Prolonged Drug-Induced Hypersensitivity Syndrome/DRESS With Alopecia Areata and Autoimmune Thyroiditis

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Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.1 Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.

 

Case Presentation

A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.

Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).2 A punch biopsy was confirmatory (Figure 2A).3 The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.



The patient was maintained on prednisone 70 to 80 mg daily for 2 months before improvement of the rash and pruritus. The prednisone was slowly tapered over a 6-week period and then discontinued. Shortly after discontinuation, the patient redeveloped erythroderma. Skin biopsy and complete blood count (17.3% eosinophilia) confirmed the suspected DIHS/DRESS relapse (Figure 2B). In addition, the patient reported upper respiratory tract symptoms and concurrently tested positive for human herpesvirus 6 (HHV-6). The patient was restarted on prednisone and low-dose narrow-band UVB (nbUVB) therapy was added. Over the following 2 months, they responded well to low-dose nbUVB therapy. By the end of nbUVB treatment, about 5 months after initial presentation, the patient’s erythroderma improved, eosinophilia resolved, and they were able to tolerate prednisone taper. Ten months after cessation of lamotrigine, prednisone was finally discontinued. Two weeks later, the patient was screened for adrenal insufficiency (AI) given the prolonged steroid course. Their serum morning cortisol level was within normal limits.

Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.

Discussion

DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.3 Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).4 Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.3 The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.5 Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.5 Overall mortality rate may be as high as 10% most commonly due to acute liver failure.5 Biopsy may be helpful in the diagnosis but is not always specific.5 Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).5 

The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.2 Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.6 Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.2 Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.7 Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.8

 

 



DIHS/DRESS syndrome has been associated with development of autoimmune diseases as long-term sequelae. The most commonly affected organs are the thyroid and pancreas; approximately 4.8% of patients develop autoimmune thyroiditis and 3.5% develop fulminant T1DM.9 The time from onset of DIHS/DRESS to development of autoimmune thyroiditis can range from 2 months to 2 years, whereas the range from DIHS/DRESS onset to fulminant T1DM is about 40 days.9 Alopecia had been reported in 1, occurring 4 months after DIHS/DRESS onset. Our patient’s alopecia areata and Hashimoto thyroiditis occurred 14 and 15 months after DIHS/DRESS presentation, respectively.

Treatment

For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.10 Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.11

A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.12 However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.12

The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.13 Patients may not regain full adrenal function for 12 to 18 months.14 Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.10

Conclusions

DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.12 Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.

References

1. RegiSCAR. Accessed June 3, 2022. http://www.regiscar.org

2. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): an update in 2019. Allergol Int. 2019;68(3):301-308. doi:10.1016/j.alit.2019.03.006

3. Wolfson AR, Zhou L, Li Y, Phadke NA, Chow OA, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome identified in the electronic health record allergy module. J Allergy Clin Immunol Pract. 2019;7(2):633-640. doi:10.1016/j.jaip.2018.08.013

4. Sasidharanpillai S, Govindan A, Riyaz N, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis. Indian J Dermatol Venereol Leprol. 2016;82(1):28. doi:10.4103/0378-6323.168934

5. Kardaun SH, Sekula P, Valeyrie‐Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501

6. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00879

7. Yang C-W, Cho Y-T, Hsieh Y-C, Hsu S-H, Chen K-L, Chu C-Y. The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183(5):909-919. doi:10.1111/bjd.18942

8. Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res. 2014;46(9):597-602. doi:10.1055/s-0034-1382053

9. Kano Y, Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276-282. doi:10.1111/1346-8138.12770

10. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017

11. Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of psychotropic drug-induced dress syndrome: a systematic review. Mayo Clin Proc. 2016;91(6):787-801. doi:10.1016/j.mayocp.2016.03.006

12. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of cyclosporine for the treatment of DRESS syndrome. JAMA Dermatol. 2020;156(6):704-706. doi:10.1001/jamadermatol.2020.0048

13. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi:10.1016/j.semarthrit.2016.03.001

14. Jamilloux Y, Liozon E, Pugnet G, et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS ONE. 2013;8(7):e68713. doi:10.1371/journal.pone.0068713

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2LT Kathleen Krivda, USAa; LTC John Campagna, MD, USAb; MAJ Salvatore Mignano, DO, USAc; and COL Sunghun Cho, MD, USAa
Correspondence: Kathleen Krivda ([email protected])

aUniformed Services University of the Health Sciences, Bethesda, Maryland
b1st Theater Sustainment Command, Fort Knox, Kentucky
cTripler Army Medical Center, Honolulu, Hawaii

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The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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Correspondence: Kathleen Krivda ([email protected])

aUniformed Services University of the Health Sciences, Bethesda, Maryland
b1st Theater Sustainment Command, Fort Knox, Kentucky
cTripler Army Medical Center, Honolulu, Hawaii

Author disclosures

The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Ethics and consent

The authors obtained written informed consent from the patient.

Author and Disclosure Information

2LT Kathleen Krivda, USAa; LTC John Campagna, MD, USAb; MAJ Salvatore Mignano, DO, USAc; and COL Sunghun Cho, MD, USAa
Correspondence: Kathleen Krivda ([email protected])

aUniformed Services University of the Health Sciences, Bethesda, Maryland
b1st Theater Sustainment Command, Fort Knox, Kentucky
cTripler Army Medical Center, Honolulu, Hawaii

Author disclosures

The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Ethics and consent

The authors obtained written informed consent from the patient.

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Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.1 Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.

 

Case Presentation

A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.

Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).2 A punch biopsy was confirmatory (Figure 2A).3 The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.



The patient was maintained on prednisone 70 to 80 mg daily for 2 months before improvement of the rash and pruritus. The prednisone was slowly tapered over a 6-week period and then discontinued. Shortly after discontinuation, the patient redeveloped erythroderma. Skin biopsy and complete blood count (17.3% eosinophilia) confirmed the suspected DIHS/DRESS relapse (Figure 2B). In addition, the patient reported upper respiratory tract symptoms and concurrently tested positive for human herpesvirus 6 (HHV-6). The patient was restarted on prednisone and low-dose narrow-band UVB (nbUVB) therapy was added. Over the following 2 months, they responded well to low-dose nbUVB therapy. By the end of nbUVB treatment, about 5 months after initial presentation, the patient’s erythroderma improved, eosinophilia resolved, and they were able to tolerate prednisone taper. Ten months after cessation of lamotrigine, prednisone was finally discontinued. Two weeks later, the patient was screened for adrenal insufficiency (AI) given the prolonged steroid course. Their serum morning cortisol level was within normal limits.

Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.

Discussion

DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.3 Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).4 Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.3 The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.5 Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.5 Overall mortality rate may be as high as 10% most commonly due to acute liver failure.5 Biopsy may be helpful in the diagnosis but is not always specific.5 Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).5 

The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.2 Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.6 Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.2 Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.7 Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.8

 

 



DIHS/DRESS syndrome has been associated with development of autoimmune diseases as long-term sequelae. The most commonly affected organs are the thyroid and pancreas; approximately 4.8% of patients develop autoimmune thyroiditis and 3.5% develop fulminant T1DM.9 The time from onset of DIHS/DRESS to development of autoimmune thyroiditis can range from 2 months to 2 years, whereas the range from DIHS/DRESS onset to fulminant T1DM is about 40 days.9 Alopecia had been reported in 1, occurring 4 months after DIHS/DRESS onset. Our patient’s alopecia areata and Hashimoto thyroiditis occurred 14 and 15 months after DIHS/DRESS presentation, respectively.

Treatment

For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.10 Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.11

A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.12 However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.12

The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.13 Patients may not regain full adrenal function for 12 to 18 months.14 Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.10

Conclusions

DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.12 Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.

Drug-induced hypersensitivity syndrome (DIHS), also called drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, is a potentially fatal drug-induced hypersensitivity reaction that is characterized by a cutaneous eruption, multiorgan involvement, viral reactivation, and hematologic abnormalities. As the nomenclature of this disease advances, consensus groups have adopted DIHS/DRESS to underscore that both names refer to the same clinical phenomenon.1 Autoimmune sequelae have been reported after DIHS/DRESS that include vitiligo, thyroid disease, and type 1 diabetes mellitus (T1DM). We present a case of lamotrigine-associated DIHS/DRESS complicated by an unusually prolonged course requiring oral corticosteroids and narrow-band ultraviolet B (UVB) treatment and with development of extensive alopecia areata and autoimmune thyroiditis.

 

Case Presentation

A 35-year-old female Filipino patient was prescribed lamotrigine 25 mg daily for bipolar II disorder and titrated to 100 mg twice daily after 1 month. One week after the increase, the patient developed a diffuse morbilliform rash covering their entire body along with facial swelling and generalized pruritus. Lamotrigine was discontinued after lamotrigine allergy was diagnosed. The patient improved following a 9-day oral prednisone taper and was placed on oxcarbazepine 300 mg twice daily to manage their bipolar disorder. One day after completing the taper, the patient presented again with worsening rash, swelling, and cervical lymphadenopathy. Oxcarbazepine was discontinued, and oral prednisone 60 mg was reinstituted for an additional 11 days.

Dermatology evaluated the patient 10 days after completion of the second oral steroid taper (1 month after cessation of lamotrigine). The patient had erythroderma along with malaise, fevers, chills, and fatigue and a diffuse burning sensation (Figure 1). The patient was hypotensive and tachycardic with significant eosinophilia (42%; reference range, 0%-8%), transaminitis, and renal insufficiency. The patient was diagnosed with DIHS/DRESS based on their clinical presentation and calculated RegiSCAR score of 7 (score > 5 corresponds with definite DIHS/DRESS and points were given for fever, enlarged lymph nodes, eosinophilia ≥ 20%, skin rash extending > 50% of their body, edema and scaling, and 2 organs involved).2 A punch biopsy was confirmatory (Figure 2A).3 The patient was started on prednisone 80 mg once daily along with topical fluocinonide 0.05% ointment. However, the patient’s clinical status deteriorated, requiring hospital admission for heart failure evaluation. The echocardiogram revealed hyperdynamic circulation but was otherwise unremarkable.



The patient was maintained on prednisone 70 to 80 mg daily for 2 months before improvement of the rash and pruritus. The prednisone was slowly tapered over a 6-week period and then discontinued. Shortly after discontinuation, the patient redeveloped erythroderma. Skin biopsy and complete blood count (17.3% eosinophilia) confirmed the suspected DIHS/DRESS relapse (Figure 2B). In addition, the patient reported upper respiratory tract symptoms and concurrently tested positive for human herpesvirus 6 (HHV-6). The patient was restarted on prednisone and low-dose narrow-band UVB (nbUVB) therapy was added. Over the following 2 months, they responded well to low-dose nbUVB therapy. By the end of nbUVB treatment, about 5 months after initial presentation, the patient’s erythroderma improved, eosinophilia resolved, and they were able to tolerate prednisone taper. Ten months after cessation of lamotrigine, prednisone was finally discontinued. Two weeks later, the patient was screened for adrenal insufficiency (AI) given the prolonged steroid course. Their serum morning cortisol level was within normal limits.

