Flesh-Colored Pinpoint Papules With Fine White Spicules on the Upper Body

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Flesh-Colored Pinpoint Papules With Fine White Spicules on the Upper Body

The Diagnosis: Trichodysplasia Spinulosa

A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.

Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.

Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.

The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8

Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11

Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.

Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16

References
  1. Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
  2. Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
  3. Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
  4. Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
  5. Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
  6. Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
  7. Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
  8. Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
  9. Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
  10. Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
  11. Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
  12. Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
  13. Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
  14. Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
  15. Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
  16. Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
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From The Ohio State University, Columbus. Dr. Hobayan is from the College of Medicine, Dr. Korman is from the Department of Dermatology, and Dr. Lin is from the Department of Internal Medicine, Division of Rheumatology and Immunology.

The authors report no conflict of interest.

Correspondence: Catherine Grace Plan Hobayan, MD, The Ohio State University College of Medicine, 370 W 9th Ave, Columbus, OH 43210 ([email protected]).

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From The Ohio State University, Columbus. Dr. Hobayan is from the College of Medicine, Dr. Korman is from the Department of Dermatology, and Dr. Lin is from the Department of Internal Medicine, Division of Rheumatology and Immunology.

The authors report no conflict of interest.

Correspondence: Catherine Grace Plan Hobayan, MD, The Ohio State University College of Medicine, 370 W 9th Ave, Columbus, OH 43210 ([email protected]).

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From The Ohio State University, Columbus. Dr. Hobayan is from the College of Medicine, Dr. Korman is from the Department of Dermatology, and Dr. Lin is from the Department of Internal Medicine, Division of Rheumatology and Immunology.

The authors report no conflict of interest.

Correspondence: Catherine Grace Plan Hobayan, MD, The Ohio State University College of Medicine, 370 W 9th Ave, Columbus, OH 43210 ([email protected]).

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The Diagnosis: Trichodysplasia Spinulosa

A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.

Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.

Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.

The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8

Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11

Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.

Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16

The Diagnosis: Trichodysplasia Spinulosa

A diagnosis of trichodysplasia spinulosa (TS) was rendered based on the clinical presentation— diffuse folliculocentric keratotic papules with spicules and leonine facies—coinciding with cyclosporine initiation. Biopsy was deferred given the classic presentation. The patient applied cidofovir cream 1% daily to lesions on the face. She was prescribed leflunomide 10 mg daily, which was later increased to 20 mg daily, for polyarthritis associated with systemic lupus erythematosus (SLE). Her transplant physician increased her cyclosporine dosage from 50 mg twice daily to 75 mg each morning and 50 mg each evening due to rising creatinine and donor-specific antibodies from the renal transplant. The patient’s TS eruption mildly improved 3 months after the cyclosporine dose was increased. To treat persistent lesions, oral valganciclovir was started at 450 mg once daily and later reduced to every other day due to leukopenia. After 3 months of taking valganciclovir 450 mg every other day, the patient’s TS rash resolved.

Trichodysplasia spinulosa is a rare condition caused by TS-associated polyomavirus1 that may arise in immunosuppressed patients, especially in solid organ transplant recipients.2 It is characterized by spiculated and folliculocentric papules, mainly on the face,1 and often is diagnosed clinically, but if the presentation is not classic, a skin biopsy can help to confirm the diagnosis. Because of its rarity, treatment options do not have well-established efficacy1 but include reducing immunosuppression and using the antivirals cidofovir1 or valganciclovir3 to treat the polyomavirus. Topical retinoids,3 photodynamic therapy, 4 and leflunomide5 also may be effective.

Although the typical approach to treating TS is to reduce immunosuppression, this was not an option for our patient, as she required increased immunosuppression for the treatment of active SLE. Leflunomide can be used for SLE, and in some reports it can be effective for BK viremia in kidney transplant recipients5 as well as for TS in solid organ transplant recipients.6 Our patient showed improvement of the TS, BK viremia, renal function, and SLE while taking leflunomide and valganciclovir.

The differential diagnosis includes keratosis pilaris, lichen nitidus, scleromyxedema, and trichostasis spinulosa. Keratosis pilaris is a benign skin disorder consisting of patches of keratotic papules with varying degrees of erythema and inflammation that are formed by dead keratinocytes plugging the hair follicles and often are seen on the extremities, face, and trunk.7 Our patient’s papules were flesh colored with no notable background erythema. Additionally, the presence of leonine facies was atypical for keratosis pilaris. Acids, steroids, and kinase inhibitors are the most frequently used treatments for keratosis pilaris.8

Lichen nitidus is a skin condition characterized by multiple shiny, dome-shaped, flesh-colored papules usually found on the flexor surfaces of the arms, anterior trunk, and genitalia. It is mostly asymptomatic, but patients may experience pruritus. Most cases occur in children and young adults, with no obvious racial or gender predilection. The diagnosis often is clinical, but biopsy shows downward enlargement of the epidermal rete ridges surrounding a focal inflammatory infiltrate, known as a ball-in-claw configuration.9-11 Lichen nitidus spontaneously resolves within a few years without treatment. Our patient did have flesh-colored papules on the arms and chest; however, major involvement of the face is not typical in lichen nitidus. Additionally, fine white spicules would not be seen in lichen nitidus. For severe generalized lichen nitidus, treatment options include topical corticosteroids, topical calcineurin inhibitors, oral antihistamines, or UV light to decrease inflammation.9-11

Scleromyxedema is a rare condition involving the deposition of mucinous material in the papillary dermis to cause the formation of infiltrative skin lesions.12 It is thought that immunoglobulins and cytokines secreted by inflammatory cells lead to the synthesis of glycosaminoglycans, which then causes deposition of mucin in the dermis.13 The classic cutaneous features of scleromyxedema include waxy indurated papules and plaques with skin thickening throughout the entire body.12 Our patient’s papules were not notably indurated and involved less than 50% of the total body surface area. An important diagnostic feature of scleromyxedema is monoclonal gammopathy, which our patient did not have. Intravenous immunoglobulin is the first-line treatment of scleromyxedema, and second-line treatments include systemic corticosteroids and thalidomide.14 Our patient also did not require treatment with intravenous immunoglobulin, as her rash improved with antiviral medication, which would not address the underlying inflammatory processes associated with scleromyxedema.

Trichostasis spinulosa is a rare hair follicle disorder consisting of dark, spiny, hyperkeratotic follicular papules that can be found on the extremities and face, especially the nose. The etiology is unknown, but risk factors include congenital dysplasia of hair follicles; exposure to UV light, dust, oil, or heat; chronic renal failure; Malassezia yeast; and Propionibacterium acnes. Adult women with darker skin types are most commonly affected by trichostasis spinulosa.15,16 Our patient fit the epidemiologic demographic of trichostasis spinulosa, including a history of chronic renal failure. Her rash covered the face, nose, and arms; however, the papules were flesh colored, whereas trichostasis spinulosa would appear as black papules. Furthermore, yeast and bacterial infections have been identified as potential agents associated with trichostasis spinulosa; therefore, antiviral agents would be ineffective. Viable treatments for trichostasis spinulosa include emollients, topical keratolytic agents, retinoic acids, and lasers to remove abnormal hair follicles.15,16

References
  1. Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
  2. Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
  3. Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
  4. Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
  5. Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
  6. Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
  7. Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
  8. Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
  9. Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
  10. Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
  11. Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
  12. Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
  13. Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
  14. Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
  15. Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
  16. Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
References
  1. Curman P, Näsman A, Brauner H. Trichodysplasia spinulosa: a comprehensive disease and its treatment. J Eur Acad Dermatol Venereol. 2021;35:1067-1076.
  2. Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol. 2021;148:726-733.
  3. Shah PR, Esaa FS, Gupta P, et al. Trichodysplasia spinulosa successfully treated with adapalene 0.1% gel and oral valganciclovir in a renal transplant recipient. JAAD Case Rep. 2020;6:23-25.
  4. Liew YCC, Kee TYS, Kwek JL, et al. Photodynamic therapy for the treatment of trichodysplasia spinulosa in an Asian renal transplant recipient: a case report and review of the literature. JAAD Case Rep. 2021;7:74-83.
  5. Pierrotti LC, Urbano PRP, da Silva Nali LH, et al. Viremia and viuria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient. Transpl Infect Dis. 2019;21:E13133.
  6. Kassar R, Chang J, Chan AW, et al. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transpl Infect Dis. 2017;19:E12702.
  7. Eckburg A, Kazemi T, Maguiness S. Keratosis pilaris rubra successfully treated with topical sirolimus: report of a case and review of the literature. Pediatr Dermatol. 2022;39:429-431.
  8. Reddy S, Brahmbhatt H. A narrative review on the role of acids, steroids, and kinase inhibitors in the treatment of keratosis pilaris. Cureus. 2021;13:E18917.
  9. Jordan AS, Green MC, Sulit DJ. Lichen nitidus. J Am Osteopath Assoc. 2019;119:704.
  10. Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin Exp Dermatol. 2002;27:115-117.
  11. Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186:E688.
  12. Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.
  13. Christman MP, Sukhdeo K, Kim RH, et al. Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular type). Dermatol Online J. 2017;23:8.
  14. Hoffman JHO, Enk AH. Scleromyxedema. J Dtsch Dermatol Ges. 2020;18:1449-1467.
  15. Kositkuljorn C, Suchonwanit P. Trichostasis spinulosa: a case report with an unusual presentation. Case Rep Dermatol. 2020;12:178-185.
  16. Ramteke MN, Bhide AA. Trichostasis spinulosa at an unusual site. Int J Trichology. 2016;8:78-80.
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A 54-year-old Black woman presented with a rash that developed 6 months after a renal transplant due to a history of systemic lupus erythematosus with lupus nephritis. She was started on mycophenolate mofetil and tacrolimus after the transplant but was switched to cyclosporine because of BK viremia. The rash developed 1 week after cyclosporine was initiated and consisted of pruritic papules that started on the face and spread to the trunk and arms. Physical examination revealed innumerable follicular-based, keratotic, flesh-colored, pinpoint papules with fine white spicules on the face (top), neck, chest, arms, and back. Leonine facies was seen along the glabella with madarosis of the lateral eyebrows (top) and ears (bottom).

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Is Location a Risk Factor for Early-Onset Cancer?

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Early-onset cancer—diagnosed in adults aged ≤ 50 years—is on the rise. Researchers have studied a variety of factors driving the trend, such as type of cancer. However, geographic locality might have as much, if not more, to do with it, according to a study by researchers at Fox Chase Cancer Center, a National Cancer Institute-designated Comprehensive Cancer Center research facility.

Using the US Cancer Statistics Public Use Research Database, the researchers collected data from adults aged 20 to 49 years with invasive cancer (excluding in situ cases) diagnosed from 2015 through 2020. They calculated the incidence for each state using the national rate as the reference. Then, they calculated a second set of rates, comparing each state to the US in terms of overall incidence and advanced-stage incidence for all early-onset cancers.

The resulting maps indicated that early-onset cancer cases are not evenly distributed. States with worse-than-national rates are frequently near each other geographically. For instance, the rate of early-onset female breast cancer was worse than the national rate in 17 states, 16 of which were located in the eastern half of the US (Hawaii was the 17th state). Similarly, most states with worse-than-national rates of digestive cancers were located in the eastern half of the US, with a concentration in the South. Rates of male genital cancers were worse than national rates in 18 states, primarily in the eastern half of the country (plus Montana, Nebraska, and Puerto Rico).

Three states in the Southeast, 7 in the Northeast, and Puerto Rico had the highest incidence of lymphohematopoietic cancers. Incidence rates of endocrine cancers were worse than national rates in 25 states, which the researchers found formed “a horizontal core of the country running from east to west,” plus Puerto Rico. Rates of urinary system cancers were worse than national rates in 17 contiguous states, from New Mexico to Pennsylvania.

Rates of female genital cancers were worse than national rates in 16 states, largely in the Midwest and South, plus California and Puerto Rico. Skin cancer, on the other hand, was a great leveler, with worse-than-national rates in 32 states, mostly in the northern portion of the country.

Kentucky and West Virginia had the highest overall and advanced-stage incidence rates of early-onset cancer for all cancer sites combined. They were followed by Arkansas, Connecticut, Florida, Georgia, Iowa, Louisiana, Maine, Missouri, New Jersey, New York, North Carolina, Ohio, and Pennsylvania.

According to the researchers, this study provides the first analysis of age-adjusted rates of early-onset cancer based on state-level population and case numbers. Geographic patterns in early-onset cancer, they suggest, indicate possible similarities that could relate to demographic, socioeconomic, behavioral, or environmental risks. “Focusing prevention efforts on the highest-incidence states for the most prevalent sites may reduce the rate of early-onset cancer nationally.”

