefit analysis of omalizumab and whether using such a costly drug outweighs the cost associated with time and resources utilized with repeat clinic visits if other standard treatments are not effective.¹³

To the Editor:

First documented in 1904,¹ solar urticaria is an IgE-induced condition that predominantly occurs in women aged 20 to 50 years. Worldwide prevalence and incidence information is lacking, but it is known to occur in up to 0.4% of urticaria cases.² Solar urticaria is characterized by pruritus of the skin with erythematous wheals and flares in reaction to sunlight exposure, even despite partial protection by barriers such as glass or clothing.^2,3 It can have an acute or chronic presentation caused by visible or UV light wavelengths. Solar urticaria can lead to debilitating symptoms and psychological stressors that can severely impact a patient’s well-being and also may be accompanied by conditions such as polymorphous light eruption, angioedema, or vasculitis.⁴ Standard treatments include first- and second-generation antihistamines, which are efficacious approximately 50% of the time, as well as phototherapy, which can be time consuming and a burden on patients who work or go to school full time.² Other possible treatment modalities include plasmapheresis, intravenous immunoglobulins, steroids, cyclosporine, and anti-IgE recombinant monoclonal antibody injections.^5,6 We present the case of a patient who was successfully treated with subcutaneous injections of omalizumab every 3 weeks to add to the growing number of case reports of treatment of solar urticaria.

A 30-year-old woman with Fitzpatrick skin type III and a 9-year history of solar urticaria was referred to the Department of Allergy and Immunology by her primary care physician. The patient reported that redness, swelling, and itching would occur on sun-exposed areas of the skin after approximately 10 minutes of exposure despite daily sunscreen application. She had been successfully treated with hydroxychloroquine 400 mg once daily after her first formal evaluation by dermatology 4 years prior to the current presentation. She subsequently self-discontinued treatment after 8 months of treatment due to resolution of symptoms. She noted the symptoms had returned upon relocating to Hawaii after living in the continental United States and Italy. Initially she was restarted on hydroxychloroquine 200 mg once daily and 4-times the recommended daily dose of second-generation antihistamines without relief. The hydroxychloroquine dosage subsequently was increased to 400 mg once daily, but her symptoms did not resolve.

On physical examination, sun-exposed areas of the skin showed marked macular erythema with discrete erythematous lines of demarcation observed between exposed and unexposed skin. The patient also reported concomitant pruritus, which antihistamines did not alleviate. A maximum 1-year course of cyclosporine 300 mg once daily initially was planned but was discontinued due to immediate onset of severe nausea and emesis after the first dose as well as continued outbreaks of urticaria for 1 month after incrementally increasing by 100 mg from a starting dose of 100 mg.

After discussion with the dermatology department, a trial of omalizumab was started because the daily impact of a UV light sensitization course was not feasible with her work schedule, and serum IgE blood level was 560.4 µg/L (reference range, 0–1500 µg/L). The patient was started on a regimen of omalizumab 300 mg (subcutaneous injections) every 2 weeks with noted improvement after the third dose, with no urticarial symptoms after sun exposure. After 2 months, the dosage interval was increased to every 4 weeks given her level of improvement, but her symptoms recurred. The treatment regimen was then changed to every 3 weeks. The patient was symptom free for a period of 10 months on this regimen, followed by only 1 outbreak of erythema and urticaria, which occurred 1 day prior to a scheduled omalizumab injection. Symptoms have otherwise been well controlled to date on omalizumab.

Solar urticaria is a poorly understood phenomenon that has no clear prognostic indicators; therefore, diagnosis often is made based on the patient’s history and physical examination. Further testing to confirm the diagnosis can be performed using specific wavelengths of UV light to determine which band of light affects patients most; however, the wavelength can change over time, leading to less clinical significance, and may decrease efficacy of phototherapy.² Solar urticaria has no clear predisposing factors, and treatments to date have been moderately successful. Exposure to sunlight is thought to initiate an alteration in a skin or serum chromophore or photoallergen, which then causes subsequent cross-linking and IgE-dependent release of histamine as well as other mediators such as cytokines, eicosanoids, and proteases with mast cell degranulation.⁷