Four months after DIHS/DRESS resolution and cessation of steroids, the patient noted significant patches of smooth alopecia on their posterior scalp and was diagnosed with alopecia areata. Treatment with intralesional triamcinolone over 2 months resulted in regrowth of hair (Figure 3). A month later, the patient reported increasing fatigue and anorexia. The patient was evaluated once more for AI, this time with low morning cortisol and low adrenocorticotrophic hormone (ACTH) levels—consistent with AI secondary to prolonged glucocorticoid therapy. The patient also was concomitantly evaluated for hypothyroidism with significantly elevated thyroperoxidase antibodies—confirming the diagnosis of Hashimoto thyroiditis.

Discussion

DIHS/DRESS syndrome is a rare, but potentially life-threatening hypersensitivity to a medication, often beginning 2 to 6 weeks after exposure to the causative agent. The incidence of DIHS/DRESS in the general population is about 2 per 100,000.3 Our patient presented with DIHS/DRESS 33 days after starting lamotrigine, which corresponds with the published mean onset of anticonvulsant-induced DIHS/DRESS (29.7-33.3 days).4 Recent evidence shows that time from drug exposure to DIHS/DRESS symptoms may vary by drug class, with antibiotics implicated as precipitating DIHS/DRESS in < 15 days.3 The diagnosis of DIHS/DRESS may be complicated for many reasons. The accompanying rash may be morbilliform, erythroderma, or exfoliative dermatitis with multiple anatomic regions affected.5 Systemic involvement with various internal organs occurs in > 90% of cases, with the liver and kidney involved most frequently.5 Overall mortality rate may be as high as 10% most commonly due to acute liver failure.5 Biopsy may be helpful in the diagnosis but is not always specific.5 Diagnostic criteria include RegiSCAR and J-SCAR scores; our patient met criteria for both (Table).5 

The pathogenesis of DIHS/DRESS remains unclear. Proposed mechanisms include genetic predisposition with human leukocyte antigen (HLA) haplotypes, autoimmune with a delayed cell-mediated immune response associated with herpesviruses, and abnormal enzymatic pathways that metabolize medications.2 Although no HLA has been identified between lamotrigine and DIHS, HLA-A*02:07 and HLA-B*15:02 have been associated with lamotrigine-induced cutaneous drug reactions in patients of Thai ancestry.6 Immunosuppression also is a risk factor, especially when accompanied by a primary or reactivated HHV-6 infection, as seen in our patient.2 Additionally, HHV-6 infection may be a common link between DIHS/DRESS and autoimmune thyroiditis but is believed to involve elevated levels of interferon-γ-induced protein-10 (IP-10) that may lead to excessive recruitment of cytotoxic T cells into target tissues.7 Elevated levels of IP-10 are seen in many autoimmune conditions, such as autoimmune thyroiditis, Sjögren syndrome, and Graves disease.8

 

 



DIHS/DRESS syndrome has been associated with development of autoimmune diseases as long-term sequelae. The most commonly affected organs are the thyroid and pancreas; approximately 4.8% of patients develop autoimmune thyroiditis and 3.5% develop fulminant T1DM.9 The time from onset of DIHS/DRESS to development of autoimmune thyroiditis can range from 2 months to 2 years, whereas the range from DIHS/DRESS onset to fulminant T1DM is about 40 days.9 Alopecia had been reported in 1, occurring 4 months after DIHS/DRESS onset. Our patient’s alopecia areata and Hashimoto thyroiditis occurred 14 and 15 months after DIHS/DRESS presentation, respectively.

Treatment

For management, early recognition and discontinuation of the offending agent is paramount. Systemic corticosteroids are the accepted treatment standard. Symptoms of DIHS/DRESS usually resolve between 3 and 18 weeks, with the mean resolution time at 7 weeks.10 Our patient developed a prolonged course with persistent eosinophilia for 20 weeks and cutaneous symptoms for 32 weeks—requiring 40 weeks of oral prednisone. The most significant clinical improvement occurred during the 8-week period low-dose nbUVB was used (Figure 4). There also are reports outlining the successful use of intravenous immunoglobulin, cyclosporine, cyclophosphamide, rituximab, or plasma exchange in cases refractory to oral corticosteroids.11

A recent retrospective case control study showed that treatment of DIHS/DRESS with cyclosporine in patients who had a contraindication to steroids resulted in faster resolution of symptoms, shorter treatment durations, and shorter hospitalizations than did those treated with corticosteroids.12 However, the data are limited by a significantly smaller number of patients treated with cyclosporine than steroids and the cyclosporine treatment group having milder cases of DIHS/DRESS.12

The risk of AI is increased for patients who have taken > 20 mg of prednisone daily ≥ 3 weeks, an evening dose ≥ 5 mg for a few weeks, or have a Cushingoid appearance.13 Patients may not regain full adrenal function for 12 to 18 months.14 Our patient had a normal basal serum cortisol level 2 weeks after prednisone cessation and then presented 5 months later with AI. While the reason for this period of normality is unclear, it may partly be due to the variable length of hypothalamic-pituitary-adrenal axis recovery time. Thus, ACTH stimulation tests in addition to serum cortisol may be done in patients with suspected AI for higher diagnostic certainty.10

Conclusions

DIHS/DRESS is a severe cutaneous adverse reaction that may require a prolonged treatment course until symptom resolution (40 weeks of oral prednisone in our patient). Oral corticosteroids are the mainstay of treatment, but long-term use is associated with significant adverse effects, such as AI in our patient. Alternative therapies, such as cyclosporine, look promising, but further studies are needed to determine safety profile and efficacy.12 Additionally, patients with DIHS/DRESS should be educated and followed for potential autoimmune sequelae; in our patient alopecia areata and autoimmune thyroiditis were late sequelae, occurring 14 and 15 months, respectively, after onset of DIHS/DRESS.

References

1. RegiSCAR. Accessed June 3, 2022. http://www.regiscar.org

2. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): an update in 2019. Allergol Int. 2019;68(3):301-308. doi:10.1016/j.alit.2019.03.006

3. Wolfson AR, Zhou L, Li Y, Phadke NA, Chow OA, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome identified in the electronic health record allergy module. J Allergy Clin Immunol Pract. 2019;7(2):633-640. doi:10.1016/j.jaip.2018.08.013

4. Sasidharanpillai S, Govindan A, Riyaz N, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis. Indian J Dermatol Venereol Leprol. 2016;82(1):28. doi:10.4103/0378-6323.168934

5. Kardaun SH, Sekula P, Valeyrie‐Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501

6. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00879

7. Yang C-W, Cho Y-T, Hsieh Y-C, Hsu S-H, Chen K-L, Chu C-Y. The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183(5):909-919. doi:10.1111/bjd.18942

8. Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res. 2014;46(9):597-602. doi:10.1055/s-0034-1382053

9. Kano Y, Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276-282. doi:10.1111/1346-8138.12770

10. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017

11. Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of psychotropic drug-induced dress syndrome: a systematic review. Mayo Clin Proc. 2016;91(6):787-801. doi:10.1016/j.mayocp.2016.03.006

12. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of cyclosporine for the treatment of DRESS syndrome. JAMA Dermatol. 2020;156(6):704-706. doi:10.1001/jamadermatol.2020.0048

13. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi:10.1016/j.semarthrit.2016.03.001

14. Jamilloux Y, Liozon E, Pugnet G, et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS ONE. 2013;8(7):e68713. doi:10.1371/journal.pone.0068713

References

1. RegiSCAR. Accessed June 3, 2022. http://www.regiscar.org

2. Shiohara T, Mizukawa Y. Drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): an update in 2019. Allergol Int. 2019;68(3):301-308. doi:10.1016/j.alit.2019.03.006

3. Wolfson AR, Zhou L, Li Y, Phadke NA, Chow OA, Blumenthal KG. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome identified in the electronic health record allergy module. J Allergy Clin Immunol Pract. 2019;7(2):633-640. doi:10.1016/j.jaip.2018.08.013

4. Sasidharanpillai S, Govindan A, Riyaz N, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a histopathology based analysis. Indian J Dermatol Venereol Leprol. 2016;82(1):28. doi:10.4103/0378-6323.168934

5. Kardaun SH, Sekula P, Valeyrie‐Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071-1080. doi:10.1111/bjd.12501

6. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00879

7. Yang C-W, Cho Y-T, Hsieh Y-C, Hsu S-H, Chen K-L, Chu C-Y. The interferon-γ-induced protein 10/CXCR3 axis is associated with human herpesvirus-6 reactivation and the development of sequelae in drug reaction with eosinophilia and systemic symptoms. Br J Dermatol. 2020;183(5):909-919. doi:10.1111/bjd.18942

8. Ruffilli I, Ferrari SM, Colaci M, Ferri C, Fallahi P, Antonelli A. IP-10 in autoimmune thyroiditis. Horm Metab Res. 2014;46(9):597-602. doi:10.1055/s-0034-1382053

9. Kano Y, Tohyama M, Aihara M, et al. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR). J Dermatol. 2015;42(3):276-282. doi:10.1111/1346-8138.12770

10. Cacoub P, Musette P, Descamps V, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588-597. doi:10.1016/j.amjmed.2011.01.017

11. Bommersbach TJ, Lapid MI, Leung JG, Cunningham JL, Rummans TA, Kung S. Management of psychotropic drug-induced dress syndrome: a systematic review. Mayo Clin Proc. 2016;91(6):787-801. doi:10.1016/j.mayocp.2016.03.006

12. Nguyen E, Yanes D, Imadojemu S, Kroshinsky D. Evaluation of cyclosporine for the treatment of DRESS syndrome. JAMA Dermatol. 2020;156(6):704-706. doi:10.1001/jamadermatol.2020.0048

13. Joseph RM, Hunter AL, Ray DW, Dixon WG. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review. Semin Arthritis Rheum. 2016;46(1):133-141. doi:10.1016/j.semarthrit.2016.03.001

14. Jamilloux Y, Liozon E, Pugnet G, et al. Recovery of adrenal function after long-term glucocorticoid therapy for giant cell arteritis: a cohort study. PLoS ONE. 2013;8(7):e68713. doi:10.1371/journal.pone.0068713

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Experts: EPA should assess risk of sunscreens’ UV filters

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The Environmental Protection Agency (EPA) should conduct an ecologic risk assessment of the UV filters found in sunscreens to understand their effects on aquatic environments and human health, an expert panel of the National Academies of Sciences, Engineering, and Medicine (NAS) said on Aug. 9.