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Early-onset cancer—diagnosed in adults aged ≤ 50 years—is on the rise. Researchers have studied a variety of factors driving the trend, such as type of cancer. However, geographic locality might have as much, if not more, to do with it, according to a study by researchers at Fox Chase Cancer Center, a National Cancer Institute-designated Comprehensive Cancer Center research facility.

Using the US Cancer Statistics Public Use Research Database, the researchers collected data from adults aged 20 to 49 years with invasive cancer (excluding in situ cases) diagnosed from 2015 through 2020. They calculated the incidence for each state using the national rate as the reference. Then, they calculated a second set of rates, comparing each state to the US in terms of overall incidence and advanced-stage incidence for all early-onset cancers.

The resulting maps indicated that early-onset cancer cases are not evenly distributed. States with worse-than-national rates are frequently near each other geographically. For instance, the rate of early-onset female breast cancer was worse than the national rate in 17 states, 16 of which were located in the eastern half of the US (Hawaii was the 17th state). Similarly, most states with worse-than-national rates of digestive cancers were located in the eastern half of the US, with a concentration in the South. Rates of male genital cancers were worse than national rates in 18 states, primarily in the eastern half of the country (plus Montana, Nebraska, and Puerto Rico).

Three states in the Southeast, 7 in the Northeast, and Puerto Rico had the highest incidence of lymphohematopoietic cancers. Incidence rates of endocrine cancers were worse than national rates in 25 states, which the researchers found formed “a horizontal core of the country running from east to west,” plus Puerto Rico. Rates of urinary system cancers were worse than national rates in 17 contiguous states, from New Mexico to Pennsylvania.

Rates of female genital cancers were worse than national rates in 16 states, largely in the Midwest and South, plus California and Puerto Rico. Skin cancer, on the other hand, was a great leveler, with worse-than-national rates in 32 states, mostly in the northern portion of the country.

Kentucky and West Virginia had the highest overall and advanced-stage incidence rates of early-onset cancer for all cancer sites combined. They were followed by Arkansas, Connecticut, Florida, Georgia, Iowa, Louisiana, Maine, Missouri, New Jersey, New York, North Carolina, Ohio, and Pennsylvania.

According to the researchers, this study provides the first analysis of age-adjusted rates of early-onset cancer based on state-level population and case numbers. Geographic patterns in early-onset cancer, they suggest, indicate possible similarities that could relate to demographic, socioeconomic, behavioral, or environmental risks. “Focusing prevention efforts on the highest-incidence states for the most prevalent sites may reduce the rate of early-onset cancer nationally.”

Early-onset cancer—diagnosed in adults aged ≤ 50 years—is on the rise. Researchers have studied a variety of factors driving the trend, such as type of cancer. However, geographic locality might have as much, if not more, to do with it, according to a study by researchers at Fox Chase Cancer Center, a National Cancer Institute-designated Comprehensive Cancer Center research facility.

Using the US Cancer Statistics Public Use Research Database, the researchers collected data from adults aged 20 to 49 years with invasive cancer (excluding in situ cases) diagnosed from 2015 through 2020. They calculated the incidence for each state using the national rate as the reference. Then, they calculated a second set of rates, comparing each state to the US in terms of overall incidence and advanced-stage incidence for all early-onset cancers.

The resulting maps indicated that early-onset cancer cases are not evenly distributed. States with worse-than-national rates are frequently near each other geographically. For instance, the rate of early-onset female breast cancer was worse than the national rate in 17 states, 16 of which were located in the eastern half of the US (Hawaii was the 17th state). Similarly, most states with worse-than-national rates of digestive cancers were located in the eastern half of the US, with a concentration in the South. Rates of male genital cancers were worse than national rates in 18 states, primarily in the eastern half of the country (plus Montana, Nebraska, and Puerto Rico).

Three states in the Southeast, 7 in the Northeast, and Puerto Rico had the highest incidence of lymphohematopoietic cancers. Incidence rates of endocrine cancers were worse than national rates in 25 states, which the researchers found formed “a horizontal core of the country running from east to west,” plus Puerto Rico. Rates of urinary system cancers were worse than national rates in 17 contiguous states, from New Mexico to Pennsylvania.

Rates of female genital cancers were worse than national rates in 16 states, largely in the Midwest and South, plus California and Puerto Rico. Skin cancer, on the other hand, was a great leveler, with worse-than-national rates in 32 states, mostly in the northern portion of the country.

Kentucky and West Virginia had the highest overall and advanced-stage incidence rates of early-onset cancer for all cancer sites combined. They were followed by Arkansas, Connecticut, Florida, Georgia, Iowa, Louisiana, Maine, Missouri, New Jersey, New York, North Carolina, Ohio, and Pennsylvania.

According to the researchers, this study provides the first analysis of age-adjusted rates of early-onset cancer based on state-level population and case numbers. Geographic patterns in early-onset cancer, they suggest, indicate possible similarities that could relate to demographic, socioeconomic, behavioral, or environmental risks. “Focusing prevention efforts on the highest-incidence states for the most prevalent sites may reduce the rate of early-onset cancer nationally.”

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Inpatient Management of Hidradenitis Suppurativa: A Delphi Consensus Study

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Inpatient Management of Hidradenitis Suppurativa: A Delphi Consensus Study

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects approximately 0.1% of the US population.1,2 Severe disease or HS flares can lead patients to seek care through the emergency department (ED), with some requiring inpatient admission. 3 Inpatient hospitalization of patients with HS has increased over the last 2 decades, and patients with HS utilize emergency and inpatient care more frequently than those with other dermatologic conditions.4,5 Minority patients and those of lower socioeconomic status are more likely to present to the ED for HS management due to limited access to care and other existing comorbid conditions. 4 In a 2022 study of the Nationwide Readmissions Database, the authors looked at hospital readmission rates of patients with HS compared with those with heart failure—both patient populations with chronic debilitating conditions. Results indicated that the hospital readmission rates for patients with HS surpassed those of patients with heart failure for that year, highlighting the need for improved inpatient management of HS.6

Patients with HS present to the ED with severe pain, fever, wound care, or the need for surgical intervention. The ED and inpatient hospital setting are locations in which physicians may not be as familiar with the diagnosis or treatment of HS, specifically flares or severe disease. 7 The inpatient care setting provides access to certain resources that can be challenging to obtain in the outpatient clinical setting, such as social workers and pain specialists, but also can prove challenging in obtaining other resources for HS management, such as advanced medical therapies. Given the increase in hospital- based care for HS and lack of widespread inpatient access to dermatology and HS experts, consensus recommendations for management of HS in the acute hospital setting would be beneficial. In our study, we sought to generate a collection of expert consensus statements providers can refer to when managing patients with HS in the inpatient setting.

Methods

The study team at the Wake Forest University School of Medicine (Winston-Salem, North Carolina)(M.N., R.P., L.C.S.) developed an initial set of consensus statements based on current published HS treatment guidelines,8,9 publications on management of inpatient HS,3 published supportive care guidelines for Stevens-Johnson syndrome, 10 and personal clinical experience in managing inpatient HS, which resulted in 50 statements organized into the following categories: overall care, wound care, genital care, pain management, infection control, medical management, surgical management, nutrition, and transitional care guidelines. This study was approved by the Wake Forest University institutional review board (IRB00084257).

Participant Recruitment—Dermatologists were identified for participation in the study based on membership in the Society of Dermatology Hospitalists and the Hidradenitis Suppurativa Foundation or authorship of publications relevant to HS or inpatient dermatology. Dermatologists from larger academic institutions with HS specialty clinics and inpatient dermatology services also were identified. Participants were invited via email and could suggest other experts for inclusion. A total of 31 dermatologists were invited to participate in the study, with 26 agreeing to participate. All participating dermatologists were practicing in the United States.

Delphi Study—In the first round of the Delphi study, the participants were sent an online survey via REDCap in which they were asked to rank the appropriateness of each of the proposed 50 guideline statements on a scale of 1 (very inappropriate) to 9 (very appropriate). Participants also were able to provide commentary and feedback on each of the statements. Survey results were analyzed using the RAND/ UCLA Appropriateness Method.11 For each statement, the median rating for appropriateness, interpercentile range (IPR), IPR adjusted for symmetry, and disagreement index (DI) were calculated (DI=IPR/IPR adjusted for symmetry). The 30th and 70th percentiles were used in the DI calculation as the upper and lower limits, respectively. A median rating for appropriateness of 1.0 to 3.9 was considered “inappropriate,” 4.0 to 6.9 was considered “uncertain appropriateness,” and 7.0 to 9.0 was “appropriate.” A DI value greater than or equal to 1 indicated a lack of consensus regarding the appropriateness of the statement. Following each round, participants received a copy of their responses along with the group median rank of each statement. Statements that did not reach consensus in the first Delphi round were revised based on feedback received by the participants, and a second survey with 14 statements was sent via REDCap 2 weeks later. The RAND/UCLA Appropriateness Method also was applied to this second Delphi round. After the second survey, participants received a copy of anonymized comments regarding the consensus statements and were allowed to provide additional final commentary to be included in the discussion of these recommendations.

Results

Twenty-six dermatologists completed the first-round survey, and 24 participants completed the second-round survey. All participants self-identified as having expertise in either HS (n=22 [85%]) or inpatient dermatology (n=17 [65%]), and 13 (50%) participants self-identified as experts in both HS and inpatient dermatology. All participants, except 1, were affiliated with an academic health system with inpatient dermatology services. The average length of time in practice as a dermatologist was 10 years (median, 9 years [range, 3–27 years]).

Of the 50 initial proposed consensus statements, 26 (52%) achieved consensus after the first round; 21 statements revealed DI calculations that did not achieve consensus. Two statements achieved consensus but received median ratings for appropriateness, indicating uncertain appropriateness; because of this, 1 statement was removed and 1 was revised based on participant feedback, resulting in 13 revised statements (eTable 1). Controversial topics in the consensus process included obtaining wound cultures and meaningful culture data interpretation, use of specific biologic medications in the inpatient setting, and use of intravenous ertapenem. Participant responses to these topics are discussed in detail below. Of these secondround statements, all achieved consensus. The final set of consensus statements can be found in eTable 2.

Comment

Our Delphi consensus study combined the expertise of both dermatologists who care for patients with HS and those with inpatient dermatology experience to produce a set of recommendations for the management of HS in the hospital care setting. A strength of this study is inclusion of many national leaders in both HS and inpatient dermatology, with some participants having developed the previously published HS treatment guidelines and others having participated in inpatient dermatology Delphi studies.8-10 The expertise is further strengthened by the geographically diverse institutional representation within the United States.

The final consensus recommendations included 40 statements covering a range of patient care issues, including use of appropriate inpatient subspecialists (care team), supportive care measures (wound care, pain control, genital care), disease-oriented treatment (medical management, surgical management), inpatient complications (infection control, nutrition), and successful transition back to outpatient management (transitional care). These recommendations are meant to serve as a resource for providers to consider when taking care of inpatient HS flares, recognizing that the complexity and individual circumstances of each patient are unique.

Delphi Consensus Recommendations Compared to Prior Guidelines—Several recommendations in the current study align with the previously published North American clinical management guidelines for HS.8,9 Our recommendations agree with prior guidelines on the importance of disease staging and pain assessment using validated assessment tools as well as screening for HS comorbidities. There also is agreement in the potential benefit of involving pain specialists in the development of a comprehensive pain management plan. The inpatient care setting provides a unique opportunity to engage multiple specialists and collaborate on patient care in a timely manner. Our recommendations regarding surgical care also align with established guidelines in recommending incision and drainage as an acute bedside procedure best utilized for symptom relief in inflamed abscesses and relegating most other surgical management to the outpatient setting. Wound care recommendations also are similar, with our expert participants agreeing on individualizing dressing choices based on wound characteristics. A benefit of inpatient wound care is access to skilled nursing for dressing changes and potentially improved access to more sophisticated dressing materials. Our recommendations differ from the prior guidelines in our focus on severe HS, HS flares, and HS complications, which constitute the majority of inpatient disease management. We provide additional guidance on management of secondary infections, perianal fistulous disease, and importantly transitional care to optimize discharge planning.

Differing Opinions in Our Analysis—Despite the success of our Delphi consensus process, there were some differing opinions regarding certain aspects of inpatient HS management, which is to be expected given the lack of strong evidence-based research to support some of the recommended practices. There were differing opinions on the utility of wound culture data, with some participants feeling culture data could help with antibiotic susceptibility and resistance patterns, while others felt wound cultures represent bacterial colonization or biofilm formation.