Omalizumab is a recombinant humanized monoclonal IgG1 antibody targeting the methylated IgE Cε3 domain that initially was marketed toward controlling IgE-mediated moderate to severe asthma recalcitrant to standard treatments. It has since received approval from the US Food and Drug Administration for treatment of chronic idiopathic urticaria after first being noticed to serendipitously treat a patient with cold urticaria and asthma in 2006.^4,7,8 It was then first documented to successfully treat solar urticaria in 2008.⁶ The safety profile of omalizumab makes it a more favorable choice when compared to other immunomodulating treatments, with the most serious adverse reaction being anaphylaxis, occurring in 0.2% of patients in a postmarketing study.⁹ It functions through binding to free IgE at a region necessary for IgE to bind at low- and high-affinity receptors but not to immunoglobulins already bound to cells, thus theoretically preventing activation of mast cells or basophils.¹⁰ It also has been suggested that low steady-state values are needed to see continued benefit from the drug,¹⁰ which may have been seen in our patient after having an outbreak just prior to receiving an injection; however, prior reports have shown benefit unrelated to total IgE levels, with improvement after days to 4 months.^4,10,11 One case report showed no response after 4 doses; it is unknown if this patient was tested for clinical improvement to omalizumab through further immunoglobulin analysis, but treatment response is important to consider when deciding on whether to use this drug in future patients.¹² It is unknown why some patients will respond to omalizumab, others will partially respond, and others will not respond, which can be ascertained either through quality-of-life improvement or lack thereof.

In our experience, omalizumab is a viable option to consider in patients with solar urticaria that is recalcitrant to standard treatments and elevated IgE levels for whom other treatments are either too time consuming or have side-effect profiles that are not tolerable to the patient. If the patient has concomitant asthma, there may be additional therapeutic benefit. Further research is needed with regard to a cost-benefit analysis of omalizumab and whether using such a costly drug outweighs the cost associated with time and resources utilized with repeat clinic visits if other standard treatments are not effective.¹³

To the Editor:

First documented in 1904,¹ solar urticaria is an IgE-induced condition that predominantly occurs in women aged 20 to 50 years. Worldwide prevalence and incidence information is lacking, but it is known to occur in up to 0.4% of urticaria cases.² Solar urticaria is characterized by pruritus of the skin with erythematous wheals and flares in reaction to sunlight exposure, even despite partial protection by barriers such as glass or clothing.^2,3 It can have an acute or chronic presentation caused by visible or UV light wavelengths. Solar urticaria can lead to debilitating symptoms and psychological stressors that can severely impact a patient’s well-being and also may be accompanied by conditions such as polymorphous light eruption, angioedema, or vasculitis.⁴ Standard treatments include first- and second-generation antihistamines, which are efficacious approximately 50% of the time, as well as phototherapy, which can be time consuming and a burden on patients who work or go to school full time.² Other possible treatment modalities include plasmapheresis, intravenous immunoglobulins, steroids, cyclosporine, and anti-IgE recombinant monoclonal antibody injections.^5,6 We present the case of a patient who was successfully treated with subcutaneous injections of omalizumab every 3 weeks to add to the growing number of case reports of treatment of solar urticaria.

A 30-year-old woman with Fitzpatrick skin type III and a 9-year history of solar urticaria was referred to the Department of Allergy and Immunology by her primary care physician. The patient reported that redness, swelling, and itching would occur on sun-exposed areas of the skin after approximately 10 minutes of exposure despite daily sunscreen application. She had been successfully treated with hydroxychloroquine 400 mg once daily after her first formal evaluation by dermatology 4 years prior to the current presentation. She subsequently self-discontinued treatment after 8 months of treatment due to resolution of symptoms. She noted the symptoms had returned upon relocating to Hawaii after living in the continental United States and Italy. Initially she was restarted on hydroxychloroquine 200 mg once daily and 4-times the recommended daily dose of second-generation antihistamines without relief. The hydroxychloroquine dosage subsequently was increased to 400 mg once daily, but her symptoms did not resolve.