The assessment is urgently needed, the experts said, and the results should be shared with the Food and Drug Administration, which oversees sunscreens.

mark wragg/iStockphoto.com

In its 400-page report, titled the Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health, the panel does not make recommendations but suggests that such an EPA risk assessment should highlight gaps in knowledge.

“We are teeing up the critical information that will be used to take on the challenge of risk assessment,” Charles A. Menzie, PhD, chair of the committee that wrote the report, said at a media briefing Aug. 9 when the report was released. Dr. Menzie is a principal at Exponent, Inc., an engineering and scientific consulting firm. He is former executive director of the Society of Environmental Toxicology and Chemistry.

The EPA sponsored the study, which was conducted by a committee of the National Academy of Sciences, a nonprofit, nongovernmental organization authorized by Congress that studies issues related to science, technology, and medicine.
 

Balancing aquatic, human health concerns

Such an EPA assessment, Dr. Menzie said in a statement, will help inform efforts to understand the environmental effects of UV filters as well as clarify a path forward for managing sunscreens. For years, concerns have been raised about the potential toxicity of sunscreens regarding many marine and freshwater aquatic organisms, especially coral. That concern, however, must be balanced against the benefits of sunscreens, which are known to protect against skin cancer. A low percentage of people use sunscreen regularly, Dr. Menzie and other panel members said.

“Only about a third of the U.S. population regularly uses sunscreen,” Mark Cullen, MD, vice chair of the NAS committee and former director of the Center for Population Health Sciences, Stanford (Calif.) University, said at the briefing. About 70% or 80% of people use it at the beach or outdoors, he said.
 

Report background, details

UV filters are the active ingredients in physical as well as chemical sunscreen products. They decrease the amount of UV radiation that reaches the skin. They have been found in water, sediments, and marine organisms, both saltwater and freshwater.

Currently, 17 UV filters are used in U.S. sunscreens; 15 of those are organic, such as oxybenzone and avobenzone, and are used in chemical sunscreens. They work by absorbing the rays before they damage the skin. In addition, two inorganic filters, which are used in physical sunscreens, sit on the skin and as a shield to block the rays.



UV filters enter bodies of water by direct release, as when sunscreens rinse off people while swimming or while engaging in other water activities. They also enter bodies of water in storm water runoff and wastewater.

Lab toxicity tests, which are the most widely used, provide effects data for ecologic risk assessment. The tests are more often used in the study of short-term, not long-term exposure. Test results have shown that in high enough concentrations, some UV filters can be toxic to algal, invertebrate, and fish species.

But much information is lacking, the experts said. Toxicity data for many species, for instance, are limited. There are few studies on the longer-term environmental effects of UV filter exposure. Not enough is known about the rate at which the filters degrade in the environment. The filters accumulate in higher amounts in different areas. Recreational water areas have higher concentrations.
 

The recommendations

The panel is urging the EPA to complete a formal risk assessment of the UV filters “with some urgency,” Dr. Cullen said. That will enable decisions to be made about the use of the products. The risks to aquatic life must be balanced against the need for sun protection to reduce skin cancer risk.

The experts made two recommendations:

  • The EPA should conduct ecologic risk assessments for all the UV filters now marketed and for all new ones. The assessment should evaluate the filters individually as well as the risk from co-occurring filters. The assessments should take into account the different exposure scenarios.
  • The EPA, along with partner agencies, and sunscreen and UV filter manufacturers should fund, support, and conduct research and share data. Research should include study of human health outcomes if usage and availability of sunscreens change.

Dermatologists should “continue to emphasize the importance of protection from UV radiation in every way that can be done,” Dr. Cullen said, including the use of sunscreen as well as other protective practices, such as wearing long sleeves and hats, seeking shade, and avoiding the sun during peak hours.
 

A dermatologist’s perspective

“I applaud their scientific curiosity to know one way or the other whether this is an issue,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC. “I welcome this investigation.”

Dr. Adam Friedman

The multitude of studies, Dr. Friedman said, don’t always agree about whether the filters pose dangers. He noted that the concentration of UV filters detected in water is often lower than the concentrations found to be harmful in a lab setting to marine life, specifically coral.

However, he said, “these studies are snapshots.” For that reason, calling for more assessment of risk is desirable, Dr. Friedman said, but “I want to be sure the call to do more research is not an admission of guilt. It’s very easy to vilify sunscreens – but the facts we know are that UV light causes skin cancer and aging, and sunscreen protects us against this.”

Dr. Friedman has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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The Environmental Protection Agency (EPA) should conduct an ecologic risk assessment of the UV filters found in sunscreens to understand their effects on aquatic environments and human health, an expert panel of the National Academies of Sciences, Engineering, and Medicine (NAS) said on Aug. 9.

The assessment is urgently needed, the experts said, and the results should be shared with the Food and Drug Administration, which oversees sunscreens.

mark wragg/iStockphoto.com

In its 400-page report, titled the Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health, the panel does not make recommendations but suggests that such an EPA risk assessment should highlight gaps in knowledge.

“We are teeing up the critical information that will be used to take on the challenge of risk assessment,” Charles A. Menzie, PhD, chair of the committee that wrote the report, said at a media briefing Aug. 9 when the report was released. Dr. Menzie is a principal at Exponent, Inc., an engineering and scientific consulting firm. He is former executive director of the Society of Environmental Toxicology and Chemistry.

The EPA sponsored the study, which was conducted by a committee of the National Academy of Sciences, a nonprofit, nongovernmental organization authorized by Congress that studies issues related to science, technology, and medicine.
 

Balancing aquatic, human health concerns

Such an EPA assessment, Dr. Menzie said in a statement, will help inform efforts to understand the environmental effects of UV filters as well as clarify a path forward for managing sunscreens. For years, concerns have been raised about the potential toxicity of sunscreens regarding many marine and freshwater aquatic organisms, especially coral. That concern, however, must be balanced against the benefits of sunscreens, which are known to protect against skin cancer. A low percentage of people use sunscreen regularly, Dr. Menzie and other panel members said.

“Only about a third of the U.S. population regularly uses sunscreen,” Mark Cullen, MD, vice chair of the NAS committee and former director of the Center for Population Health Sciences, Stanford (Calif.) University, said at the briefing. About 70% or 80% of people use it at the beach or outdoors, he said.
 

Report background, details

UV filters are the active ingredients in physical as well as chemical sunscreen products. They decrease the amount of UV radiation that reaches the skin. They have been found in water, sediments, and marine organisms, both saltwater and freshwater.

Currently, 17 UV filters are used in U.S. sunscreens; 15 of those are organic, such as oxybenzone and avobenzone, and are used in chemical sunscreens. They work by absorbing the rays before they damage the skin. In addition, two inorganic filters, which are used in physical sunscreens, sit on the skin and as a shield to block the rays.



UV filters enter bodies of water by direct release, as when sunscreens rinse off people while swimming or while engaging in other water activities. They also enter bodies of water in storm water runoff and wastewater.

Lab toxicity tests, which are the most widely used, provide effects data for ecologic risk assessment. The tests are more often used in the study of short-term, not long-term exposure. Test results have shown that in high enough concentrations, some UV filters can be toxic to algal, invertebrate, and fish species.

But much information is lacking, the experts said. Toxicity data for many species, for instance, are limited. There are few studies on the longer-term environmental effects of UV filter exposure. Not enough is known about the rate at which the filters degrade in the environment. The filters accumulate in higher amounts in different areas. Recreational water areas have higher concentrations.
 

The recommendations

The panel is urging the EPA to complete a formal risk assessment of the UV filters “with some urgency,” Dr. Cullen said. That will enable decisions to be made about the use of the products. The risks to aquatic life must be balanced against the need for sun protection to reduce skin cancer risk.

The experts made two recommendations:

  • The EPA should conduct ecologic risk assessments for all the UV filters now marketed and for all new ones. The assessment should evaluate the filters individually as well as the risk from co-occurring filters. The assessments should take into account the different exposure scenarios.
  • The EPA, along with partner agencies, and sunscreen and UV filter manufacturers should fund, support, and conduct research and share data. Research should include study of human health outcomes if usage and availability of sunscreens change.

Dermatologists should “continue to emphasize the importance of protection from UV radiation in every way that can be done,” Dr. Cullen said, including the use of sunscreen as well as other protective practices, such as wearing long sleeves and hats, seeking shade, and avoiding the sun during peak hours.
 

A dermatologist’s perspective

“I applaud their scientific curiosity to know one way or the other whether this is an issue,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC. “I welcome this investigation.”

Dr. Adam Friedman

The multitude of studies, Dr. Friedman said, don’t always agree about whether the filters pose dangers. He noted that the concentration of UV filters detected in water is often lower than the concentrations found to be harmful in a lab setting to marine life, specifically coral.

However, he said, “these studies are snapshots.” For that reason, calling for more assessment of risk is desirable, Dr. Friedman said, but “I want to be sure the call to do more research is not an admission of guilt. It’s very easy to vilify sunscreens – but the facts we know are that UV light causes skin cancer and aging, and sunscreen protects us against this.”

Dr. Friedman has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

 

The Environmental Protection Agency (EPA) should conduct an ecologic risk assessment of the UV filters found in sunscreens to understand their effects on aquatic environments and human health, an expert panel of the National Academies of Sciences, Engineering, and Medicine (NAS) said on Aug. 9.

The assessment is urgently needed, the experts said, and the results should be shared with the Food and Drug Administration, which oversees sunscreens.

mark wragg/iStockphoto.com

In its 400-page report, titled the Review of Fate, Exposure, and Effects of Sunscreens in Aquatic Environments and Implications for Sunscreen Usage and Human Health, the panel does not make recommendations but suggests that such an EPA risk assessment should highlight gaps in knowledge.

“We are teeing up the critical information that will be used to take on the challenge of risk assessment,” Charles A. Menzie, PhD, chair of the committee that wrote the report, said at a media briefing Aug. 9 when the report was released. Dr. Menzie is a principal at Exponent, Inc., an engineering and scientific consulting firm. He is former executive director of the Society of Environmental Toxicology and Chemistry.