Initial consensus statements in the first Delphi round were created for individual biologic medications but did not achieve consensus, and feedback on the use of biologics in the inpatient environment was mixed, largely due to logistic and insurance issues. Many participants felt biologic medication cost, difficulty obtaining inpatient reimbursement, health care resource utilization, and availability of biologics in different hospital systems prevented recommending the use of specific biologics during hospitalization. The one exception was in the case of a hospitalized patient who was already receiving infliximab for HS: there was consensus on ensuring the patient dosing was maximized, if appropriate, to 10 mg/kg.12 Ertapenem use also was controversial, with some participants using it as a bridge therapy to either outpatient biologic use or surgery, while others felt it was onerous and difficult to establish reliable access to secure intravenous administration and regular dosing once the patient left the inpatient setting.13 Others said they have experienced objections from infectious disease colleagues on the use of intravenous antibiotics, citing antibiotic stewardship concerns.

Patient Care in the Inpatient Setting—Prior literature suggests patients admitted as inpatients for HS tend to be of lower socioeconomic status and are admitted to larger urban teaching hospitals.14,15 Patients with lower socioeconomic status have increased difficulty accessing health care resources; therefore, inpatient admission serves as an opportunity to provide a holistic HS assessment and coordinate resources for chronic outpatient management.

Study Limitations—This Delphi consensus study has some limitations. The existing literature on inpatient management of HS is limited, challenging our ability to assess the extent to which these published recommendations are already being implemented. Additionally, the study included HS and inpatient dermatology experts from the United States, which means the recommendations may not be generalizable to other countries. Most participants practiced dermatology at large tertiary care academic medical centers, which may limit the ability to implement recommendations in all US inpatient care settings such as small community-based hospitals; however, many of the supportive care guidelines such as pain control, wound care, nutritional support, and social work should be achievable in most inpatient care settings.

Conclusion

Given the increase in inpatient and ED health care utilization for HS, there is an urgent need for expert consensus recommendations on inpatient management of this unique patient population, which requires complex multidisciplinary care. Our recommendations are a resource for providers to utilize and potentially improve the standard of care we provide these patients.

Acknowledgment—We thank the Wake Forest University Clinical and Translational Science Institute (Winston- Salem, North Carolina) for providing statistical help.

References
  1. Garg A, Kirby JS, Lavian J, et al. Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States. JAMA Dermatol. 2017;153:760-764.
  2. Ingram JR. The epidemiology of hidradenitis suppurativa. Br J Dermatol. 2020;183:990-998. doi:10.1111/bjd.19435
  3. Charrow A, Savage KT, Flood K, et al. Hidradenitis suppurativa for the dermatologic hospitalist. Cutis. 2019;104:276-280.
  4. Anzaldi L, Perkins JA, Byrd AS, et al. Characterizing inpatient hospitalizations for hidradenitis suppurativa in the United States. J Am Acad Dermatol. 2020;82:510-513. doi:10.1016/j.jaad.2019.09.019
  5. Khalsa A, Liu G, Kirby JS. Increased utilization of emergency department and inpatient care by patients with hidradenitis suppurativa. J Am Acad Dermatol. 2015;73:609-614. doi:10.1016/j.jaad.2015.06.053
  6. Edigin E, Kaul S, Eseaton PO, et al. At 180 days hidradenitis suppurativa readmission rate is comparable to heart failure: analysis of the nationwide readmissions database. J Am Acad Dermatol. 2022;87:188-192. doi:10.1016/j.jaad.2021.06.894
  7. Kirby JS, Miller JJ, Adams DR, et al. Health care utilization patterns and costs for patients with hidradenitis suppurativa. JAMA Dermatol. 2014;150:937-944. doi:10.1001/jamadermatol.2014.691
  8. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part I: diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019;81:76-90. doi:10.1016/j .jaad.2019.02.067
  9. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101. doi:10.1016/j.jaad.2019.02.068
  10. Seminario-Vidal L, Kroshinsky D, Malachowski SJ, et al. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020;82:1553-1567. doi:10.1016/j .jaad.2020.02.066
  11. Fitch K, Bernstein SJ, Burnand B, et al. The RAND/UCLA Appropriateness Method: User’s Manual. Rand; 2001.
  12. Oskardmay AN, Miles JA, Sayed CJ. Determining the optimal dose of infliximab for treatment of hidradenitis suppurativa. J Am Acad Dermatol. 2019;81:702-708. doi:10.1016/j.jaad.2019.05.022
  13. Join-Lambert O, Coignard-Biehler H, Jais JP, et al. Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients. J Antimicrob Chemother. 2016;71:513-520. doi:10.1093/jac/dkv361
  14. Khanna R, Whang KA, Huang AH, et al. Inpatient burden of hidradenitis suppurativa in the United States: analysis of the 2016 National Inpatient Sample. J Dermatolog Treat. 2022;33:1150-1152. doi:10.1080/09 546634.2020.1773380
  15. Patel A, Patel A, Solanki D, et al. Hidradenitis suppurativa in the United States: insights from the national inpatient sample (2008-2017) on contemporary trends in demographics, hospitalization rates, chronic comorbid conditions, and mortality. Cureus. 2022;14:E24755. doi:10.7759/cureus.24755
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Author and Disclosure Information

McKenzie Needham and Drs. Pichardo and Strowd are from the Wake Forest University School of Medicine, Winston-Salem, North Carolina. Drs. Pichardo and Strowd also are from the Department of Dermatology, Atrium Health Wake Forest Baptist, Winston-Salem. Dr. Alavi is from the Department of Dermatology, Mayo Clinic, Rochester, Minnesota. Drs. Chang and Fox are from the Department of Dermatology, School of Medicine, University of California San Francisco. Dr. Daveluy is from the School of Medicine, Wayne State University, Detroit, Michigan. Dr. DeNiro is from the Division of Dermatology, Department of Medicine, University of Washington, Seattle. Dr. Dewan is from Vanderbilt University Medical Center, Nashville, Tennessee. Drs. Eshaq and Manusco are from the Department of Dermatology, University of Michigan Medical School, Ann Arbor. Dr. Hsiao is from the Department of Dermatology, University of Southern California, Los Angeles. Dr. Kaffenberger is from the Department of Dermatology, Ohio State University, Columbus. Dr. Kirby is from the Department of Dermatology, Penn State Milton S. Hershey Medical Center, Pennsylvania, and Incyte Corporation, Wilmington, Delaware. Drs. Kroshinsky, Mostaghimi, and Porter are from the Department of Dermatology, Harvard Medical School, Boston, Massachusetts. Drs. Kroshinsky and Mostaghimi also are from the Department of Dermatology, Brigham & Women’s Hospital, Boston. Dr. Porter also is from the Department of Dermatology, Beth Israel Deaconess Medical Center, Boston. Dr. Ortega-Loayza is from the Department of Dermatology, Oregon Health & Science University, Portland. Dr. Micheletti is from the Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Nelson is from the Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Dr. Pasieka is from the Department of Dermatology and Medicine, Uniformed Services University, Bethesda, Maryland. Dr. Resnik is from the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Florida. Dr. Sayed is from the Department of Dermatology, University of North Carolina at Chapel Hill. Dr. Shi is from the Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock. Dr. Shields is from the Department of Dermatology, University of Wisconsin, Madison.

McKenzie Needham as well as Drs. Chang, DeNiro, Dewan, Eshaq, Kroshinsky, Manusco, and Pasieka report no conflicts of interest. Dr. Pichardo has been an advisor for Novartis and UCB. Dr. Alavi is a consultant for Almirall, Boehringer-Ingelheim, InflaRx, LEO Pharma, Novartis, and UCB; is on the board of editors for the Hidradenitis Suppurativa Foundation; has received a research grant from the National Institutes of Health; and has equity in Medical Dermatology. Dr. Daveluy is a speaker for AbbVie, Novartis, and UCB, and has received research grants from AbbVie, Novartis, Pfizer, Regeneron, Sanofi, and UCB. Dr. Fox is a co-founder of and holds equity in DermLab. Dr. Hsiao is on the Board of Directors for the Hidradenitis Suppurativa Foundation; is a speaker for AbbVie, Novartis, Regeneron, Sanofi, and UCB; has received research grants from Amgen, Boehringer-Ingelheim, and Incyte; and is an advisor for AbbVie, Aclaris, Boehringer-Ingelheim, Incyte, Novartis, and UCB. Dr. Kaffenberger is a consultant for ADC Therapeutics, Biogen, and Eli Lilly and Company; a speaker for Novartis and Novocure; and has received research grants from Biogen, InflaRx, Merck, and Target-Derm. Dr. Kirby is an employee of Incyte. Dr. Ortega-Loayza is an advisory board member and/or speaker for Biotech, Bristol Myers Squibb, Boehringer-Ingelheim, and Sanofi, and has received research grants and/or consulting fees from AbbVie, Boehringer-Ingelheim, Castle Biosciences, Clarivate, Corvus Pharmaceuticals, Eli Lilly and Company, Genentech, Guidepoint, Incyte, InflaRx, Janssen, National Institutes of Health, Otsuka, Pfizer, Sitala Bio Ltd, and TFS Health Science. Dr. Micheletti is a consultant for Vertex and has received research grants from Acelyrin, Amgen, Boehringer-Ingelheim, Cabaletta Bio, and InflaRx. Dr. Mostaghimi has received income from AbbVie, ASLAN, Boehringer-Ingelheim, Dermatheory, Digital Diagnostics, Eli Lilly and Company, Equillium, Figure 1 Inc, Hims & Hers Health, Inc, Legacy Healthcare, Olapex, Pfizer, and Sun Pharmaceuticals. Dr. Nelson is an advisory board member for and has received research grants from Boehringer-Ingelheim. Dr. Porter is a consultant for or has received research grants from AbbVie, Alumis, AnaptysBio, Avalo, Bayer, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, Moonlake Therapeutics, Novartis, Oasis Pharmaceuticals, Pfizer, Prometheus Laboratories, Regeneron, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, and UCB. Dr. Resnik serves or served as a speaker for AbbVie and Novartis. Dr. Sayed serves or served as an advisor, consultant, director, employee, investigator, officer, partner, speaker, or trustee for AbbVie, AstraZeneca, Chemocentryx, Incyte, InflaRx, Logical Images, Novartis, Sandoz, Sanofi, and UCB. Dr. Shi is on the Board of Directors for the Hidradenitis Suppurativa Foundation and is an advisor for the National Eczema Association; is a consultant, investigator, and/or speaker for AbbVie, Almirall, Altus Lab/cQuell, Alumis, Aristea Therapeutics, ASLAN, Bain Capital, BoehringerIngelheim, Burt’s Bees, Castle Biosciences, Dermira, Eli Lilly and Company, Galderma, Genentech, GpSkin, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, MYOR, Novartis, Pfizer, Polyfins Technology, Regeneron, Sanofi-Genzyme, Skin Actives Scientific, Sun Pharmaceuticals, Target Pharma Solutions, and UCB; has received research grants from Pfizer and Skin Actives Scientific; and is a stock shareholder in Learn Health. Dr. Shields is on the advisory board for Arcutis Therapeutics and has received income from UpToDate, Inc. Dr. Strowd is a speaker for and/or has received research grants or income from Galderma, Pfizer, Regeneron, and Sanofi. The opinions and assertions expressed herein are those of the author(s) and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences or the Department of Defense. This work was prepared by a military or civilian employee of the US Government as part of the individual’s official duties and therefore is in the public domain and does not possess copyright protection (public domain information may be freely distributed and copied; however, as a courtesy it is requested that the Uniformed Services University and the author be given an appropriate acknowledgment).

The eTables are available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Lindsay C. Strowd, MD ([email protected]).

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Author and Disclosure Information

McKenzie Needham and Drs. Pichardo and Strowd are from the Wake Forest University School of Medicine, Winston-Salem, North Carolina. Drs. Pichardo and Strowd also are from the Department of Dermatology, Atrium Health Wake Forest Baptist, Winston-Salem. Dr. Alavi is from the Department of Dermatology, Mayo Clinic, Rochester, Minnesota. Drs. Chang and Fox are from the Department of Dermatology, School of Medicine, University of California San Francisco. Dr. Daveluy is from the School of Medicine, Wayne State University, Detroit, Michigan. Dr. DeNiro is from the Division of Dermatology, Department of Medicine, University of Washington, Seattle. Dr. Dewan is from Vanderbilt University Medical Center, Nashville, Tennessee. Drs. Eshaq and Manusco are from the Department of Dermatology, University of Michigan Medical School, Ann Arbor. Dr. Hsiao is from the Department of Dermatology, University of Southern California, Los Angeles. Dr. Kaffenberger is from the Department of Dermatology, Ohio State University, Columbus. Dr. Kirby is from the Department of Dermatology, Penn State Milton S. Hershey Medical Center, Pennsylvania, and Incyte Corporation, Wilmington, Delaware. Drs. Kroshinsky, Mostaghimi, and Porter are from the Department of Dermatology, Harvard Medical School, Boston, Massachusetts. Drs. Kroshinsky and Mostaghimi also are from the Department of Dermatology, Brigham & Women’s Hospital, Boston. Dr. Porter also is from the Department of Dermatology, Beth Israel Deaconess Medical Center, Boston. Dr. Ortega-Loayza is from the Department of Dermatology, Oregon Health & Science University, Portland. Dr. Micheletti is from the Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Nelson is from the Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Dr. Pasieka is from the Department of Dermatology and Medicine, Uniformed Services University, Bethesda, Maryland. Dr. Resnik is from the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Florida. Dr. Sayed is from the Department of Dermatology, University of North Carolina at Chapel Hill. Dr. Shi is from the Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock. Dr. Shields is from the Department of Dermatology, University of Wisconsin, Madison.