On physical examination, sun-exposed areas of the skin showed marked macular erythema with discrete erythematous lines of demarcation observed between exposed and unexposed skin. The patient also reported concomitant pruritus, which antihistamines did not alleviate. A maximum 1-year course of cyclosporine 300 mg once daily initially was planned but was discontinued due to immediate onset of severe nausea and emesis after the first dose as well as continued outbreaks of urticaria for 1 month after incrementally increasing by 100 mg from a starting dose of 100 mg.

After discussion with the dermatology department, a trial of omalizumab was started because the daily impact of a UV light sensitization course was not feasible with her work schedule, and serum IgE blood level was 560.4 µg/L (reference range, 0–1500 µg/L). The patient was started on a regimen of omalizumab 300 mg (subcutaneous injections) every 2 weeks with noted improvement after the third dose, with no urticarial symptoms after sun exposure. After 2 months, the dosage interval was increased to every 4 weeks given her level of improvement, but her symptoms recurred. The treatment regimen was then changed to every 3 weeks. The patient was symptom free for a period of 10 months on this regimen, followed by only 1 outbreak of erythema and urticaria, which occurred 1 day prior to a scheduled omalizumab injection. Symptoms have otherwise been well controlled to date on omalizumab.

Solar urticaria is a poorly understood phenomenon that has no clear prognostic indicators; therefore, diagnosis often is made based on the patient’s history and physical examination. Further testing to confirm the diagnosis can be performed using specific wavelengths of UV light to determine which band of light affects patients most; however, the wavelength can change over time, leading to less clinical significance, and may decrease efficacy of phototherapy.² Solar urticaria has no clear predisposing factors, and treatments to date have been moderately successful. Exposure to sunlight is thought to initiate an alteration in a skin or serum chromophore or photoallergen, which then causes subsequent cross-linking and IgE-dependent release of histamine as well as other mediators such as cytokines, eicosanoids, and proteases with mast cell degranulation.⁷

Omalizumab is a recombinant humanized monoclonal IgG1 antibody targeting the methylated IgE Cε3 domain that initially was marketed toward controlling IgE-mediated moderate to severe asthma recalcitrant to standard treatments. It has since received approval from the US Food and Drug Administration for treatment of chronic idiopathic urticaria after first being noticed to serendipitously treat a patient with cold urticaria and asthma in 2006.^4,7,8 It was then first documented to successfully treat solar urticaria in 2008.⁶ The safety profile of omalizumab makes it a more favorable choice when compared to other immunomodulating treatments, with the most serious adverse reaction being anaphylaxis, occurring in 0.2% of patients in a postmarketing study.⁹ It functions through binding to free IgE at a region necessary for IgE to bind at low- and high-affinity receptors but not to immunoglobulins already bound to cells, thus theoretically preventing activation of mast cells or basophils.¹⁰ It also has been suggested that low steady-state values are needed to see continued benefit from the drug,¹⁰ which may have been seen in our patient after having an outbreak just prior to receiving an injection; however, prior reports have shown benefit unrelated to total IgE levels, with improvement after days to 4 months.^4,10,11 One case report showed no response after 4 doses; it is unknown if this patient was tested for clinical improvement to omalizumab through further immunoglobulin analysis, but treatment response is important to consider when deciding on whether to use this drug in future patients.¹² It is unknown why some patients will respond to omalizumab, others will partially respond, and others will not respond, which can be ascertained either through quality-of-life improvement or lack thereof.

In our experience, omalizumab is a viable option to consider in patients with solar urticaria that is recalcitrant to standard treatments and elevated IgE levels for whom other treatments are either too time consuming or have side-effect profiles that are not tolerable to the patient. If the patient has concomitant asthma, there may be additional therapeutic benefit. Further research is needed with regard to a cost-benefit analysis of omalizumab and whether using such a costly drug outweighs the cost associated with time and resources utilized with repeat clinic visits if other standard treatments are not effective.¹³

Half a million people. That’s pretty close to the population of Sacramento. It’s also the estimated number of adults living with chronic urticaria in the United States, according to analysis of a database including over 55 million individuals.

That cross-sectional analysis put the overall standardized prevalence of chronic urticaria in the United States at 0.23%, or 229.8 per 100,000 adults, with women’s prevalence well above at 309.3 per 100,000 (0.31%) and men well below at 145.5 per 100,000 (0.15%), Sara Wertenteil, BA, and her associates at Hofstra University, Hempstead, N.Y., wrote in the Journal of the American Academy of Dermatology.