The EPA sponsored the study, which was conducted by a committee of the National Academy of Sciences, a nonprofit, nongovernmental organization authorized by Congress that studies issues related to science, technology, and medicine.
 

Balancing aquatic, human health concerns

Such an EPA assessment, Dr. Menzie said in a statement, will help inform efforts to understand the environmental effects of UV filters as well as clarify a path forward for managing sunscreens. For years, concerns have been raised about the potential toxicity of sunscreens regarding many marine and freshwater aquatic organisms, especially coral. That concern, however, must be balanced against the benefits of sunscreens, which are known to protect against skin cancer. A low percentage of people use sunscreen regularly, Dr. Menzie and other panel members said.

“Only about a third of the U.S. population regularly uses sunscreen,” Mark Cullen, MD, vice chair of the NAS committee and former director of the Center for Population Health Sciences, Stanford (Calif.) University, said at the briefing. About 70% or 80% of people use it at the beach or outdoors, he said.
 

Report background, details

UV filters are the active ingredients in physical as well as chemical sunscreen products. They decrease the amount of UV radiation that reaches the skin. They have been found in water, sediments, and marine organisms, both saltwater and freshwater.

Currently, 17 UV filters are used in U.S. sunscreens; 15 of those are organic, such as oxybenzone and avobenzone, and are used in chemical sunscreens. They work by absorbing the rays before they damage the skin. In addition, two inorganic filters, which are used in physical sunscreens, sit on the skin and as a shield to block the rays.



UV filters enter bodies of water by direct release, as when sunscreens rinse off people while swimming or while engaging in other water activities. They also enter bodies of water in storm water runoff and wastewater.

Lab toxicity tests, which are the most widely used, provide effects data for ecologic risk assessment. The tests are more often used in the study of short-term, not long-term exposure. Test results have shown that in high enough concentrations, some UV filters can be toxic to algal, invertebrate, and fish species.

But much information is lacking, the experts said. Toxicity data for many species, for instance, are limited. There are few studies on the longer-term environmental effects of UV filter exposure. Not enough is known about the rate at which the filters degrade in the environment. The filters accumulate in higher amounts in different areas. Recreational water areas have higher concentrations.
 

The recommendations

The panel is urging the EPA to complete a formal risk assessment of the UV filters “with some urgency,” Dr. Cullen said. That will enable decisions to be made about the use of the products. The risks to aquatic life must be balanced against the need for sun protection to reduce skin cancer risk.

The experts made two recommendations:

  • The EPA should conduct ecologic risk assessments for all the UV filters now marketed and for all new ones. The assessment should evaluate the filters individually as well as the risk from co-occurring filters. The assessments should take into account the different exposure scenarios.
  • The EPA, along with partner agencies, and sunscreen and UV filter manufacturers should fund, support, and conduct research and share data. Research should include study of human health outcomes if usage and availability of sunscreens change.

Dermatologists should “continue to emphasize the importance of protection from UV radiation in every way that can be done,” Dr. Cullen said, including the use of sunscreen as well as other protective practices, such as wearing long sleeves and hats, seeking shade, and avoiding the sun during peak hours.
 

A dermatologist’s perspective

“I applaud their scientific curiosity to know one way or the other whether this is an issue,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC. “I welcome this investigation.”

Dr. Adam Friedman

The multitude of studies, Dr. Friedman said, don’t always agree about whether the filters pose dangers. He noted that the concentration of UV filters detected in water is often lower than the concentrations found to be harmful in a lab setting to marine life, specifically coral.

However, he said, “these studies are snapshots.” For that reason, calling for more assessment of risk is desirable, Dr. Friedman said, but “I want to be sure the call to do more research is not an admission of guilt. It’s very easy to vilify sunscreens – but the facts we know are that UV light causes skin cancer and aging, and sunscreen protects us against this.”

Dr. Friedman has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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Federal Health Care Data Trends 2022

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Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

 

In this issue:

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

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Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

 

In this issue:

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner highlighting the latest research and study outcomes related to the health of veteran and active-duty populations. 

 

In this issue:

Federal Practitioner would like to thank the following experts for their review of content and helpful guidance in developing this issue: 

Kelvin N.V. Bush, MD, FACC, CCDS; Sonya Borrero, MD, MS; Kenneth L. Cameron, PhD, MPH, ATC, FNATA; Jason DeViva, PhD; Ellen Lockard Edens, MD; Leonard E. Egede, MD, MS; Amy Justice, MD, PhD; Stephanie Knudson, MD; Willis H. Lyford, MD; Sarah O. Meadows, PhD; Tamara Schult, PhD, MPH; Eric L. Singman, MD, PhD; Art Wallace, MD, PhD; Elizabeth Waterhouse, MD, FAAN

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Does hidradenitis suppurativa worsen during pregnancy?

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PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.

In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.

“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.

Dr. Jennifer Hsiao


“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.

During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.

She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.

“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”

To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.

“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”

Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.

As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.

Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.

“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.

Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.

“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”

As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.

“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”

Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.



“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”

To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.

Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.

“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”

Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”

In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.

“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbookA Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).

Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”

In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.

HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.

After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.

A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”

Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.

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PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.

In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.

“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.

Dr. Jennifer Hsiao


“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.

During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.

She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.

“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”

To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.

“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”

Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.

As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.

Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.

“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.

Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.

“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”

As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.

“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”

Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.



“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”

To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.

Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.

“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”

Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”

In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.

“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbookA Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).

Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”

In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.

HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.

After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.

A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”

Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.

PORTLAND, ORE. – The recurrent boils, abscesses, and nodules of the chronic inflammatory skin condition hidradenitis suppurativa (HS) may improve during pregnancy for a subset of women, but for many, pregnancy does not change the disease course and may worsen symptoms.

In addition, HS appears to be a risk factor for adverse pregnancy and maternal outcomes.

“This is relevant, because in the United States, HS disproportionately impacts women compared with men by a ratio of about 3:1,” Jennifer Hsiao, MD, said at the annual meeting of the Pacific Dermatologic Association.

Dr. Jennifer Hsiao


“Also, the highest prevalence of HS is among people in their 20s and 30s, so in their practice, clinicians will encounter female patients with HS who are either pregnant or actively thinking about getting pregnant,” she said.

During a wide-ranging presentation, Dr. Hsiao of the department of dermatology at the University of Southern California, Los Angeles, described the impact of pregnancy on HS, identified appropriate treatment options for this population of patients, and discussed HS comorbidities that may be exacerbated during pregnancy.

She began by noting that levels of progesterone and estrogen both rise during pregnancy. Progesterone is known to suppress development and function of Th1 and Th17 T cells, but the effect of estrogen on inflammation is less well known. At the same time, serum levels of interleukin (IL)-1 receptor antagonist and soluble TNF-alpha receptor both increase during pregnancy.

“This would lead to serum IL-1 and TNF-alpha falling, sort of like the way that we give anti–IL-1 and TNF blockers as HS treatments,” she explained. “So, presumably that might be helpful during HS in pregnancy. On the flip side, pregnancy weight gain can exacerbate HS, with increased friction between skin folds. In addition, just having more adipocytes can promote secretion of proinflammatory cytokines like TNF-alpha.”

To better understand the effect of pregnancy on patients with HS, Dr. Hsiao and colleagues conducted a systematic review and meta-analysis on the topic published in Dermatology. They included eight studies in which a total of 672 patients self-reported their HS disease course during pregnancy and 164 self-reported whether they had a postpartum HS flare or not. On pooled analyses, HS improved in 24% of patients but worsened in 20%. In addition, 60% of patients experienced a postpartum flare.

“So, at this point in time, based on the literature, it would be fair to tell your patient that during pregnancy, HS has a mixed response,” Dr. Hsiao said. “About 25% may have improvement, but for the rest, HS symptoms may be unchanged or even worsen. That’s why it’s so important to be in contact with your pregnant patients, because not only may they have to stay on treatment, but they might also have to escalate [their treatment] during pregnancy.”

Lifestyle modifications to discuss with pregnant HS patients include appropriate weight gain during pregnancy, smoking cessation, and avoidance of tight-fitting clothing, “since friction can make things worse,” she said. Topical antibiotics safe to use during pregnancy for patients with mild HS include clindamycin 1%, erythromycin 2%, and metronidazole 0.75% applied twice per day to active lesions, she continued.

As for systemic therapies, some data exist to support the use of metformin 500 mg once daily, titrating up to twice or – if needed and tolerated – three times daily for patients with mild to moderate HS, she said, referencing a paper published in the Journal of the European Academy of Dermatology and Venereology.

Zinc gluconate is another potential option. Of 22 nonpregnant HS patients with Hurley stage I-II disease who were treated with zinc gluconate 90 mg daily, 8 had a complete remission of HS and 14 had partial remission, according to a report in Dermatology.

“Zinc supplementation of up to 50 mg daily has shown no effect on neonatal or maternal outcomes at birth based on existing medical literature,” Dr. Hsiao added.

Among antibiotics, injections of intralesional Kenalog 5-10 mg/mL have been shown to decrease pain and inflammation in acute HS lesions and are unlikely to pose significant risks during pregnancy, but a course of systemic antibiotics may be warranted in moderate to severe disease, she said. These include, but are not limited to, clindamycin, erythromycin base, cephalexin, or metronidazole.

“In addition, some of my HS colleagues and I will also use other antibiotics such as Augmentin [amoxicillin/clavulanate] or cefdinir for HS and these are also generally considered safe to use in pregnancy,” she said. “Caution is advised with using rifampin, dapsone, and moxifloxacin during pregnancy.”

As for biologic agents, the first-line option is adalimumab, which is currently the only Food and Drug Administration–approved treatment for HS.

“There is also good efficacy data for infliximab,” she said. “Etanercept has less placental transfer than adalimumab or infliximab so it’s safer to use in pregnancy, but it has inconsistent data for efficacy in HS, so I would generally avoid using it to treat HS and reach for adalimumab or infliximab instead.”

Data on TNF-alpha inhibitors from the GI and rheumatology literature have demonstrated that there is minimal placental transport of maternal antibodies during the first two trimesters of pregnancy.



“It’s at the beginning of the third trimester that the placental transfer of antibodies picks up,” she said. “At that point in time, you can have a discussion with the patient: do you want to stay on treatment and treat through, or do you want to consider being taken off the medication? I think this is a discussion that needs to be had, because let’s say you peel off adalimumab or infliximab and they have severe HS flares. I’m not sure that leads to a better outcome. I usually treat through for my pregnant patients.”

To better understand clinician practice patterns on the management of HS in pregnancy, Dr. Hsiao and Erin Collier, MD, MPH, of University of California, Los Angeles, and colleagues distributed an online survey to HS specialists in North America. They reported the findings in the International Journal of Women’s Dermatology.