McKenzie Needham as well as Drs. Chang, DeNiro, Dewan, Eshaq, Kroshinsky, Manusco, and Pasieka report no conflicts of interest. Dr. Pichardo has been an advisor for Novartis and UCB. Dr. Alavi is a consultant for Almirall, Boehringer-Ingelheim, InflaRx, LEO Pharma, Novartis, and UCB; is on the board of editors for the Hidradenitis Suppurativa Foundation; has received a research grant from the National Institutes of Health; and has equity in Medical Dermatology. Dr. Daveluy is a speaker for AbbVie, Novartis, and UCB, and has received research grants from AbbVie, Novartis, Pfizer, Regeneron, Sanofi, and UCB. Dr. Fox is a co-founder of and holds equity in DermLab. Dr. Hsiao is on the Board of Directors for the Hidradenitis Suppurativa Foundation; is a speaker for AbbVie, Novartis, Regeneron, Sanofi, and UCB; has received research grants from Amgen, Boehringer-Ingelheim, and Incyte; and is an advisor for AbbVie, Aclaris, Boehringer-Ingelheim, Incyte, Novartis, and UCB. Dr. Kaffenberger is a consultant for ADC Therapeutics, Biogen, and Eli Lilly and Company; a speaker for Novartis and Novocure; and has received research grants from Biogen, InflaRx, Merck, and Target-Derm. Dr. Kirby is an employee of Incyte. Dr. Ortega-Loayza is an advisory board member and/or speaker for Biotech, Bristol Myers Squibb, Boehringer-Ingelheim, and Sanofi, and has received research grants and/or consulting fees from AbbVie, Boehringer-Ingelheim, Castle Biosciences, Clarivate, Corvus Pharmaceuticals, Eli Lilly and Company, Genentech, Guidepoint, Incyte, InflaRx, Janssen, National Institutes of Health, Otsuka, Pfizer, Sitala Bio Ltd, and TFS Health Science. Dr. Micheletti is a consultant for Vertex and has received research grants from Acelyrin, Amgen, Boehringer-Ingelheim, Cabaletta Bio, and InflaRx. Dr. Mostaghimi has received income from AbbVie, ASLAN, Boehringer-Ingelheim, Dermatheory, Digital Diagnostics, Eli Lilly and Company, Equillium, Figure 1 Inc, Hims & Hers Health, Inc, Legacy Healthcare, Olapex, Pfizer, and Sun Pharmaceuticals. Dr. Nelson is an advisory board member for and has received research grants from Boehringer-Ingelheim. Dr. Porter is a consultant for or has received research grants from AbbVie, Alumis, AnaptysBio, Avalo, Bayer, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, Moonlake Therapeutics, Novartis, Oasis Pharmaceuticals, Pfizer, Prometheus Laboratories, Regeneron, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, and UCB. Dr. Resnik serves or served as a speaker for AbbVie and Novartis. Dr. Sayed serves or served as an advisor, consultant, director, employee, investigator, officer, partner, speaker, or trustee for AbbVie, AstraZeneca, Chemocentryx, Incyte, InflaRx, Logical Images, Novartis, Sandoz, Sanofi, and UCB. Dr. Shi is on the Board of Directors for the Hidradenitis Suppurativa Foundation and is an advisor for the National Eczema Association; is a consultant, investigator, and/or speaker for AbbVie, Almirall, Altus Lab/cQuell, Alumis, Aristea Therapeutics, ASLAN, Bain Capital, BoehringerIngelheim, Burt’s Bees, Castle Biosciences, Dermira, Eli Lilly and Company, Galderma, Genentech, GpSkin, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, MYOR, Novartis, Pfizer, Polyfins Technology, Regeneron, Sanofi-Genzyme, Skin Actives Scientific, Sun Pharmaceuticals, Target Pharma Solutions, and UCB; has received research grants from Pfizer and Skin Actives Scientific; and is a stock shareholder in Learn Health. Dr. Shields is on the advisory board for Arcutis Therapeutics and has received income from UpToDate, Inc. Dr. Strowd is a speaker for and/or has received research grants or income from Galderma, Pfizer, Regeneron, and Sanofi. The opinions and assertions expressed herein are those of the author(s) and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences or the Department of Defense. This work was prepared by a military or civilian employee of the US Government as part of the individual’s official duties and therefore is in the public domain and does not possess copyright protection (public domain information may be freely distributed and copied; however, as a courtesy it is requested that the Uniformed Services University and the author be given an appropriate acknowledgment).

The eTables are available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Lindsay C. Strowd, MD ([email protected]).

Author and Disclosure Information

McKenzie Needham and Drs. Pichardo and Strowd are from the Wake Forest University School of Medicine, Winston-Salem, North Carolina. Drs. Pichardo and Strowd also are from the Department of Dermatology, Atrium Health Wake Forest Baptist, Winston-Salem. Dr. Alavi is from the Department of Dermatology, Mayo Clinic, Rochester, Minnesota. Drs. Chang and Fox are from the Department of Dermatology, School of Medicine, University of California San Francisco. Dr. Daveluy is from the School of Medicine, Wayne State University, Detroit, Michigan. Dr. DeNiro is from the Division of Dermatology, Department of Medicine, University of Washington, Seattle. Dr. Dewan is from Vanderbilt University Medical Center, Nashville, Tennessee. Drs. Eshaq and Manusco are from the Department of Dermatology, University of Michigan Medical School, Ann Arbor. Dr. Hsiao is from the Department of Dermatology, University of Southern California, Los Angeles. Dr. Kaffenberger is from the Department of Dermatology, Ohio State University, Columbus. Dr. Kirby is from the Department of Dermatology, Penn State Milton S. Hershey Medical Center, Pennsylvania, and Incyte Corporation, Wilmington, Delaware. Drs. Kroshinsky, Mostaghimi, and Porter are from the Department of Dermatology, Harvard Medical School, Boston, Massachusetts. Drs. Kroshinsky and Mostaghimi also are from the Department of Dermatology, Brigham & Women’s Hospital, Boston. Dr. Porter also is from the Department of Dermatology, Beth Israel Deaconess Medical Center, Boston. Dr. Ortega-Loayza is from the Department of Dermatology, Oregon Health & Science University, Portland. Dr. Micheletti is from the Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Nelson is from the Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Dr. Pasieka is from the Department of Dermatology and Medicine, Uniformed Services University, Bethesda, Maryland. Dr. Resnik is from the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Florida. Dr. Sayed is from the Department of Dermatology, University of North Carolina at Chapel Hill. Dr. Shi is from the Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock. Dr. Shields is from the Department of Dermatology, University of Wisconsin, Madison.

McKenzie Needham as well as Drs. Chang, DeNiro, Dewan, Eshaq, Kroshinsky, Manusco, and Pasieka report no conflicts of interest. Dr. Pichardo has been an advisor for Novartis and UCB. Dr. Alavi is a consultant for Almirall, Boehringer-Ingelheim, InflaRx, LEO Pharma, Novartis, and UCB; is on the board of editors for the Hidradenitis Suppurativa Foundation; has received a research grant from the National Institutes of Health; and has equity in Medical Dermatology. Dr. Daveluy is a speaker for AbbVie, Novartis, and UCB, and has received research grants from AbbVie, Novartis, Pfizer, Regeneron, Sanofi, and UCB. Dr. Fox is a co-founder of and holds equity in DermLab. Dr. Hsiao is on the Board of Directors for the Hidradenitis Suppurativa Foundation; is a speaker for AbbVie, Novartis, Regeneron, Sanofi, and UCB; has received research grants from Amgen, Boehringer-Ingelheim, and Incyte; and is an advisor for AbbVie, Aclaris, Boehringer-Ingelheim, Incyte, Novartis, and UCB. Dr. Kaffenberger is a consultant for ADC Therapeutics, Biogen, and Eli Lilly and Company; a speaker for Novartis and Novocure; and has received research grants from Biogen, InflaRx, Merck, and Target-Derm. Dr. Kirby is an employee of Incyte. Dr. Ortega-Loayza is an advisory board member and/or speaker for Biotech, Bristol Myers Squibb, Boehringer-Ingelheim, and Sanofi, and has received research grants and/or consulting fees from AbbVie, Boehringer-Ingelheim, Castle Biosciences, Clarivate, Corvus Pharmaceuticals, Eli Lilly and Company, Genentech, Guidepoint, Incyte, InflaRx, Janssen, National Institutes of Health, Otsuka, Pfizer, Sitala Bio Ltd, and TFS Health Science. Dr. Micheletti is a consultant for Vertex and has received research grants from Acelyrin, Amgen, Boehringer-Ingelheim, Cabaletta Bio, and InflaRx. Dr. Mostaghimi has received income from AbbVie, ASLAN, Boehringer-Ingelheim, Dermatheory, Digital Diagnostics, Eli Lilly and Company, Equillium, Figure 1 Inc, Hims & Hers Health, Inc, Legacy Healthcare, Olapex, Pfizer, and Sun Pharmaceuticals. Dr. Nelson is an advisory board member for and has received research grants from Boehringer-Ingelheim. Dr. Porter is a consultant for or has received research grants from AbbVie, Alumis, AnaptysBio, Avalo, Bayer, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, Moonlake Therapeutics, Novartis, Oasis Pharmaceuticals, Pfizer, Prometheus Laboratories, Regeneron, Sanofi, Sonoma Biotherapeutics, Trifecta Clinical, and UCB. Dr. Resnik serves or served as a speaker for AbbVie and Novartis. Dr. Sayed serves or served as an advisor, consultant, director, employee, investigator, officer, partner, speaker, or trustee for AbbVie, AstraZeneca, Chemocentryx, Incyte, InflaRx, Logical Images, Novartis, Sandoz, Sanofi, and UCB. Dr. Shi is on the Board of Directors for the Hidradenitis Suppurativa Foundation and is an advisor for the National Eczema Association; is a consultant, investigator, and/or speaker for AbbVie, Almirall, Altus Lab/cQuell, Alumis, Aristea Therapeutics, ASLAN, Bain Capital, BoehringerIngelheim, Burt’s Bees, Castle Biosciences, Dermira, Eli Lilly and Company, Galderma, Genentech, GpSkin, Incyte, Kiniksa, LEO Pharma, Menlo Therapeutics, MYOR, Novartis, Pfizer, Polyfins Technology, Regeneron, Sanofi-Genzyme, Skin Actives Scientific, Sun Pharmaceuticals, Target Pharma Solutions, and UCB; has received research grants from Pfizer and Skin Actives Scientific; and is a stock shareholder in Learn Health. Dr. Shields is on the advisory board for Arcutis Therapeutics and has received income from UpToDate, Inc. Dr. Strowd is a speaker for and/or has received research grants or income from Galderma, Pfizer, Regeneron, and Sanofi. The opinions and assertions expressed herein are those of the author(s) and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences or the Department of Defense. This work was prepared by a military or civilian employee of the US Government as part of the individual’s official duties and therefore is in the public domain and does not possess copyright protection (public domain information may be freely distributed and copied; however, as a courtesy it is requested that the Uniformed Services University and the author be given an appropriate acknowledgment).

The eTables are available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Lindsay C. Strowd, MD ([email protected]).

Article PDF
Article PDF

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects approximately 0.1% of the US population.1,2 Severe disease or HS flares can lead patients to seek care through the emergency department (ED), with some requiring inpatient admission. 3 Inpatient hospitalization of patients with HS has increased over the last 2 decades, and patients with HS utilize emergency and inpatient care more frequently than those with other dermatologic conditions.4,5 Minority patients and those of lower socioeconomic status are more likely to present to the ED for HS management due to limited access to care and other existing comorbid conditions. 4 In a 2022 study of the Nationwide Readmissions Database, the authors looked at hospital readmission rates of patients with HS compared with those with heart failure—both patient populations with chronic debilitating conditions. Results indicated that the hospital readmission rates for patients with HS surpassed those of patients with heart failure for that year, highlighting the need for improved inpatient management of HS.6

Patients with HS present to the ED with severe pain, fever, wound care, or the need for surgical intervention. The ED and inpatient hospital setting are locations in which physicians may not be as familiar with the diagnosis or treatment of HS, specifically flares or severe disease. 7 The inpatient care setting provides access to certain resources that can be challenging to obtain in the outpatient clinical setting, such as social workers and pain specialists, but also can prove challenging in obtaining other resources for HS management, such as advanced medical therapies. Given the increase in hospital- based care for HS and lack of widespread inpatient access to dermatology and HS experts, consensus recommendations for management of HS in the acute hospital setting would be beneficial. In our study, we sought to generate a collection of expert consensus statements providers can refer to when managing patients with HS in the inpatient setting.