Overall prevalence of chronic urticaria was similar for all age groups, ranging from 0.21% for those aged 18-29 years and those aged 30-39 years to 0.26% for those aged 40-49, and prevalence was higher for females than males in all age groups, the investigators reported.

“Epidemiologic studies estimating disease burden for chronic urticaria are sparse, [but this study] is based on one of the largest and most ethnically diversified population samples in the United States. It is also drawn from patients with all insurance types and self-pay patients across various types of health care settings and from all census regions,” Ms. Wertenteil and her associates wrote.


The study involved an IBM Watson Health database encompassing 27 participating integrated health care organizations and representing approximately 17% of the population. The analysis identified 69,570 adult patients with chronic urticaria, and the ratio of women to men was 2.7:1.

The senior author, Amit Garg, MD, has served as an advisor for AbbVie, Pfizer, Janssen, and Asana Biosciences.

[email protected]

SOURCE: Wertenteil S et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.064.

Half a million people. That’s pretty close to the population of Sacramento. It’s also the estimated number of adults living with chronic urticaria in the United States, according to analysis of a database including over 55 million individuals.

That cross-sectional analysis put the overall standardized prevalence of chronic urticaria in the United States at 0.23%, or 229.8 per 100,000 adults, with women’s prevalence well above at 309.3 per 100,000 (0.31%) and men well below at 145.5 per 100,000 (0.15%), Sara Wertenteil, BA, and her associates at Hofstra University, Hempstead, N.Y., wrote in the Journal of the American Academy of Dermatology.

Overall prevalence of chronic urticaria was similar for all age groups, ranging from 0.21% for those aged 18-29 years and those aged 30-39 years to 0.26% for those aged 40-49, and prevalence was higher for females than males in all age groups, the investigators reported.

“Epidemiologic studies estimating disease burden for chronic urticaria are sparse, [but this study] is based on one of the largest and most ethnically diversified population samples in the United States. It is also drawn from patients with all insurance types and self-pay patients across various types of health care settings and from all census regions,” Ms. Wertenteil and her associates wrote.


The study involved an IBM Watson Health database encompassing 27 participating integrated health care organizations and representing approximately 17% of the population. The analysis identified 69,570 adult patients with chronic urticaria, and the ratio of women to men was 2.7:1.

The senior author, Amit Garg, MD, has served as an advisor for AbbVie, Pfizer, Janssen, and Asana Biosciences.

[email protected]

SOURCE: Wertenteil S et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.064.

Half a million people. That’s pretty close to the population of Sacramento. It’s also the estimated number of adults living with chronic urticaria in the United States, according to analysis of a database including over 55 million individuals.

That cross-sectional analysis put the overall standardized prevalence of chronic urticaria in the United States at 0.23%, or 229.8 per 100,000 adults, with women’s prevalence well above at 309.3 per 100,000 (0.31%) and men well below at 145.5 per 100,000 (0.15%), Sara Wertenteil, BA, and her associates at Hofstra University, Hempstead, N.Y., wrote in the Journal of the American Academy of Dermatology.

Overall prevalence of chronic urticaria was similar for all age groups, ranging from 0.21% for those aged 18-29 years and those aged 30-39 years to 0.26% for those aged 40-49, and prevalence was higher for females than males in all age groups, the investigators reported.

“Epidemiologic studies estimating disease burden for chronic urticaria are sparse, [but this study] is based on one of the largest and most ethnically diversified population samples in the United States. It is also drawn from patients with all insurance types and self-pay patients across various types of health care settings and from all census regions,” Ms. Wertenteil and her associates wrote.


The study involved an IBM Watson Health database encompassing 27 participating integrated health care organizations and representing approximately 17% of the population. The analysis identified 69,570 adult patients with chronic urticaria, and the ratio of women to men was 2.7:1.

The senior author, Amit Garg, MD, has served as an advisor for AbbVie, Pfizer, Janssen, and Asana Biosciences.

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SOURCE: Wertenteil S et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.02.064.