Of the 49 respondents, 36 (73%) directed an HS specialty clinic and 29 (59%) reported having prescribed or continued a biologic agent in a pregnant HS patient. The top three biologics prescribed were adalimumab (90%), infliximab (41%), and certolizumab pegol (34%). Dr. Hsiao noted that certolizumab pegol is a pegylated anti-TNF, so it lacks an Fc region on the medication.

“This means that it cannot be actively transported by the neonatal Fc receptor on the placenta, thus resulting in minimal placental transmission,” she said. “The main issue is that there is little data on its efficacy in HS, but it’s a reasonable option to consider in a pregnant patient, especially in a patient with severe HS who asks, ‘what’s the safest biologic that I can go on?’ But you’d have to discuss with the patient that in terms of efficacy data, there is much less in the literature compared to adalimumab or infliximab.”

Breastfeeding while on anti–TNF-alpha biologics is considered safe. “There are minimal amounts of medication in breast milk,” she said. “If any gets through, infant gastric digestion is thought to take care of the rest. Of note, babies born to mothers who are continually treated with biologic agents should not be given live vaccinations for 6 months after birth.”

In a single-center study, Dr. Hsiao and colleagues retrospectively examined pregnancy complications, pregnancy outcomes, and neonatal outcomes in patients with HS. The study population included 202 pregnancies in 127 HS patients. Of 134 babies born to mothers with HS, 74% were breastfed and 24% were bottle-fed, and presence of HS lesions on the breast was significantly associated with not breastfeeding.

“So, when we see these patients, if moms decide to breastfeed and they have lesions on the breast, it would be helpful to discuss expectations and perhaps treat HS breast lesions early, so the breastfeeding process may go more smoothly for them after they deliver,” said Dr. Hsiao, who is one of the editors of the textbookA Comprehensive Guide to Hidradenitis Suppurativa” (Elsevier, 2021). Safety-related resources that she recommends for clinicians include Mother to Baby and the Drugs and Lactation Database (LactMed).

Dr. Hsiao concluded her presentation by spotlighting the influence of pregnancy on HS comorbidities. Patients with HS already have a higher prevalence of depression and anxiety compared to controls. “Pregnancy can exacerbate underlying mood disorders in patients,” she said. “That’s why monitoring the patient’s mood and coordinating mental health care with the patient’s primary care physician and ob.gyn. is important.”

In addition, pregnancy-related changes in body mass index, blood pressure, lipid metabolism, and glucose tolerance trend toward changes seen in metabolic syndrome, she said, and HS patients are already at higher risk of metabolic syndrome compared with the general population.

HS may also compromise a patient’s ability to have a healthy pregnancy. Dr. Hsiao worked with Amit Garg, MD, and colleagues on a study that drew from the IBM MarketScan Commercial Claims Database to evaluate adverse pregnancy and maternal outcomes in women with HS between Jan. 1, 2011, and Sept. 30, 2015.

After the researchers adjusted for age, race, smoking status, and other comorbidities, they found that HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20), gestational diabetes (OR, 1.26), and cesarean section (OR, 1.09). The findings were published in the Journal of the American Academy of Dermatology.

A separate study that used the same database found comparable results, also published in the Journal of the American Academy of Dermatology. “What I say to patients right now is, ‘there are many women with HS who have healthy pregnancies and deliver healthy babies, but HS could be a risk factor for a higher-risk pregnancy.’ It’s important that these patients are established with an ob.gyn. and are closely monitored to make sure that we optimize their care and give them the best outcome possible for mom and baby.”

Dr. Hsiao disclosed that she is on the board of directors for the Hidradenitis Suppurativa Foundation. She has also served as an advisor for Novartis, UCB, and Boehringer Ingelheim and as a speaker and advisor for AbbVie.

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Popliteal plaques

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Popliteal plaques

Both a Wood lamp examination and a potassium hydroxide (KOH) prep returned negative results. Those findings, combined with the patient’s month-long antifungal medication adherence, helped to rule out other diagnoses. Based on history and examination, the patient was diagnosed with erythrasma.

Erythrasma is a skin infection caused by the gram-positive bacteria Corynebacterium minutissimum1 that usually manifests in moist intertriginous areas. Sometimes it is secondary to fungal or yeast infections, local skin irritation due to friction, or due to maceration of the skin from persistent moisture. The Wood lamp examination can show coral-red fluorescence in erythrasma, but recent bathing (as in this case) may limit this finding.1

The differential diagnosis of erythematous plaques in an intertriginous area includes inverse psoriasis. However, this patient had no nail changes, joint difficulties, or other rashes consistent with psoriasis. Macerated, erythematous inflammatory changes in intertriginous areas are always concerning for fungal infections (eg, yeast infection, tinea corporis), especially with the presence of any scale. In this case, the patient’s medication regimen helped to rule out these types of conditions.

First-line therapy for erythrasma includes topical antibiotics: clindamycin, erythromycin, mupirocin, and fusidic acid. Systemic antibiotics in the tetracycline family and macrolides may also be used but have a higher risk of adverse effects. Keeping the affected area dry is a useful adjunct to pharmacologic therapy.

The patient was treated with topical clindamycin bid for 7 days. By her 2-month follow-up appointment, there were no residual skin changes. Had the plaques persisted, the possibility of inverse psoriasis would have been revisited, with either presumptive treatment prescribed or biopsy performed to establish the diagnosis.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733

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Popliteal plaques

Both a Wood lamp examination and a potassium hydroxide (KOH) prep returned negative results. Those findings, combined with the patient’s month-long antifungal medication adherence, helped to rule out other diagnoses. Based on history and examination, the patient was diagnosed with erythrasma.

Erythrasma is a skin infection caused by the gram-positive bacteria Corynebacterium minutissimum1 that usually manifests in moist intertriginous areas. Sometimes it is secondary to fungal or yeast infections, local skin irritation due to friction, or due to maceration of the skin from persistent moisture. The Wood lamp examination can show coral-red fluorescence in erythrasma, but recent bathing (as in this case) may limit this finding.1

The differential diagnosis of erythematous plaques in an intertriginous area includes inverse psoriasis. However, this patient had no nail changes, joint difficulties, or other rashes consistent with psoriasis. Macerated, erythematous inflammatory changes in intertriginous areas are always concerning for fungal infections (eg, yeast infection, tinea corporis), especially with the presence of any scale. In this case, the patient’s medication regimen helped to rule out these types of conditions.

First-line therapy for erythrasma includes topical antibiotics: clindamycin, erythromycin, mupirocin, and fusidic acid. Systemic antibiotics in the tetracycline family and macrolides may also be used but have a higher risk of adverse effects. Keeping the affected area dry is a useful adjunct to pharmacologic therapy.

The patient was treated with topical clindamycin bid for 7 days. By her 2-month follow-up appointment, there were no residual skin changes. Had the plaques persisted, the possibility of inverse psoriasis would have been revisited, with either presumptive treatment prescribed or biopsy performed to establish the diagnosis.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Popliteal plaques

Both a Wood lamp examination and a potassium hydroxide (KOH) prep returned negative results. Those findings, combined with the patient’s month-long antifungal medication adherence, helped to rule out other diagnoses. Based on history and examination, the patient was diagnosed with erythrasma.

Erythrasma is a skin infection caused by the gram-positive bacteria Corynebacterium minutissimum1 that usually manifests in moist intertriginous areas. Sometimes it is secondary to fungal or yeast infections, local skin irritation due to friction, or due to maceration of the skin from persistent moisture. The Wood lamp examination can show coral-red fluorescence in erythrasma, but recent bathing (as in this case) may limit this finding.1

The differential diagnosis of erythematous plaques in an intertriginous area includes inverse psoriasis. However, this patient had no nail changes, joint difficulties, or other rashes consistent with psoriasis. Macerated, erythematous inflammatory changes in intertriginous areas are always concerning for fungal infections (eg, yeast infection, tinea corporis), especially with the presence of any scale. In this case, the patient’s medication regimen helped to rule out these types of conditions.

First-line therapy for erythrasma includes topical antibiotics: clindamycin, erythromycin, mupirocin, and fusidic acid. Systemic antibiotics in the tetracycline family and macrolides may also be used but have a higher risk of adverse effects. Keeping the affected area dry is a useful adjunct to pharmacologic therapy.

The patient was treated with topical clindamycin bid for 7 days. By her 2-month follow-up appointment, there were no residual skin changes. Had the plaques persisted, the possibility of inverse psoriasis would have been revisited, with either presumptive treatment prescribed or biopsy performed to establish the diagnosis.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733

References

1. Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733

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In one state, pandemic tamped down lice and scabies cases

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The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.



Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

 

 

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

The study received no outside funding. The researchers and Dr. Maguiness had no financial conflicts to disclose.

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The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.



Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

 

 

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

The study received no outside funding. The researchers and Dr. Maguiness had no financial conflicts to disclose.

The incidence of lice and scabies decreased significantly among children and adults in North Carolina during the confinement period of the COVID-19 pandemic, between March 2020 and February 2021, according to a report in Pediatric Dermatology.

When COVID-19 was declared a public health emergency by the World Health Organization in March 2020, many countries including the United States enacted lockdown and isolation measures to help contain the spread of the disease. Since scabies and lice are both spread by direct contact, “we hypothesized that the nationwide lockdown would influence the transmission of these two conditions among individuals,” wrote Marianne Bonanno, MD, of the University of North Carolina, Chapel Hill, and colleagues.

“The pandemic created a unique opportunity for real-life observations following physical distancing measures being put in place,” coauthor Christopher Sayed, MD, associate professor of dermatology at UNC, said in an interview. “It makes intuitive sense that since lice and scabies spread by cost physical contact that rates would decrease with school closures and other physical distancing measures. Reports from other countries in which extended families more often live together and were forced to spend more time in close quarters saw increased rates so it was interesting to see this contrast,” he noted.

In the study, the researchers reviewed data from 1,858 cases of adult scabies, 893 cases of pediatric scabies, and 804 cases of pediatric lice reported in North Carolina between March 2017 and February 2021. They compared monthly cases of scabies and lice, and prescriptions during the period before the pandemic (March 2017 to February 2020), and during the pandemic (March 2020 to February 2021).

Pediatric lice cases decreased by 60.6% over the study period (P < .001). Significant decreases also occurred in adult scabies (31.1%, P < .001) and pediatric scabies (39%, P < .01).