Methods

The study team at the Wake Forest University School of Medicine (Winston-Salem, North Carolina)(M.N., R.P., L.C.S.) developed an initial set of consensus statements based on current published HS treatment guidelines,8,9 publications on management of inpatient HS,3 published supportive care guidelines for Stevens-Johnson syndrome, 10 and personal clinical experience in managing inpatient HS, which resulted in 50 statements organized into the following categories: overall care, wound care, genital care, pain management, infection control, medical management, surgical management, nutrition, and transitional care guidelines. This study was approved by the Wake Forest University institutional review board (IRB00084257).

Participant Recruitment—Dermatologists were identified for participation in the study based on membership in the Society of Dermatology Hospitalists and the Hidradenitis Suppurativa Foundation or authorship of publications relevant to HS or inpatient dermatology. Dermatologists from larger academic institutions with HS specialty clinics and inpatient dermatology services also were identified. Participants were invited via email and could suggest other experts for inclusion. A total of 31 dermatologists were invited to participate in the study, with 26 agreeing to participate. All participating dermatologists were practicing in the United States.

Delphi Study—In the first round of the Delphi study, the participants were sent an online survey via REDCap in which they were asked to rank the appropriateness of each of the proposed 50 guideline statements on a scale of 1 (very inappropriate) to 9 (very appropriate). Participants also were able to provide commentary and feedback on each of the statements. Survey results were analyzed using the RAND/ UCLA Appropriateness Method.11 For each statement, the median rating for appropriateness, interpercentile range (IPR), IPR adjusted for symmetry, and disagreement index (DI) were calculated (DI=IPR/IPR adjusted for symmetry). The 30th and 70th percentiles were used in the DI calculation as the upper and lower limits, respectively. A median rating for appropriateness of 1.0 to 3.9 was considered “inappropriate,” 4.0 to 6.9 was considered “uncertain appropriateness,” and 7.0 to 9.0 was “appropriate.” A DI value greater than or equal to 1 indicated a lack of consensus regarding the appropriateness of the statement. Following each round, participants received a copy of their responses along with the group median rank of each statement. Statements that did not reach consensus in the first Delphi round were revised based on feedback received by the participants, and a second survey with 14 statements was sent via REDCap 2 weeks later. The RAND/UCLA Appropriateness Method also was applied to this second Delphi round. After the second survey, participants received a copy of anonymized comments regarding the consensus statements and were allowed to provide additional final commentary to be included in the discussion of these recommendations.

Results

Twenty-six dermatologists completed the first-round survey, and 24 participants completed the second-round survey. All participants self-identified as having expertise in either HS (n=22 [85%]) or inpatient dermatology (n=17 [65%]), and 13 (50%) participants self-identified as experts in both HS and inpatient dermatology. All participants, except 1, were affiliated with an academic health system with inpatient dermatology services. The average length of time in practice as a dermatologist was 10 years (median, 9 years [range, 3–27 years]).

Of the 50 initial proposed consensus statements, 26 (52%) achieved consensus after the first round; 21 statements revealed DI calculations that did not achieve consensus. Two statements achieved consensus but received median ratings for appropriateness, indicating uncertain appropriateness; because of this, 1 statement was removed and 1 was revised based on participant feedback, resulting in 13 revised statements (eTable 1). Controversial topics in the consensus process included obtaining wound cultures and meaningful culture data interpretation, use of specific biologic medications in the inpatient setting, and use of intravenous ertapenem. Participant responses to these topics are discussed in detail below. Of these secondround statements, all achieved consensus. The final set of consensus statements can be found in eTable 2.

Comment

Our Delphi consensus study combined the expertise of both dermatologists who care for patients with HS and those with inpatient dermatology experience to produce a set of recommendations for the management of HS in the hospital care setting. A strength of this study is inclusion of many national leaders in both HS and inpatient dermatology, with some participants having developed the previously published HS treatment guidelines and others having participated in inpatient dermatology Delphi studies.8-10 The expertise is further strengthened by the geographically diverse institutional representation within the United States.

The final consensus recommendations included 40 statements covering a range of patient care issues, including use of appropriate inpatient subspecialists (care team), supportive care measures (wound care, pain control, genital care), disease-oriented treatment (medical management, surgical management), inpatient complications (infection control, nutrition), and successful transition back to outpatient management (transitional care). These recommendations are meant to serve as a resource for providers to consider when taking care of inpatient HS flares, recognizing that the complexity and individual circumstances of each patient are unique.

Delphi Consensus Recommendations Compared to Prior Guidelines—Several recommendations in the current study align with the previously published North American clinical management guidelines for HS.8,9 Our recommendations agree with prior guidelines on the importance of disease staging and pain assessment using validated assessment tools as well as screening for HS comorbidities. There also is agreement in the potential benefit of involving pain specialists in the development of a comprehensive pain management plan. The inpatient care setting provides a unique opportunity to engage multiple specialists and collaborate on patient care in a timely manner. Our recommendations regarding surgical care also align with established guidelines in recommending incision and drainage as an acute bedside procedure best utilized for symptom relief in inflamed abscesses and relegating most other surgical management to the outpatient setting. Wound care recommendations also are similar, with our expert participants agreeing on individualizing dressing choices based on wound characteristics. A benefit of inpatient wound care is access to skilled nursing for dressing changes and potentially improved access to more sophisticated dressing materials. Our recommendations differ from the prior guidelines in our focus on severe HS, HS flares, and HS complications, which constitute the majority of inpatient disease management. We provide additional guidance on management of secondary infections, perianal fistulous disease, and importantly transitional care to optimize discharge planning.

Differing Opinions in Our Analysis—Despite the success of our Delphi consensus process, there were some differing opinions regarding certain aspects of inpatient HS management, which is to be expected given the lack of strong evidence-based research to support some of the recommended practices. There were differing opinions on the utility of wound culture data, with some participants feeling culture data could help with antibiotic susceptibility and resistance patterns, while others felt wound cultures represent bacterial colonization or biofilm formation.

Initial consensus statements in the first Delphi round were created for individual biologic medications but did not achieve consensus, and feedback on the use of biologics in the inpatient environment was mixed, largely due to logistic and insurance issues. Many participants felt biologic medication cost, difficulty obtaining inpatient reimbursement, health care resource utilization, and availability of biologics in different hospital systems prevented recommending the use of specific biologics during hospitalization. The one exception was in the case of a hospitalized patient who was already receiving infliximab for HS: there was consensus on ensuring the patient dosing was maximized, if appropriate, to 10 mg/kg.12 Ertapenem use also was controversial, with some participants using it as a bridge therapy to either outpatient biologic use or surgery, while others felt it was onerous and difficult to establish reliable access to secure intravenous administration and regular dosing once the patient left the inpatient setting.13 Others said they have experienced objections from infectious disease colleagues on the use of intravenous antibiotics, citing antibiotic stewardship concerns.

Patient Care in the Inpatient Setting—Prior literature suggests patients admitted as inpatients for HS tend to be of lower socioeconomic status and are admitted to larger urban teaching hospitals.14,15 Patients with lower socioeconomic status have increased difficulty accessing health care resources; therefore, inpatient admission serves as an opportunity to provide a holistic HS assessment and coordinate resources for chronic outpatient management.

Study Limitations—This Delphi consensus study has some limitations. The existing literature on inpatient management of HS is limited, challenging our ability to assess the extent to which these published recommendations are already being implemented. Additionally, the study included HS and inpatient dermatology experts from the United States, which means the recommendations may not be generalizable to other countries. Most participants practiced dermatology at large tertiary care academic medical centers, which may limit the ability to implement recommendations in all US inpatient care settings such as small community-based hospitals; however, many of the supportive care guidelines such as pain control, wound care, nutritional support, and social work should be achievable in most inpatient care settings.

Conclusion

Given the increase in inpatient and ED health care utilization for HS, there is an urgent need for expert consensus recommendations on inpatient management of this unique patient population, which requires complex multidisciplinary care. Our recommendations are a resource for providers to utilize and potentially improve the standard of care we provide these patients.

Acknowledgment—We thank the Wake Forest University Clinical and Translational Science Institute (Winston- Salem, North Carolina) for providing statistical help.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects approximately 0.1% of the US population.1,2 Severe disease or HS flares can lead patients to seek care through the emergency department (ED), with some requiring inpatient admission. 3 Inpatient hospitalization of patients with HS has increased over the last 2 decades, and patients with HS utilize emergency and inpatient care more frequently than those with other dermatologic conditions.4,5 Minority patients and those of lower socioeconomic status are more likely to present to the ED for HS management due to limited access to care and other existing comorbid conditions. 4 In a 2022 study of the Nationwide Readmissions Database, the authors looked at hospital readmission rates of patients with HS compared with those with heart failure—both patient populations with chronic debilitating conditions. Results indicated that the hospital readmission rates for patients with HS surpassed those of patients with heart failure for that year, highlighting the need for improved inpatient management of HS.6

Patients with HS present to the ED with severe pain, fever, wound care, or the need for surgical intervention. The ED and inpatient hospital setting are locations in which physicians may not be as familiar with the diagnosis or treatment of HS, specifically flares or severe disease. 7 The inpatient care setting provides access to certain resources that can be challenging to obtain in the outpatient clinical setting, such as social workers and pain specialists, but also can prove challenging in obtaining other resources for HS management, such as advanced medical therapies. Given the increase in hospital- based care for HS and lack of widespread inpatient access to dermatology and HS experts, consensus recommendations for management of HS in the acute hospital setting would be beneficial. In our study, we sought to generate a collection of expert consensus statements providers can refer to when managing patients with HS in the inpatient setting.

Methods

The study team at the Wake Forest University School of Medicine (Winston-Salem, North Carolina)(M.N., R.P., L.C.S.) developed an initial set of consensus statements based on current published HS treatment guidelines,8,9 publications on management of inpatient HS,3 published supportive care guidelines for Stevens-Johnson syndrome, 10 and personal clinical experience in managing inpatient HS, which resulted in 50 statements organized into the following categories: overall care, wound care, genital care, pain management, infection control, medical management, surgical management, nutrition, and transitional care guidelines. This study was approved by the Wake Forest University institutional review board (IRB00084257).

Participant Recruitment—Dermatologists were identified for participation in the study based on membership in the Society of Dermatology Hospitalists and the Hidradenitis Suppurativa Foundation or authorship of publications relevant to HS or inpatient dermatology. Dermatologists from larger academic institutions with HS specialty clinics and inpatient dermatology services also were identified. Participants were invited via email and could suggest other experts for inclusion. A total of 31 dermatologists were invited to participate in the study, with 26 agreeing to participate. All participating dermatologists were practicing in the United States.

Delphi Study—In the first round of the Delphi study, the participants were sent an online survey via REDCap in which they were asked to rank the appropriateness of each of the proposed 50 guideline statements on a scale of 1 (very inappropriate) to 9 (very appropriate). Participants also were able to provide commentary and feedback on each of the statements. Survey results were analyzed using the RAND/ UCLA Appropriateness Method.11 For each statement, the median rating for appropriateness, interpercentile range (IPR), IPR adjusted for symmetry, and disagreement index (DI) were calculated (DI=IPR/IPR adjusted for symmetry). The 30th and 70th percentiles were used in the DI calculation as the upper and lower limits, respectively. A median rating for appropriateness of 1.0 to 3.9 was considered “inappropriate,” 4.0 to 6.9 was considered “uncertain appropriateness,” and 7.0 to 9.0 was “appropriate.” A DI value greater than or equal to 1 indicated a lack of consensus regarding the appropriateness of the statement. Following each round, participants received a copy of their responses along with the group median rank of each statement. Statements that did not reach consensus in the first Delphi round were revised based on feedback received by the participants, and a second survey with 14 statements was sent via REDCap 2 weeks later. The RAND/UCLA Appropriateness Method also was applied to this second Delphi round. After the second survey, participants received a copy of anonymized comments regarding the consensus statements and were allowed to provide additional final commentary to be included in the discussion of these recommendations.

Results

Twenty-six dermatologists completed the first-round survey, and 24 participants completed the second-round survey. All participants self-identified as having expertise in either HS (n=22 [85%]) or inpatient dermatology (n=17 [65%]), and 13 (50%) participants self-identified as experts in both HS and inpatient dermatology. All participants, except 1, were affiliated with an academic health system with inpatient dermatology services. The average length of time in practice as a dermatologist was 10 years (median, 9 years [range, 3–27 years]).