The number of prescriptions for lice and scabies also decreased significantly (P < .01) during the study period, although these numbers differed from the actual cases. Prescriptions decreased by 41.4%, 29.9%, and 69.3% for pediatric scabies, adult scabies, and pediatric lice, respectively.



Both pediatric scabies and pediatric lice showed a greater drop in prescriptions than in cases, while the drop in prescriptions for adult scabies was slightly less than the drop in cases.

The difference in the decreased numbers between cases and prescriptions may stem from the decrease in close contacts during the pandemic, which decreased the need for multiple prescriptions, but other potential explanations could be examined in future studies, the researchers wrote in their discussion.

The study findings were limited by several factors including the cross-sectional design and potential underdiagnosis and underreporting, as well as the focus only on a population in a single state, which may limit generalizability, the researchers noted.

However, the results offer preliminary insights on the impact of COVID-19 restrictions on scabies and lice, and suggest the potential value of physical distancing to reduce transmission of both conditions, especially in settings such as schools and prisons, to help contain future outbreaks, they concluded.

The study findings reinforce physical contact as the likely route of disease transmission, for lice and scabies, Dr. Sayed said in the interview. “It’s possible distancing measures on a small scale could be considered for outbreaks in institutional settings, though the risks of these infestations are much lower than with COVID-19,” he said. “It will be interesting to observe trends as physical distancing measures end to see if cases rebound in the next few years,” he added.

 

 

Drop in cases likely temporary

“Examining the epidemiology of different infectious diseases over time is an interesting and important area of study,” said Sheilagh Maguiness, MD, associate professor of dermatology and pediatrics at the University of Minnesota, Minneapolis, who was asked to comment on the results.

“The pandemic dramatically altered the daily lives of adults and children across the globe, and we can learn a lot from studying how social distancing and prolonged masking has made an impact on the incidence and prevalence of different infectious illnesses in the country and across the world,” she said in an interview.

Dr. Maguiness said she was not surprised by the study findings. “In fact, other countries have published similar studies documenting a reduction in both head lice and scabies infestations during the time of the pandemic,” she said. “In France, it was noted that during March to December 2020, there was a reduction in sales for topical head lice and scabies treatments of 44% and 14%, respectively. Similarly, a study from Argentina documented a decline in head lice infestations by about 25% among children,” she said.

“I personally noted a marked decrease in both of these diagnoses among children in my own clinic,” she added.

“Since both of these conditions are spread through close physical contact with others, it makes sense that there would be a steep decline in ectoparasitic infections during times of social distancing. However, anecdotally we are now diagnosing and treating these infestations again more regularly in our clinic,” said Dr. Maguiness. “As social distancing relaxes, I would expect that the incidence of both head lice and scabies will again increase.” 

The study received no outside funding. The researchers and Dr. Maguiness had no financial conflicts to disclose.

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FDA acts against sales of unapproved mole and skin tag products on Amazon, other sites

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The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

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The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

The Food and Drug Administration has sent warning letters to three companies, including Amazon, for selling mole and skin tag removal products that have not been approved by the agency, according to a press release issued on Aug. 9.

In addition to Amazon.com, the other two companies are Ariella Naturals, and Justified Laboratories.

Currently, no over-the-counter products are FDA-approved for the at-home removal of moles and skin tags, and use of unapproved products could be dangerous to consumers, according to the statement. These products may be sold as ointments, gels, sticks, or liquids, and may contain high concentrations of salicylic acid or other harmful ingredients. Introducing unapproved products in to interstate commerce violates the Federal Food, Drug, and Cosmetic Act.

Two products sold on Amazon are the “Deisana Skin Tag Remover, Mole Remover and Repair Gel Set” and “Skincell Mole Skin Tag Corrector Serum,” according to the letter sent to Amazon.

The warning letters alert the three companies that they have 15 days from receipt to address any violations. However, warning letters are not a final FDA action, according to the statement.

“The agency’s rigorous surveillance works to identify threats to public health and stop these products from reaching our communities,” Donald D. Ashley, JD, director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research, said in the press release. “This includes where online retailers like Amazon are involved in the interstate sale of unapproved drug products. We will continue to work diligently to ensure that online retailers do not sell products that violate federal law,” he added.

The statement emphasized that moles should be evaluated by a health care professional, as attempts at self-diagnosis and at-home treatment could lead to a delayed cancer diagnosis, and potentially to cancer progression.

Products marketed to consumers for at-home removal of moles, skin tags, and other skin lesions could cause injuries, infections, and scarring, according to a related consumer update first posted by the FDA in June, which was updated after the warning letters were sent out.

Consumers and health care professionals are encouraged to report any adverse events related to mole removal or skin tag removal products to the agency’s MedWatch Adverse Event Reporting program.

The FDA also offers an online guide, BeSafeRx, with advice for consumers about potential risks of using online pharmacies and how to do so safely.

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Topical ruxolitinib quickly relieves atopic dermatitis itch in Black patients

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Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

  • Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
  • At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
  • At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
  • Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.
 

 

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

A version of this article first appeared on Medscape.com.

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Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

  • Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
  • At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
  • At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
  • Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.
 

 

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

A version of this article first appeared on Medscape.com.

Topical ruxolitinib appears to quickly relieve itch in Black patients with atopic dermatitis (AD), an industry-sponsored analysis of pooled data from two studies suggests.

“Ruxolitinib cream monotherapy over 8 weeks was associated with rapid and considerable itch relief in Black or African American patients with AD and was well tolerated,” the study authors wrote in a poster presented at the annual meeting of the Society for Investigative Dermatology.

AD can behave differently in different racial groups and can be especially bothersome in Black patients. AD has a prevalence of about 20% in Black children and 5%-10% in Black adults. Black children are roughly twice as likely to be diagnosed with AD, and to have severe AD, than White children, according to the authors.

Lead author Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, and colleagues used pooled data from two identically designed phase 3 studies to describe the effects of the cream formulation of the Janus kinase (JAK) 1 and JAK 2 inhibitor ruxolitinib on itch in Black patients.

Topical ruxolitinib (Opzelura), 1.5%, was approved last September for treating AD in non-immunocompromised patients with mild to moderate AD, ages 12 years and older. In July 2022, it was approved for the treatment of nonsegmental vitiligo in the same age group.  

FDA approval for AD was based on the results of the TRuE-AD1 and TRuE-AD2 double-blind randomized trials, which enrolled about 1,200 patients over age 12 with AD. These patients included 292 Black teenagers and adults between aged 12-71 years who had AD for 2 years or longer, with an Investigator’s Global Assessment (IGA) score of 2 or 3, with 3%-20% affected body surface area, excluding the scalp.

Of the 292 patients, those in the two treatment groups (n = 231) applied ruxolitinib cream twice a day for 8 weeks (0.75% in 118 patients and 1.5% in 113 patients) and 61 applied the vehicle. They used electronic diaries to record the worst level of itch they had experienced each day, from 0 (no itch) to 10 (worst imaginable itch). The main results were as follows: 

  • Mean itch numerical rating scale (NRS) scores at baseline were 5.3 and 5.4 for ruxolitinib cream 0.75% and 1.5%, respectively, and 5.7 for vehicle. Within about 12 hours of first application, mean itch NRS scores dropped –0.6 and –0.7 from baseline among those treated with ruxolitinib cream 0.75% and 1.5%, respectively, compared with –0.2 for those on the vehicle. At day 4, the decreases were –1.4 and –1.6 for ruxolitinib cream 0.75% and 1.5%, respectively, versus –0.6 for the vehicle (P = .026 and P = .005, respectively, vs. vehicle).
  • At day 2, among the 187 patients with a baseline itch NRS score 4 or higher, more patients achieved 4-point or greater itch NRS improvement: 6.1% and 16.4% for ruxolitinib cream 0.75% and 1.5%, respectively versus 0% for vehicle. At day 7, the differences were 15.9% and 26.6% versus 3%, respectively. And by week 8, they increased to 30.1% and 43.2% versus 17.5% (P = .212 and P = .009), respectively.
  • At week 2, 19% of patients in the 0.75% formulation group and 19.4% of patients in the 1.5% formulation group, compared with 5.3% in the vehicle group, reported no days of itch on question 1 of the Patient-Oriented Eczema Measure (POEM) questionnaire that evaluated various aspects of the disease over the previous week. By week 8, the differences grew to 34% and 30.8% versus 12.2%, respectively.
  • Adverse events, reported by 14.4% and 22.1% of patients on 0.75% and 1.5% ruxolitinib, respectively, and by 32.8% of patients who received the vehicle, were headaches, upper respiratory tract infection, and application site pain.
 

 

Ruxolitinib may be an alternative to systemic immunosuppressives

Asked to comment on the results, Amy J. McMichael, MD, professor of dermatology at Wake Forest University School of Medicine, Winston-Salem, N.C., called itch “one of the major life disruptors in atopic dermatitis.”

Providers often assume that patients of different races respond similarly to treatment, but that is not always true, she noted in an email.

“This study proves ruxolitinib’s effectiveness in Black patients, who often have more severe atopic dermatitis signs and symptoms,” said Dr. McMichael, who was not involved in the study. “The fact that atopic dermatitis in patients of color has been singled out to examine efficacy is a great way to show that the findings are not just in those who have thinner plaques and potentially less longstanding thickening of the skin from scratching (lichenification),” she added.

Dr. McMichael welcomed the lack of systemic side effects and quick relief of itch with this treatment, noting that the effect on itch “is rare with other treatments and extremely rare with other topical medications.”

The effect of topical ruxolitinib on pruritus “was interesting and surprising because very few available topical medications can control itch,” she explained. “The strongest topical steroids can help with pruritus, but they have the risk for skin thinning (atrophy),” while topical ruxolitinib is not associated with skin atrophy.

“After topical steroids fail as first-line treatment, it is likely that more patients will be given this topical medication rather than be moved to immunosuppressive systemic medications,” she noted.

All study authors report relevant relationships with Incyte Corporation, which manufactures ruxolitinib and funded the study, and several authors report employment and shareholding interests in the company. Dr. McMichael reports no relevant relationship with the study.

A version of this article first appeared on Medscape.com.

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Linear leg rash

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A 4-mm punch biopsy confirmed that this was a case of blaschkitis. This uncommon condition is referred to as adult blaschkitis because it resembles lichen striatus, a linear erythematous papular eruption usually seen in children younger than 15 years of age that erupts along Blaschko lines. The biopsy in this case helped to rule out lichen planus, which can also manifest with an erythematous papular eruption along Blaschko lines.