Of the 50 initial proposed consensus statements, 26 (52%) achieved consensus after the first round; 21 statements revealed DI calculations that did not achieve consensus. Two statements achieved consensus but received median ratings for appropriateness, indicating uncertain appropriateness; because of this, 1 statement was removed and 1 was revised based on participant feedback, resulting in 13 revised statements (eTable 1). Controversial topics in the consensus process included obtaining wound cultures and meaningful culture data interpretation, use of specific biologic medications in the inpatient setting, and use of intravenous ertapenem. Participant responses to these topics are discussed in detail below. Of these secondround statements, all achieved consensus. The final set of consensus statements can be found in eTable 2.

Comment

Our Delphi consensus study combined the expertise of both dermatologists who care for patients with HS and those with inpatient dermatology experience to produce a set of recommendations for the management of HS in the hospital care setting. A strength of this study is inclusion of many national leaders in both HS and inpatient dermatology, with some participants having developed the previously published HS treatment guidelines and others having participated in inpatient dermatology Delphi studies.8-10 The expertise is further strengthened by the geographically diverse institutional representation within the United States.

The final consensus recommendations included 40 statements covering a range of patient care issues, including use of appropriate inpatient subspecialists (care team), supportive care measures (wound care, pain control, genital care), disease-oriented treatment (medical management, surgical management), inpatient complications (infection control, nutrition), and successful transition back to outpatient management (transitional care). These recommendations are meant to serve as a resource for providers to consider when taking care of inpatient HS flares, recognizing that the complexity and individual circumstances of each patient are unique.

Delphi Consensus Recommendations Compared to Prior Guidelines—Several recommendations in the current study align with the previously published North American clinical management guidelines for HS.8,9 Our recommendations agree with prior guidelines on the importance of disease staging and pain assessment using validated assessment tools as well as screening for HS comorbidities. There also is agreement in the potential benefit of involving pain specialists in the development of a comprehensive pain management plan. The inpatient care setting provides a unique opportunity to engage multiple specialists and collaborate on patient care in a timely manner. Our recommendations regarding surgical care also align with established guidelines in recommending incision and drainage as an acute bedside procedure best utilized for symptom relief in inflamed abscesses and relegating most other surgical management to the outpatient setting. Wound care recommendations also are similar, with our expert participants agreeing on individualizing dressing choices based on wound characteristics. A benefit of inpatient wound care is access to skilled nursing for dressing changes and potentially improved access to more sophisticated dressing materials. Our recommendations differ from the prior guidelines in our focus on severe HS, HS flares, and HS complications, which constitute the majority of inpatient disease management. We provide additional guidance on management of secondary infections, perianal fistulous disease, and importantly transitional care to optimize discharge planning.

Differing Opinions in Our Analysis—Despite the success of our Delphi consensus process, there were some differing opinions regarding certain aspects of inpatient HS management, which is to be expected given the lack of strong evidence-based research to support some of the recommended practices. There were differing opinions on the utility of wound culture data, with some participants feeling culture data could help with antibiotic susceptibility and resistance patterns, while others felt wound cultures represent bacterial colonization or biofilm formation.

Initial consensus statements in the first Delphi round were created for individual biologic medications but did not achieve consensus, and feedback on the use of biologics in the inpatient environment was mixed, largely due to logistic and insurance issues. Many participants felt biologic medication cost, difficulty obtaining inpatient reimbursement, health care resource utilization, and availability of biologics in different hospital systems prevented recommending the use of specific biologics during hospitalization. The one exception was in the case of a hospitalized patient who was already receiving infliximab for HS: there was consensus on ensuring the patient dosing was maximized, if appropriate, to 10 mg/kg.12 Ertapenem use also was controversial, with some participants using it as a bridge therapy to either outpatient biologic use or surgery, while others felt it was onerous and difficult to establish reliable access to secure intravenous administration and regular dosing once the patient left the inpatient setting.13 Others said they have experienced objections from infectious disease colleagues on the use of intravenous antibiotics, citing antibiotic stewardship concerns.

Patient Care in the Inpatient Setting—Prior literature suggests patients admitted as inpatients for HS tend to be of lower socioeconomic status and are admitted to larger urban teaching hospitals.14,15 Patients with lower socioeconomic status have increased difficulty accessing health care resources; therefore, inpatient admission serves as an opportunity to provide a holistic HS assessment and coordinate resources for chronic outpatient management.

Study Limitations—This Delphi consensus study has some limitations. The existing literature on inpatient management of HS is limited, challenging our ability to assess the extent to which these published recommendations are already being implemented. Additionally, the study included HS and inpatient dermatology experts from the United States, which means the recommendations may not be generalizable to other countries. Most participants practiced dermatology at large tertiary care academic medical centers, which may limit the ability to implement recommendations in all US inpatient care settings such as small community-based hospitals; however, many of the supportive care guidelines such as pain control, wound care, nutritional support, and social work should be achievable in most inpatient care settings.

Conclusion

Given the increase in inpatient and ED health care utilization for HS, there is an urgent need for expert consensus recommendations on inpatient management of this unique patient population, which requires complex multidisciplinary care. Our recommendations are a resource for providers to utilize and potentially improve the standard of care we provide these patients.

Acknowledgment—We thank the Wake Forest University Clinical and Translational Science Institute (Winston- Salem, North Carolina) for providing statistical help.

References
  1. Garg A, Kirby JS, Lavian J, et al. Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States. JAMA Dermatol. 2017;153:760-764.
  2. Ingram JR. The epidemiology of hidradenitis suppurativa. Br J Dermatol. 2020;183:990-998. doi:10.1111/bjd.19435
  3. Charrow A, Savage KT, Flood K, et al. Hidradenitis suppurativa for the dermatologic hospitalist. Cutis. 2019;104:276-280.
  4. Anzaldi L, Perkins JA, Byrd AS, et al. Characterizing inpatient hospitalizations for hidradenitis suppurativa in the United States. J Am Acad Dermatol. 2020;82:510-513. doi:10.1016/j.jaad.2019.09.019
  5. Khalsa A, Liu G, Kirby JS. Increased utilization of emergency department and inpatient care by patients with hidradenitis suppurativa. J Am Acad Dermatol. 2015;73:609-614. doi:10.1016/j.jaad.2015.06.053
  6. Edigin E, Kaul S, Eseaton PO, et al. At 180 days hidradenitis suppurativa readmission rate is comparable to heart failure: analysis of the nationwide readmissions database. J Am Acad Dermatol. 2022;87:188-192. doi:10.1016/j.jaad.2021.06.894
  7. Kirby JS, Miller JJ, Adams DR, et al. Health care utilization patterns and costs for patients with hidradenitis suppurativa. JAMA Dermatol. 2014;150:937-944. doi:10.1001/jamadermatol.2014.691
  8. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part I: diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019;81:76-90. doi:10.1016/j .jaad.2019.02.067
  9. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101. doi:10.1016/j.jaad.2019.02.068
  10. Seminario-Vidal L, Kroshinsky D, Malachowski SJ, et al. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020;82:1553-1567. doi:10.1016/j .jaad.2020.02.066
  11. Fitch K, Bernstein SJ, Burnand B, et al. The RAND/UCLA Appropriateness Method: User’s Manual. Rand; 2001.
  12. Oskardmay AN, Miles JA, Sayed CJ. Determining the optimal dose of infliximab for treatment of hidradenitis suppurativa. J Am Acad Dermatol. 2019;81:702-708. doi:10.1016/j.jaad.2019.05.022
  13. Join-Lambert O, Coignard-Biehler H, Jais JP, et al. Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients. J Antimicrob Chemother. 2016;71:513-520. doi:10.1093/jac/dkv361
  14. Khanna R, Whang KA, Huang AH, et al. Inpatient burden of hidradenitis suppurativa in the United States: analysis of the 2016 National Inpatient Sample. J Dermatolog Treat. 2022;33:1150-1152. doi:10.1080/09 546634.2020.1773380
  15. Patel A, Patel A, Solanki D, et al. Hidradenitis suppurativa in the United States: insights from the national inpatient sample (2008-2017) on contemporary trends in demographics, hospitalization rates, chronic comorbid conditions, and mortality. Cureus. 2022;14:E24755. doi:10.7759/cureus.24755
References
  1. Garg A, Kirby JS, Lavian J, et al. Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States. JAMA Dermatol. 2017;153:760-764.
  2. Ingram JR. The epidemiology of hidradenitis suppurativa. Br J Dermatol. 2020;183:990-998. doi:10.1111/bjd.19435
  3. Charrow A, Savage KT, Flood K, et al. Hidradenitis suppurativa for the dermatologic hospitalist. Cutis. 2019;104:276-280.
  4. Anzaldi L, Perkins JA, Byrd AS, et al. Characterizing inpatient hospitalizations for hidradenitis suppurativa in the United States. J Am Acad Dermatol. 2020;82:510-513. doi:10.1016/j.jaad.2019.09.019
  5. Khalsa A, Liu G, Kirby JS. Increased utilization of emergency department and inpatient care by patients with hidradenitis suppurativa. J Am Acad Dermatol. 2015;73:609-614. doi:10.1016/j.jaad.2015.06.053
  6. Edigin E, Kaul S, Eseaton PO, et al. At 180 days hidradenitis suppurativa readmission rate is comparable to heart failure: analysis of the nationwide readmissions database. J Am Acad Dermatol. 2022;87:188-192. doi:10.1016/j.jaad.2021.06.894
  7. Kirby JS, Miller JJ, Adams DR, et al. Health care utilization patterns and costs for patients with hidradenitis suppurativa. JAMA Dermatol. 2014;150:937-944. doi:10.1001/jamadermatol.2014.691
  8. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part I: diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol. 2019;81:76-90. doi:10.1016/j .jaad.2019.02.067
  9. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019;81:91-101. doi:10.1016/j.jaad.2019.02.068
  10. Seminario-Vidal L, Kroshinsky D, Malachowski SJ, et al. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol. 2020;82:1553-1567. doi:10.1016/j .jaad.2020.02.066
  11. Fitch K, Bernstein SJ, Burnand B, et al. The RAND/UCLA Appropriateness Method: User’s Manual. Rand; 2001.
  12. Oskardmay AN, Miles JA, Sayed CJ. Determining the optimal dose of infliximab for treatment of hidradenitis suppurativa. J Am Acad Dermatol. 2019;81:702-708. doi:10.1016/j.jaad.2019.05.022
  13. Join-Lambert O, Coignard-Biehler H, Jais JP, et al. Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients. J Antimicrob Chemother. 2016;71:513-520. doi:10.1093/jac/dkv361
  14. Khanna R, Whang KA, Huang AH, et al. Inpatient burden of hidradenitis suppurativa in the United States: analysis of the 2016 National Inpatient Sample. J Dermatolog Treat. 2022;33:1150-1152. doi:10.1080/09 546634.2020.1773380
  15. Patel A, Patel A, Solanki D, et al. Hidradenitis suppurativa in the United States: insights from the national inpatient sample (2008-2017) on contemporary trends in demographics, hospitalization rates, chronic comorbid conditions, and mortality. Cureus. 2022;14:E24755. doi:10.7759/cureus.24755
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Practice Points

  • Given the increase in hospital-based care for hidradenitis suppurativa (HS) and the lack of widespread inpatient access to dermatology and HS experts, consensus recommendations for management of HS in the acute hospital setting would be beneficial.
  • Our Delphi study yielded 40 statements that reached consensus covering a range of patient care issues (eg, appropriate inpatient subspecialists [care team]), supportive care measures (wound care, pain control, genital care), disease-oriented treatment (medical management, surgical management), inpatient complications (infection control, nutrition), and successful transition to outpatient management (transitional care).
  • These recommendations serve as an important resource for providers caring for inpatients with HS and represent a successful collaboration between inpatient dermatology and HS experts.
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Targeting JAK Inhibitors in Severe Alopecia Areata

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Targeting JAK Inhibitors in Severe Alopecia Areata

Alopecia areata (AA) is an autoimmune disease that affects 2% of the population. Janus kinase (JAK) signaling has been shown to improve outcomes for many patients with severe AA, as outlined by Dr Brittany Craiglow, associate professor adjunct, Yale School of Medicine, New Haven, Connecticut.

Dr Craiglow reports that in AA, hair loss can be caused by key cytokines, including interleukin 15 and interferon gamma. These cytokines use the JAK-STAT pathway to transmit their signal. JAK inhibitors, which interfere with that pathway, are showing to be an effective treatment that can lead to hair growth.

Two JAK inhibitors have received US Food and Drug Administration approval for treatment of severe AA. Oral JAK1/2 inhibitor baricitinib has been approved for patients aged 18 years or older. The oral JAK3 inhibitor ritlecitinib has been approved for patients aged 12 years or older.