Adult blaschkitis is thought to be a hypersensitivity reaction involving T cells. It has been linked to medication use, insect stings, trauma, and autoimmune disease.1 The characteristic linear pattern is due to the inflammatory response following the Blaschko lines of keratinocytes that migrated during the embryonic phase.1 Post-inflammatory hyperpigmentation is a frequent complication. Topical steroids often help with the itching, but do not usually make the lesions go away. There have been better results in reducing itching and lesion prominence with intralesional steroid injections, topical calcipotriol, or calcineurin inhibitors.1 The inflammation usually spontaneously resolves over 3 to 12 months.

The patient was advised that the condition is benign and would likely resolve on its own over time. She was counseled that since the clobetasol was helping with her itching, she could use it (sparingly) as needed. She was cautioned that prolonged usage could lead to skin atrophy.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Al-Balbeesi A. Adult blaschkitis with lichenoid features and blood eosinophilia. Cureus. 2021;13:e16846. doi: 10.7759/cureus.16846

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Linear leg rash

A 4-mm punch biopsy confirmed that this was a case of blaschkitis. This uncommon condition is referred to as adult blaschkitis because it resembles lichen striatus, a linear erythematous papular eruption usually seen in children younger than 15 years of age that erupts along Blaschko lines. The biopsy in this case helped to rule out lichen planus, which can also manifest with an erythematous papular eruption along Blaschko lines.

Adult blaschkitis is thought to be a hypersensitivity reaction involving T cells. It has been linked to medication use, insect stings, trauma, and autoimmune disease.1 The characteristic linear pattern is due to the inflammatory response following the Blaschko lines of keratinocytes that migrated during the embryonic phase.1 Post-inflammatory hyperpigmentation is a frequent complication. Topical steroids often help with the itching, but do not usually make the lesions go away. There have been better results in reducing itching and lesion prominence with intralesional steroid injections, topical calcipotriol, or calcineurin inhibitors.1 The inflammation usually spontaneously resolves over 3 to 12 months.

The patient was advised that the condition is benign and would likely resolve on its own over time. She was counseled that since the clobetasol was helping with her itching, she could use it (sparingly) as needed. She was cautioned that prolonged usage could lead to skin atrophy.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Linear leg rash

A 4-mm punch biopsy confirmed that this was a case of blaschkitis. This uncommon condition is referred to as adult blaschkitis because it resembles lichen striatus, a linear erythematous papular eruption usually seen in children younger than 15 years of age that erupts along Blaschko lines. The biopsy in this case helped to rule out lichen planus, which can also manifest with an erythematous papular eruption along Blaschko lines.

Adult blaschkitis is thought to be a hypersensitivity reaction involving T cells. It has been linked to medication use, insect stings, trauma, and autoimmune disease.1 The characteristic linear pattern is due to the inflammatory response following the Blaschko lines of keratinocytes that migrated during the embryonic phase.1 Post-inflammatory hyperpigmentation is a frequent complication. Topical steroids often help with the itching, but do not usually make the lesions go away. There have been better results in reducing itching and lesion prominence with intralesional steroid injections, topical calcipotriol, or calcineurin inhibitors.1 The inflammation usually spontaneously resolves over 3 to 12 months.

The patient was advised that the condition is benign and would likely resolve on its own over time. She was counseled that since the clobetasol was helping with her itching, she could use it (sparingly) as needed. She was cautioned that prolonged usage could lead to skin atrophy.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Al-Balbeesi A. Adult blaschkitis with lichenoid features and blood eosinophilia. Cureus. 2021;13:e16846. doi: 10.7759/cureus.16846

References

1. Al-Balbeesi A. Adult blaschkitis with lichenoid features and blood eosinophilia. Cureus. 2021;13:e16846. doi: 10.7759/cureus.16846

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Cultural humility required to optimize treatment of eczema patients with skin of color

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– Treating atopic dermatitis (AD) in children and adolescents with skin of color requires an acumen that extends well beyond the skin, said Candrice R. Heath, MD, at the annual meeting of the Society for Pediatric Dermatology.

This involves the practice of cultural humility, which Dr. Heath defined as a commitment to learn about all aspects of patients to truly understand them, including their race, access to health care, and socioeconomic status.

“We can continue to prioritize learning about all different types of skin tones and hair types, but we really have to commit to advocating for what our patients deserve in every way,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said during her presentation at the meeting.

“That means advocating for kids to have access to better housing and for increasing health literacy programs in our hospitals, so that all our patients can understand what’s happening and how to navigate the health system,” she said. “It also means increasing diversity in our clinical trials by taking a few extra moments with the patient and family of color who might be eligible to participate in a clinical trial. We have work to do.”

To illustrate her points, she discussed the case of a 6-year-old Black patient, whose parents bring him into the clinic complaining about dark marks on the skin. The areas are itchy and the doctor figures, “this is a slam dunk; this is AD,” Dr. Heath said. “You talk about the diagnosis, and you give your treatment plan.

“But the issue is, in the parking lot when the patient’s family leaves, they feel like you didn’t help them at all,” she continued. “You didn’t understand what they came in for. They didn’t receive a treatment for what they came in for, because the initial complaint was dark marks on the skin, which is postinflammatory hyperpigmentation. We know that patients are distressed by this.”

As evidence, she cited a cross-sectional study that assessed the impact of hyperpigmentation and hyperchromia on quality of life in adults, published in the Journal of the American Academy of Dermatology. People who reported the highest levels of distress were women, those with postinflammatory hyperpigmentation, those with fewer formal years of education, and those who had higher out-of-pocket spending on skin-enhancing products.

“So, when you see hyperpigmentation in your AD patients of color, acknowledge it; say, ‘I see this pigmentation change,’ ” Dr. Heath advised. “Talk about how controlling the AD with a topical steroid or other treatment option can have a positive impact on that.”

However, she added that sometimes patients have steroid phobia, possibly because they believe the topical steroids are causing the pigmentation changes, “especially in cases of hypopigmentation, so I take the time to reassure patients so that they will not be fearful about using the medication.”



Parents of patients with skin of color who have AD may harbor other “invisible” concerns during office visits, she continued, including prior experiences with dermatologists that may not have been positive, difficulty accessing pediatric dermatologists, or a general mistrust of the health care system.

“All of that is going on in the room with your patients, particularly those with skin of color and those who feel marginalized,” said Dr. Heath, who is also a faculty scholar at Temple University medical school’s office of health equity, diversity and inclusion. “Of course, we can’t fix everything. But we can commit to approaching our visits with cultural humility.”

For patients with skin of color, she pointed out, other upstream effects impact AD care and outcomes, including well-documented socioeconomic factors.

“One of the equalizing factors is that we as pediatric dermatologists can think about increasing our education regarding skin of color,” Dr. Heath said.

For example, an analysis of data from the 2002 to 2012 National Inpatient Sample found that the main risk factors for inpatient hospitalization for AD were being non-White, having lowest-quartile household income, and having Medicaid or no insurance, researchers reported in 2018.

A separate multicenter study of 1,437 mother-child pairs with known AD found that non-Hispanic Black children and Hispanic children had greater odds of persistent AD than non-Hispanic White children, according to a 2019 study. Another large prospective cohort study published in 2019 found that AD prevalence and persistence is highest in U.S. urban children who are female or Black, and urban children with AD are more likely to have poor quality of life and asthma.

A few months after that study was published, researchers reported results from an analysis of data from the 2007-2008 National Survey of Children’s Health, which found that children who perceive the neighborhood they lived in as unsafe, unsupportive, or underdeveloped had a higher prevalence of AD and a higher severity of AD. The same year, a study of the social and economic risk factors for moderate to severe AD found that Black children were more likely to come from homes with a lower household income, lower parental education attainment, lack of home ownership, and live between two residences, and have exposure to smoke.

“Disease recognition is one thing, but we also want everyone to be aware of these other factors,” she said, “because some patients do need a little bit more care and help to be able to access the medications that they need and gain access to us.”

 

 

 

Follicular, nummular eczema

In her clinical experience, the most common clinical variants of AD in patients with skin of color is follicular eczema. “Examine the patient, apply your hand to the affected area, and you can feel the papules beneath your fingertips,” she advised.

“That’s what I teach my residents and medical students,” she said. “If you are looking for erythema to seal your diagnosis of AD, it may not happen. You may see more of a violaceous hue and sometimes you may not find it at all, depending on the patient’s skin tone. If I find an area of normal appearing skin and then look back at the area of active skin disease, I go back and forth until I’m able to train my eye to be able to see those violaceous and erythematous hues more easily.”

Nummular eczema can also be a challenge in AD patients with skin of color.

“I like to listen to buzz words,” Dr. Heath said. “If a parent says, ‘my child has been diagnosed with ringworm multiple times,’ I zoom in on that. We know that kids can get tinea corporis, but usually not multiple times. I ask about all the things that can be associated with AD, and often we do see these nummular plaques on the skin and do some education about that. I also talk to their pediatrician or send information to that person so that they can be aware that nummular eczema is a form of AD.”

She noted that AD of the scalp may be confused with tinea capitis, especially in young Black children with moderate to severe AD. In her experience, triamcinolone 0.1% ointment works well for AD of the scalp.

She concluded her presentation by noting that there is no easy solution to treating AD in young patients with skin of color. “It’s way more than just eczema. We can help people see AD in a different way. My goal is to see the value in challenging ourselves to understand the impact of what happens outside of the exam room on these patients.”

Dr. Heath disclosed that she has served as a consultant for several pharmaceutical companies, including Regeneron, Janssen, Arcutis, Johnson and Johnson, Cassiopea, and Lilly.

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– Treating atopic dermatitis (AD) in children and adolescents with skin of color requires an acumen that extends well beyond the skin, said Candrice R. Heath, MD, at the annual meeting of the Society for Pediatric Dermatology.

This involves the practice of cultural humility, which Dr. Heath defined as a commitment to learn about all aspects of patients to truly understand them, including their race, access to health care, and socioeconomic status.

“We can continue to prioritize learning about all different types of skin tones and hair types, but we really have to commit to advocating for what our patients deserve in every way,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said during her presentation at the meeting.

“That means advocating for kids to have access to better housing and for increasing health literacy programs in our hospitals, so that all our patients can understand what’s happening and how to navigate the health system,” she said. “It also means increasing diversity in our clinical trials by taking a few extra moments with the patient and family of color who might be eligible to participate in a clinical trial. We have work to do.”

To illustrate her points, she discussed the case of a 6-year-old Black patient, whose parents bring him into the clinic complaining about dark marks on the skin. The areas are itchy and the doctor figures, “this is a slam dunk; this is AD,” Dr. Heath said. “You talk about the diagnosis, and you give your treatment plan.