Dr Craiglow looks at clinical trials involving these JAK inhibitors. The results show that patients are more likely to respond to treatment earlier in the disease process. The study also found that patients with less severe hair loss (50%-94%) respond better than did those with severe hair loss.

Finally, Dr Craiglow explores the topic of JAK inhibitor selection. She notes that different medications will hit different JAK proteins, the failure of one JAK inhibitor does not always predict failure of another. Dr Craiglow points to current efficacy of these targeted therapies and expresses optimism about the future of personalized medicine in treating patients with severe AA.

--

Brittany Craiglow, MD, Associate Professor Adjunct, Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut

Brittany Craiglow, MD, has disclosed the following relevant financial relationships:

 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for:

AbbVie; BiologicsMD; Dermavant; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme; Sun Pharmaceuticals

Serve(d) as a speaker or a member of a speaker’s bureau for: AbbVie; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme

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Alopecia areata (AA) is an autoimmune disease that affects 2% of the population. Janus kinase (JAK) signaling has been shown to improve outcomes for many patients with severe AA, as outlined by Dr Brittany Craiglow, associate professor adjunct, Yale School of Medicine, New Haven, Connecticut.

Dr Craiglow reports that in AA, hair loss can be caused by key cytokines, including interleukin 15 and interferon gamma. These cytokines use the JAK-STAT pathway to transmit their signal. JAK inhibitors, which interfere with that pathway, are showing to be an effective treatment that can lead to hair growth.

Two JAK inhibitors have received US Food and Drug Administration approval for treatment of severe AA. Oral JAK1/2 inhibitor baricitinib has been approved for patients aged 18 years or older. The oral JAK3 inhibitor ritlecitinib has been approved for patients aged 12 years or older.

Dr Craiglow looks at clinical trials involving these JAK inhibitors. The results show that patients are more likely to respond to treatment earlier in the disease process. The study also found that patients with less severe hair loss (50%-94%) respond better than did those with severe hair loss.

Finally, Dr Craiglow explores the topic of JAK inhibitor selection. She notes that different medications will hit different JAK proteins, the failure of one JAK inhibitor does not always predict failure of another. Dr Craiglow points to current efficacy of these targeted therapies and expresses optimism about the future of personalized medicine in treating patients with severe AA.

--

Brittany Craiglow, MD, Associate Professor Adjunct, Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut

Brittany Craiglow, MD, has disclosed the following relevant financial relationships:

 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for:

AbbVie; BiologicsMD; Dermavant; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme; Sun Pharmaceuticals

Serve(d) as a speaker or a member of a speaker’s bureau for: AbbVie; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme

Alopecia areata (AA) is an autoimmune disease that affects 2% of the population. Janus kinase (JAK) signaling has been shown to improve outcomes for many patients with severe AA, as outlined by Dr Brittany Craiglow, associate professor adjunct, Yale School of Medicine, New Haven, Connecticut.

Dr Craiglow reports that in AA, hair loss can be caused by key cytokines, including interleukin 15 and interferon gamma. These cytokines use the JAK-STAT pathway to transmit their signal. JAK inhibitors, which interfere with that pathway, are showing to be an effective treatment that can lead to hair growth.

Two JAK inhibitors have received US Food and Drug Administration approval for treatment of severe AA. Oral JAK1/2 inhibitor baricitinib has been approved for patients aged 18 years or older. The oral JAK3 inhibitor ritlecitinib has been approved for patients aged 12 years or older.

Dr Craiglow looks at clinical trials involving these JAK inhibitors. The results show that patients are more likely to respond to treatment earlier in the disease process. The study also found that patients with less severe hair loss (50%-94%) respond better than did those with severe hair loss.

Finally, Dr Craiglow explores the topic of JAK inhibitor selection. She notes that different medications will hit different JAK proteins, the failure of one JAK inhibitor does not always predict failure of another. Dr Craiglow points to current efficacy of these targeted therapies and expresses optimism about the future of personalized medicine in treating patients with severe AA.

--

Brittany Craiglow, MD, Associate Professor Adjunct, Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut

Brittany Craiglow, MD, has disclosed the following relevant financial relationships:

 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for:

AbbVie; BiologicsMD; Dermavant; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme; Sun Pharmaceuticals

Serve(d) as a speaker or a member of a speaker’s bureau for: AbbVie; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme

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Higher Adherence to the Carbohydrate Quality Index Reduces Migraine Severity and Duration in Women

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Key clinical point: High adherence to the carbohydrate quality index (CQI) was associated with a significant reduction in headache severity and duration in women with migraine.

Major finding: High CQI adherence was associated with low odds of moderate pain (adjusted odds ratio [aOR] 0.37; P = .01), severe pain (aOR 0.22; P = .001), and prolonged headache duration (aOR 0.54; P = .03). Moreover, there was no significant correlation between CQI and migraine disability assessment scores (P > .05).

Study details: This cross-sectional study assessed the association of CQI with headache severity, disability, and duration in 266 women with migraine using a 147-item semiquantitative food frequency questionnaire.

 

Disclosures: The authors did not disclose any source of funding. The authors declared no conflicts of interest.

Source: Jebraeili H, Mirzababaei A, Abaj F, Mirzaei K. The association between carbohydrate quality index and headache severity, disability and duration among women with migraine: A cross-sectional study. Nutr Neurosci. 2024 (May 28). doi: 10.1080/1028415X.2024.2310880 Source

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Key clinical point: High adherence to the carbohydrate quality index (CQI) was associated with a significant reduction in headache severity and duration in women with migraine.

Major finding: High CQI adherence was associated with low odds of moderate pain (adjusted odds ratio [aOR] 0.37; P = .01), severe pain (aOR 0.22; P = .001), and prolonged headache duration (aOR 0.54; P = .03). Moreover, there was no significant correlation between CQI and migraine disability assessment scores (P > .05).

Study details: This cross-sectional study assessed the association of CQI with headache severity, disability, and duration in 266 women with migraine using a 147-item semiquantitative food frequency questionnaire.

 

Disclosures: The authors did not disclose any source of funding. The authors declared no conflicts of interest.

Source: Jebraeili H, Mirzababaei A, Abaj F, Mirzaei K. The association between carbohydrate quality index and headache severity, disability and duration among women with migraine: A cross-sectional study. Nutr Neurosci. 2024 (May 28). doi: 10.1080/1028415X.2024.2310880 Source

Key clinical point: High adherence to the carbohydrate quality index (CQI) was associated with a significant reduction in headache severity and duration in women with migraine.

Major finding: High CQI adherence was associated with low odds of moderate pain (adjusted odds ratio [aOR] 0.37; P = .01), severe pain (aOR 0.22; P = .001), and prolonged headache duration (aOR 0.54; P = .03). Moreover, there was no significant correlation between CQI and migraine disability assessment scores (P > .05).

Study details: This cross-sectional study assessed the association of CQI with headache severity, disability, and duration in 266 women with migraine using a 147-item semiquantitative food frequency questionnaire.

 

Disclosures: The authors did not disclose any source of funding. The authors declared no conflicts of interest.

Source: Jebraeili H, Mirzababaei A, Abaj F, Mirzaei K. The association between carbohydrate quality index and headache severity, disability and duration among women with migraine: A cross-sectional study. Nutr Neurosci. 2024 (May 28). doi: 10.1080/1028415X.2024.2310880 Source

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CGRP mAb Outperform OnabotulinumtoxinA in Difficult-to-Treat Chronic Migraine

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Key clinical point: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were more effective than onabotulinumtoxinA in patients with chronic migraine (CM), even in those who were difficult-to-treat (DTT) and did not respond to ≥3 preventive treatments.

Major finding: At 6 months, CGRP mAb vs onabotulinumtoxinA significantly reduced monthly migraine days (−13.0 vs −8.7 days/month; P < .001) in overall populations, with a similar reduction observed in those who were DTT (−13.0 vs −9.1 days/month; P < .001). Both treatments were well tolerated, with no treatment discontinuation being observed because of adverse events.

Study details: This multicenter, real-world study included 316 and 333 patients with CM who received ≥1 dose of CGRP mAb and onabotulinumtoxinA, respectively, and of whom 544 were DTT and had failed to respond ≥3 preventive treatments.

 

Disclosures: This study was funded by Taiwan National Science and Technology Council and others. Three authors declared receiving research grants, personal fees as advisors or speakers, or honoraria as speakers from various sources.

Source: Wang Y-F, Yang F-C, Chen L-A, et al. Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan. Eur J Neurol. 2024 :e16372 (Jun 5). doi: 10.1111/ene.16372 Source

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Key clinical point: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were more effective than onabotulinumtoxinA in patients with chronic migraine (CM), even in those who were difficult-to-treat (DTT) and did not respond to ≥3 preventive treatments.

Major finding: At 6 months, CGRP mAb vs onabotulinumtoxinA significantly reduced monthly migraine days (−13.0 vs −8.7 days/month; P < .001) in overall populations, with a similar reduction observed in those who were DTT (−13.0 vs −9.1 days/month; P < .001). Both treatments were well tolerated, with no treatment discontinuation being observed because of adverse events.

Study details: This multicenter, real-world study included 316 and 333 patients with CM who received ≥1 dose of CGRP mAb and onabotulinumtoxinA, respectively, and of whom 544 were DTT and had failed to respond ≥3 preventive treatments.

 

Disclosures: This study was funded by Taiwan National Science and Technology Council and others. Three authors declared receiving research grants, personal fees as advisors or speakers, or honoraria as speakers from various sources.

Source: Wang Y-F, Yang F-C, Chen L-A, et al. Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan. Eur J Neurol. 2024 :e16372 (Jun 5). doi: 10.1111/ene.16372 Source

Key clinical point: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were more effective than onabotulinumtoxinA in patients with chronic migraine (CM), even in those who were difficult-to-treat (DTT) and did not respond to ≥3 preventive treatments.

Major finding: At 6 months, CGRP mAb vs onabotulinumtoxinA significantly reduced monthly migraine days (−13.0 vs −8.7 days/month; P < .001) in overall populations, with a similar reduction observed in those who were DTT (−13.0 vs −9.1 days/month; P < .001). Both treatments were well tolerated, with no treatment discontinuation being observed because of adverse events.

Study details: This multicenter, real-world study included 316 and 333 patients with CM who received ≥1 dose of CGRP mAb and onabotulinumtoxinA, respectively, and of whom 544 were DTT and had failed to respond ≥3 preventive treatments.

 

Disclosures: This study was funded by Taiwan National Science and Technology Council and others. Three authors declared receiving research grants, personal fees as advisors or speakers, or honoraria as speakers from various sources.

Source: Wang Y-F, Yang F-C, Chen L-A, et al. Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan. Eur J Neurol. 2024 :e16372 (Jun 5). doi: 10.1111/ene.16372 Source

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Switching Between Anti-CGRP mAb Worsens Disease Burden in Migraine

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Key clinical point: Patients with migraine who switched one or multiple times among available anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments showed lower treatment response and higher disease burden than those who adhered to one anti-CGRP mAb treatment.

Major finding: Overall, 73.1% patients did not switch their anti-CGRP mAb, while 20.6% switched once, 5.4% switched twice, and 0.9% switched three or more times. The ≥50% response rate for monthly migraine days was 64.7% in patients who did not switch among anti-CGRP mAb, but it worsened in those who switched once (50.7%) or twice (25.0%) during their last treatment cycle.

Study details: This real-world retrospective study used data from the Neuro TransData registry and included 655 patients with migraine who received at least one anti-CGRP mAb.

 

Disclosures: The authors did not disclose any source of funding. The authors declared no competing interests.

Source: Hong JB, Israel-Willner H, Peikert A, et al, and the NTD Study Group. Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies — insights from the German NeuroTransData registry. J Headache Pain. 2024;25:90 (Jun 3). doi: 10.1186/s10194-024-01790-7 Source

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Key clinical point: Patients with migraine who switched one or multiple times among available anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments showed lower treatment response and higher disease burden than those who adhered to one anti-CGRP mAb treatment.

Major finding: Overall, 73.1% patients did not switch their anti-CGRP mAb, while 20.6% switched once, 5.4% switched twice, and 0.9% switched three or more times. The ≥50% response rate for monthly migraine days was 64.7% in patients who did not switch among anti-CGRP mAb, but it worsened in those who switched once (50.7%) or twice (25.0%) during their last treatment cycle.

Study details: This real-world retrospective study used data from the Neuro TransData registry and included 655 patients with migraine who received at least one anti-CGRP mAb.

 

Disclosures: The authors did not disclose any source of funding. The authors declared no competing interests.

Source: Hong JB, Israel-Willner H, Peikert A, et al, and the NTD Study Group. Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies — insights from the German NeuroTransData registry. J Headache Pain. 2024;25:90 (Jun 3). doi: 10.1186/s10194-024-01790-7 Source

Key clinical point: Patients with migraine who switched one or multiple times among available anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) treatments showed lower treatment response and higher disease burden than those who adhered to one anti-CGRP mAb treatment.

Major finding: Overall, 73.1% patients did not switch their anti-CGRP mAb, while 20.6% switched once, 5.4% switched twice, and 0.9% switched three or more times. The ≥50% response rate for monthly migraine days was 64.7% in patients who did not switch among anti-CGRP mAb, but it worsened in those who switched once (50.7%) or twice (25.0%) during their last treatment cycle.

Study details: This real-world retrospective study used data from the Neuro TransData registry and included 655 patients with migraine who received at least one anti-CGRP mAb.

 

Disclosures: The authors did not disclose any source of funding. The authors declared no competing interests.

Source: Hong JB, Israel-Willner H, Peikert A, et al, and the NTD Study Group. Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies — insights from the German NeuroTransData registry. J Headache Pain. 2024;25:90 (Jun 3). doi: 10.1186/s10194-024-01790-7 Source

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Meta-Analysis Shows Erenumab Is an Excellent Treatment Option in Migraine

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Key clinical point: A meta-analysis of real-world studies provided strong evidence that erenumab was effective and safe in patients with migraine.

Major finding: At 3 months, erenumab significantly reduced monthly migraine days (mean difference [MD] −7.18 days), monthly headache days (MD 6.89 days), headache impact test-6 scores (MD 6.97), medication days (MD 6.22 days), acute monthly intake (MD 15.75), and pain intensity (MD 1.71), and the results were consistent at 6 and 12 months. The proportion change difference of any adverse event was 0.34 and 0.43 at 6 and 12 months, respectively, with constipation being the most common adverse event (0.19 and 0.20 at 6 and 12 months, respectively).

Study details: Findings are from a meta-analysis of 53 real-world studies including 6509 patients with migraine who were treated with erenumab.

 

Disclosures: This study was funded by the University of Castilla – La Mancha, Spain. The authors declared no conflicts of interest.

Source: Fernández-Bravo-Rodrigo J, Cavero-Redondo I, Lucerón-Lucas-Torres M, et al. Real-world effectiveness and safety of erenumab for the treatment of migraine: A systematic review and meta-analysis. Eur J Pharmacol. 2024;975:176702 (May 31). doi: 10.1016/j.ejphar.2024.17670 Source

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Key clinical point: A meta-analysis of real-world studies provided strong evidence that erenumab was effective and safe in patients with migraine.

Major finding: At 3 months, erenumab significantly reduced monthly migraine days (mean difference [MD] −7.18 days), monthly headache days (MD 6.89 days), headache impact test-6 scores (MD 6.97), medication days (MD 6.22 days), acute monthly intake (MD 15.75), and pain intensity (MD 1.71), and the results were consistent at 6 and 12 months. The proportion change difference of any adverse event was 0.34 and 0.43 at 6 and 12 months, respectively, with constipation being the most common adverse event (0.19 and 0.20 at 6 and 12 months, respectively).

Study details: Findings are from a meta-analysis of 53 real-world studies including 6509 patients with migraine who were treated with erenumab.

 

Disclosures: This study was funded by the University of Castilla – La Mancha, Spain. The authors declared no conflicts of interest.

Source: Fernández-Bravo-Rodrigo J, Cavero-Redondo I, Lucerón-Lucas-Torres M, et al. Real-world effectiveness and safety of erenumab for the treatment of migraine: A systematic review and meta-analysis. Eur J Pharmacol. 2024;975:176702 (May 31). doi: 10.1016/j.ejphar.2024.17670 Source

Key clinical point: A meta-analysis of real-world studies provided strong evidence that erenumab was effective and safe in patients with migraine.

Major finding: At 3 months, erenumab significantly reduced monthly migraine days (mean difference [MD] −7.18 days), monthly headache days (MD 6.89 days), headache impact test-6 scores (MD 6.97), medication days (MD 6.22 days), acute monthly intake (MD 15.75), and pain intensity (MD 1.71), and the results were consistent at 6 and 12 months. The proportion change difference of any adverse event was 0.34 and 0.43 at 6 and 12 months, respectively, with constipation being the most common adverse event (0.19 and 0.20 at 6 and 12 months, respectively).

Study details: Findings are from a meta-analysis of 53 real-world studies including 6509 patients with migraine who were treated with erenumab.

 

Disclosures: This study was funded by the University of Castilla – La Mancha, Spain. The authors declared no conflicts of interest.

Source: Fernández-Bravo-Rodrigo J, Cavero-Redondo I, Lucerón-Lucas-Torres M, et al. Real-world effectiveness and safety of erenumab for the treatment of migraine: A systematic review and meta-analysis. Eur J Pharmacol. 2024;975:176702 (May 31). doi: 10.1016/j.ejphar.2024.17670 Source

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Migraine Not Linked to Atrial Fibrillation Risk

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Key clinical point: Migraine, migraine with aura (MA), and migraine without aura (MO) were not associated with a higher risk for atrial fibrillation (AF), with migraine and its subtypes serving as a protective factor for AF in individuals age ≥ 55 years with migraine.

Major finding: No significant association was found between migraine (adjusted hazard ratio [aHR] 0.76; 95% CI 0.48-1.18), MA (aHR 1.00; 95% CI 0.59-1.70), or MO (aHR 0.50; 95% CI 0.23-1.06) and the risk for AF. However, among patients age ≥ 55 years, the risk for AF was significantly lower in those with migraine (aHR 0.53; 95% CI 0.39-0.73), MA (aHR 0.58; 95% CI 0.38-0.87), or MO (aHR 0.48; 95% CI 0.30-0.78) than in those without headache.

Study details: This prospective, population-based 9-year follow-up study included 39,340 individuals (age 20 years) without AF who answered the headache questionnaire during the Trøndelag Health Study; of these, 1524 (3.8%) developed AF.

 

Disclosures: This study did not receive any specific funding from any sources. The authors declared no conflicts of interest.

Source: Giri S, Tronvik E, Dalen H, et al. Migraine and risk of atrial fibrillation: A 9-year follow-up based on the Trøndelag Health Study. Cephalalgia. 2024 (May 29). doi: 10.1177/03331024241254517 Source

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Key clinical point: Migraine, migraine with aura (MA), and migraine without aura (MO) were not associated with a higher risk for atrial fibrillation (AF), with migraine and its subtypes serving as a protective factor for AF in individuals age ≥ 55 years with migraine.

Major finding: No significant association was found between migraine (adjusted hazard ratio [aHR] 0.76; 95% CI 0.48-1.18), MA (aHR 1.00; 95% CI 0.59-1.70), or MO (aHR 0.50; 95% CI 0.23-1.06) and the risk for AF. However, among patients age ≥ 55 years, the risk for AF was significantly lower in those with migraine (aHR 0.53; 95% CI 0.39-0.73), MA (aHR 0.58; 95% CI 0.38-0.87), or MO (aHR 0.48; 95% CI 0.30-0.78) than in those without headache.

Study details: This prospective, population-based 9-year follow-up study included 39,340 individuals (age 20 years) without AF who answered the headache questionnaire during the Trøndelag Health Study; of these, 1524 (3.8%) developed AF.

 

Disclosures: This study did not receive any specific funding from any sources. The authors declared no conflicts of interest.

Source: Giri S, Tronvik E, Dalen H, et al. Migraine and risk of atrial fibrillation: A 9-year follow-up based on the Trøndelag Health Study. Cephalalgia. 2024 (May 29). doi: 10.1177/03331024241254517 Source

Key clinical point: Migraine, migraine with aura (MA), and migraine without aura (MO) were not associated with a higher risk for atrial fibrillation (AF), with migraine and its subtypes serving as a protective factor for AF in individuals age ≥ 55 years with migraine.

Major finding: No significant association was found between migraine (adjusted hazard ratio [aHR] 0.76; 95% CI 0.48-1.18), MA (aHR 1.00; 95% CI 0.59-1.70), or MO (aHR 0.50; 95% CI 0.23-1.06) and the risk for AF. However, among patients age ≥ 55 years, the risk for AF was significantly lower in those with migraine (aHR 0.53; 95% CI 0.39-0.73), MA (aHR 0.58; 95% CI 0.38-0.87), or MO (aHR 0.48; 95% CI 0.30-0.78) than in those without headache.

Study details: This prospective, population-based 9-year follow-up study included 39,340 individuals (age 20 years) without AF who answered the headache questionnaire during the Trøndelag Health Study; of these, 1524 (3.8%) developed AF.

 

Disclosures: This study did not receive any specific funding from any sources. The authors declared no conflicts of interest.

Source: Giri S, Tronvik E, Dalen H, et al. Migraine and risk of atrial fibrillation: A 9-year follow-up based on the Trøndelag Health Study. Cephalalgia. 2024 (May 29). doi: 10.1177/03331024241254517 Source

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Predictors for Anti-CGRP mAb Response in Migraine

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Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were well tolerated and effective in treating high-frequency episodic or chronic migraine, with factors such as unilateral pain, fewer migraine days, and lower disability associated with good and excellent responses to anti-CGRP mAb treatment.

Major finding: At 6 months, 56.5% and 26.7% patients receiving anti-CGRP mAb showed good and excellent responses (≥50% vs ≥75% reduction in monthly headache days), respectively. The presence of unilateral pain, fewer monthly migraine days, and a low Migraine Disability Assessment Score were independent predictors of good (area under the curve [AUC] 0.648; 95% CI 0.616-0.680) and excellent (AUC 0.691; 95% CI 0.651-0.731) responses to anti-CGRP mAb treatment.

Study details: This prospective multicenter real-world study included 4963 patients with high-frequency episodic or chronic migraine who received anti-CGRP mAb treatment with a 6-month follow-up.

Disclosures: This study did not receive specific funding from any sources. Several authors declared receiving speaker honoraria, travel grants, or honoraria from or having other ties with various sources.

Source: Caronna E, Gallardo VJ, Egeo G, et al, for the EUREkA study group. Redefining migraine prevention: Early treatment with anti-CGRP monoclonal antibodies enhances response in the real world. J Neurol Neurosurg Psychiatry. 2024 (May 22). doi: 10.1136/jnnp-2023-333295 Source

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Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were well tolerated and effective in treating high-frequency episodic or chronic migraine, with factors such as unilateral pain, fewer migraine days, and lower disability associated with good and excellent responses to anti-CGRP mAb treatment.

Major finding: At 6 months, 56.5% and 26.7% patients receiving anti-CGRP mAb showed good and excellent responses (≥50% vs ≥75% reduction in monthly headache days), respectively. The presence of unilateral pain, fewer monthly migraine days, and a low Migraine Disability Assessment Score were independent predictors of good (area under the curve [AUC] 0.648; 95% CI 0.616-0.680) and excellent (AUC 0.691; 95% CI 0.651-0.731) responses to anti-CGRP mAb treatment.

Study details: This prospective multicenter real-world study included 4963 patients with high-frequency episodic or chronic migraine who received anti-CGRP mAb treatment with a 6-month follow-up.

Disclosures: This study did not receive specific funding from any sources. Several authors declared receiving speaker honoraria, travel grants, or honoraria from or having other ties with various sources.

Source: Caronna E, Gallardo VJ, Egeo G, et al, for the EUREkA study group. Redefining migraine prevention: Early treatment with anti-CGRP monoclonal antibodies enhances response in the real world. J Neurol Neurosurg Psychiatry. 2024 (May 22). doi: 10.1136/jnnp-2023-333295 Source

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) were well tolerated and effective in treating high-frequency episodic or chronic migraine, with factors such as unilateral pain, fewer migraine days, and lower disability associated with good and excellent responses to anti-CGRP mAb treatment.

Major finding: At 6 months, 56.5% and 26.7% patients receiving anti-CGRP mAb showed good and excellent responses (≥50% vs ≥75% reduction in monthly headache days), respectively. The presence of unilateral pain, fewer monthly migraine days, and a low Migraine Disability Assessment Score were independent predictors of good (area under the curve [AUC] 0.648; 95% CI 0.616-0.680) and excellent (AUC 0.691; 95% CI 0.651-0.731) responses to anti-CGRP mAb treatment.

Study details: This prospective multicenter real-world study included 4963 patients with high-frequency episodic or chronic migraine who received anti-CGRP mAb treatment with a 6-month follow-up.

Disclosures: This study did not receive specific funding from any sources. Several authors declared receiving speaker honoraria, travel grants, or honoraria from or having other ties with various sources.

Source: Caronna E, Gallardo VJ, Egeo G, et al, for the EUREkA study group. Redefining migraine prevention: Early treatment with anti-CGRP monoclonal antibodies enhances response in the real world. J Neurol Neurosurg Psychiatry. 2024 (May 22). doi: 10.1136/jnnp-2023-333295 Source

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