“But the issue is, in the parking lot when the patient’s family leaves, they feel like you didn’t help them at all,” she continued. “You didn’t understand what they came in for. They didn’t receive a treatment for what they came in for, because the initial complaint was dark marks on the skin, which is postinflammatory hyperpigmentation. We know that patients are distressed by this.”

As evidence, she cited a cross-sectional study that assessed the impact of hyperpigmentation and hyperchromia on quality of life in adults, published in the Journal of the American Academy of Dermatology. People who reported the highest levels of distress were women, those with postinflammatory hyperpigmentation, those with fewer formal years of education, and those who had higher out-of-pocket spending on skin-enhancing products.

“So, when you see hyperpigmentation in your AD patients of color, acknowledge it; say, ‘I see this pigmentation change,’ ” Dr. Heath advised. “Talk about how controlling the AD with a topical steroid or other treatment option can have a positive impact on that.”

However, she added that sometimes patients have steroid phobia, possibly because they believe the topical steroids are causing the pigmentation changes, “especially in cases of hypopigmentation, so I take the time to reassure patients so that they will not be fearful about using the medication.”



Parents of patients with skin of color who have AD may harbor other “invisible” concerns during office visits, she continued, including prior experiences with dermatologists that may not have been positive, difficulty accessing pediatric dermatologists, or a general mistrust of the health care system.

“All of that is going on in the room with your patients, particularly those with skin of color and those who feel marginalized,” said Dr. Heath, who is also a faculty scholar at Temple University medical school’s office of health equity, diversity and inclusion. “Of course, we can’t fix everything. But we can commit to approaching our visits with cultural humility.”

For patients with skin of color, she pointed out, other upstream effects impact AD care and outcomes, including well-documented socioeconomic factors.

“One of the equalizing factors is that we as pediatric dermatologists can think about increasing our education regarding skin of color,” Dr. Heath said.

For example, an analysis of data from the 2002 to 2012 National Inpatient Sample found that the main risk factors for inpatient hospitalization for AD were being non-White, having lowest-quartile household income, and having Medicaid or no insurance, researchers reported in 2018.

A separate multicenter study of 1,437 mother-child pairs with known AD found that non-Hispanic Black children and Hispanic children had greater odds of persistent AD than non-Hispanic White children, according to a 2019 study. Another large prospective cohort study published in 2019 found that AD prevalence and persistence is highest in U.S. urban children who are female or Black, and urban children with AD are more likely to have poor quality of life and asthma.

A few months after that study was published, researchers reported results from an analysis of data from the 2007-2008 National Survey of Children’s Health, which found that children who perceive the neighborhood they lived in as unsafe, unsupportive, or underdeveloped had a higher prevalence of AD and a higher severity of AD. The same year, a study of the social and economic risk factors for moderate to severe AD found that Black children were more likely to come from homes with a lower household income, lower parental education attainment, lack of home ownership, and live between two residences, and have exposure to smoke.

“Disease recognition is one thing, but we also want everyone to be aware of these other factors,” she said, “because some patients do need a little bit more care and help to be able to access the medications that they need and gain access to us.”

 

 

 

Follicular, nummular eczema

In her clinical experience, the most common clinical variants of AD in patients with skin of color is follicular eczema. “Examine the patient, apply your hand to the affected area, and you can feel the papules beneath your fingertips,” she advised.

“That’s what I teach my residents and medical students,” she said. “If you are looking for erythema to seal your diagnosis of AD, it may not happen. You may see more of a violaceous hue and sometimes you may not find it at all, depending on the patient’s skin tone. If I find an area of normal appearing skin and then look back at the area of active skin disease, I go back and forth until I’m able to train my eye to be able to see those violaceous and erythematous hues more easily.”

Nummular eczema can also be a challenge in AD patients with skin of color.

“I like to listen to buzz words,” Dr. Heath said. “If a parent says, ‘my child has been diagnosed with ringworm multiple times,’ I zoom in on that. We know that kids can get tinea corporis, but usually not multiple times. I ask about all the things that can be associated with AD, and often we do see these nummular plaques on the skin and do some education about that. I also talk to their pediatrician or send information to that person so that they can be aware that nummular eczema is a form of AD.”

She noted that AD of the scalp may be confused with tinea capitis, especially in young Black children with moderate to severe AD. In her experience, triamcinolone 0.1% ointment works well for AD of the scalp.

She concluded her presentation by noting that there is no easy solution to treating AD in young patients with skin of color. “It’s way more than just eczema. We can help people see AD in a different way. My goal is to see the value in challenging ourselves to understand the impact of what happens outside of the exam room on these patients.”

Dr. Heath disclosed that she has served as a consultant for several pharmaceutical companies, including Regeneron, Janssen, Arcutis, Johnson and Johnson, Cassiopea, and Lilly.

– Treating atopic dermatitis (AD) in children and adolescents with skin of color requires an acumen that extends well beyond the skin, said Candrice R. Heath, MD, at the annual meeting of the Society for Pediatric Dermatology.

This involves the practice of cultural humility, which Dr. Heath defined as a commitment to learn about all aspects of patients to truly understand them, including their race, access to health care, and socioeconomic status.

“We can continue to prioritize learning about all different types of skin tones and hair types, but we really have to commit to advocating for what our patients deserve in every way,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said during her presentation at the meeting.

“That means advocating for kids to have access to better housing and for increasing health literacy programs in our hospitals, so that all our patients can understand what’s happening and how to navigate the health system,” she said. “It also means increasing diversity in our clinical trials by taking a few extra moments with the patient and family of color who might be eligible to participate in a clinical trial. We have work to do.”

To illustrate her points, she discussed the case of a 6-year-old Black patient, whose parents bring him into the clinic complaining about dark marks on the skin. The areas are itchy and the doctor figures, “this is a slam dunk; this is AD,” Dr. Heath said. “You talk about the diagnosis, and you give your treatment plan.

“But the issue is, in the parking lot when the patient’s family leaves, they feel like you didn’t help them at all,” she continued. “You didn’t understand what they came in for. They didn’t receive a treatment for what they came in for, because the initial complaint was dark marks on the skin, which is postinflammatory hyperpigmentation. We know that patients are distressed by this.”

As evidence, she cited a cross-sectional study that assessed the impact of hyperpigmentation and hyperchromia on quality of life in adults, published in the Journal of the American Academy of Dermatology. People who reported the highest levels of distress were women, those with postinflammatory hyperpigmentation, those with fewer formal years of education, and those who had higher out-of-pocket spending on skin-enhancing products.

“So, when you see hyperpigmentation in your AD patients of color, acknowledge it; say, ‘I see this pigmentation change,’ ” Dr. Heath advised. “Talk about how controlling the AD with a topical steroid or other treatment option can have a positive impact on that.”

However, she added that sometimes patients have steroid phobia, possibly because they believe the topical steroids are causing the pigmentation changes, “especially in cases of hypopigmentation, so I take the time to reassure patients so that they will not be fearful about using the medication.”



Parents of patients with skin of color who have AD may harbor other “invisible” concerns during office visits, she continued, including prior experiences with dermatologists that may not have been positive, difficulty accessing pediatric dermatologists, or a general mistrust of the health care system.

“All of that is going on in the room with your patients, particularly those with skin of color and those who feel marginalized,” said Dr. Heath, who is also a faculty scholar at Temple University medical school’s office of health equity, diversity and inclusion. “Of course, we can’t fix everything. But we can commit to approaching our visits with cultural humility.”

For patients with skin of color, she pointed out, other upstream effects impact AD care and outcomes, including well-documented socioeconomic factors.

“One of the equalizing factors is that we as pediatric dermatologists can think about increasing our education regarding skin of color,” Dr. Heath said.

For example, an analysis of data from the 2002 to 2012 National Inpatient Sample found that the main risk factors for inpatient hospitalization for AD were being non-White, having lowest-quartile household income, and having Medicaid or no insurance, researchers reported in 2018.

A separate multicenter study of 1,437 mother-child pairs with known AD found that non-Hispanic Black children and Hispanic children had greater odds of persistent AD than non-Hispanic White children, according to a 2019 study. Another large prospective cohort study published in 2019 found that AD prevalence and persistence is highest in U.S. urban children who are female or Black, and urban children with AD are more likely to have poor quality of life and asthma.

A few months after that study was published, researchers reported results from an analysis of data from the 2007-2008 National Survey of Children’s Health, which found that children who perceive the neighborhood they lived in as unsafe, unsupportive, or underdeveloped had a higher prevalence of AD and a higher severity of AD. The same year, a study of the social and economic risk factors for moderate to severe AD found that Black children were more likely to come from homes with a lower household income, lower parental education attainment, lack of home ownership, and live between two residences, and have exposure to smoke.

“Disease recognition is one thing, but we also want everyone to be aware of these other factors,” she said, “because some patients do need a little bit more care and help to be able to access the medications that they need and gain access to us.”

 

 

 

Follicular, nummular eczema

In her clinical experience, the most common clinical variants of AD in patients with skin of color is follicular eczema. “Examine the patient, apply your hand to the affected area, and you can feel the papules beneath your fingertips,” she advised.

“That’s what I teach my residents and medical students,” she said. “If you are looking for erythema to seal your diagnosis of AD, it may not happen. You may see more of a violaceous hue and sometimes you may not find it at all, depending on the patient’s skin tone. If I find an area of normal appearing skin and then look back at the area of active skin disease, I go back and forth until I’m able to train my eye to be able to see those violaceous and erythematous hues more easily.”

Nummular eczema can also be a challenge in AD patients with skin of color.

“I like to listen to buzz words,” Dr. Heath said. “If a parent says, ‘my child has been diagnosed with ringworm multiple times,’ I zoom in on that. We know that kids can get tinea corporis, but usually not multiple times. I ask about all the things that can be associated with AD, and often we do see these nummular plaques on the skin and do some education about that. I also talk to their pediatrician or send information to that person so that they can be aware that nummular eczema is a form of AD.”

She noted that AD of the scalp may be confused with tinea capitis, especially in young Black children with moderate to severe AD. In her experience, triamcinolone 0.1% ointment works well for AD of the scalp.

She concluded her presentation by noting that there is no easy solution to treating AD in young patients with skin of color. “It’s way more than just eczema. We can help people see AD in a different way. My goal is to see the value in challenging ourselves to understand the impact of what happens outside of the exam room on these patients.”

Dr. Heath disclosed that she has served as a consultant for several pharmaceutical companies, including Regeneron, Janssen, Arcutis, Johnson and Johnson, Cassiopea, and Lilly.

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