Photoallergic Contact Dermatitis: No Fun in the Sun

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Photoallergic Contact Dermatitis: No Fun in the Sun

Photoallergic contact dermatitis (PACD), a subtype of allergic contact dermatitis that occurs because of the specific combination of exposure to an exogenous chemical applied topically to the skin and UV radiation, may be more common than was once thought.1 Although the incidence in the general population is unknown, current research points to approximately 20% to 40% of patients with suspected photosensitivity having a PACD diagnosis.2 Recently, the North American Contact Dermatitis Group (NACDG) reported that 21% of 373 patients undergoing photopatch testing (PPT) were diagnosed with PACD2; however, PPT is not routinely performed, which may contribute to underdiagnosis.

Mechanism of Disease

Similar to allergic contact dermatitis, PACD is a delayed type IV hypersensitivity reaction; however, it only occurs when an exogenous chemical is applied topically to the skin with concomitant exposure to UV radiation, usually in the UVA range (315–400 nm).3,4 When exposed to UV radiation, it is thought that the exogenous chemical combines with a protein in the skin and transforms into a photoantigen. In the sensitization phase, the photoantigen is taken up by antigen-presenting cells in the epidermis and transported to local lymph nodes where antigen-specific T cells are generated.5 In the elicitation phase, the inflammatory reaction of PACD occurs upon subsequent exposure to the same chemical plus UV radiation.4 Development of PACD does not necessarily depend on the dose of the chemical or the amount of UV radiation.6 Why certain individuals may be more susceptible is unknown, though major histocompatibility complex haplotypes could be influential.7,8

Clinical Manifestations

Photoallergic contact dermatitis primarily presents in sun-exposed areas of the skin (eg, face, neck, V area of the chest, dorsal upper extremities) with sparing of naturally photoprotected sites, such as the upper eyelids and nasolabial and retroauricular folds. Other than its characteristic photodistribution, PACD often is clinically indistinguishable from routine allergic contact dermatitis. It manifests as a pruritic, poorly demarcated, eczematous or sometimes vesiculobullous eruption that develops in a delayed fashion—24 to 72 hours after sun exposure. The dermatitis may extend to other parts of the body either through spread of the chemical agent by the hands or clothing or due to the systemic nature of the immune response. The severity of the presentation can vary depending on multiple factors, such as concentration and absorption of the agent, length of exposure, intensity and duration of UV radiation exposure, and individual susceptibility.4 Chronic PACD may become lichenified. Generally, rashes resolve after discontinuation of the causative agent; however, long-term exposure may lead to development of chronic actinic dermatitis, with persistent photodistributed eczema regardless of contact with the initial inciting agent.9

Differential Diagnosis

The differential diagnosis for patients presenting with photodistributed dermatitis is broad; therefore, taking a thorough history is important. Considerations include age of onset, timing and persistence of reactions, use of topical and systemic medications (both prescription and over-the-counter [OTC]), personal care products, occupation, and hobbies, as well as a thorough review of systems.

It is important to distinguish PACD from phototoxic contact dermatitis (PTCD)(also known as photoirritant contact dermatitis)(Table). Asking about the onset and timing of the eruption may be critical for distinction, as PTCD can occur within minutes to hours of the first exposure to a chemical and UV radiation, while there is a sensitization delay in PACD.6 Phytophotodermatitis is a well-known type of PTCD caused by exposure to furocoumarin-containing plants, most commonly limes.10 Other causes of PTCD include tar products and certain medications.11 Importantly, PPT to a known phototoxic chemical should never be performed because it will cause a strong reaction in anyone tested, regardless of exposure history.

Comparison of Phototoxic and Photoallergic Contact Dermatitis


Other diagnoses to consider include photoaggravated dermatoses (eg, atopic dermatitis, lupus erythematosus, dermatomyositis) and idiopathic photodermatoses (eg, chronic actinic dermatitis, actinic prurigo, polymorphous light eruption). Although atopic dermatitis usually improves with UV light exposure, photoaggravated atopic dermatitis is suggested in eczema patients who flare with sun exposure, in a seasonal pattern, or after phototherapy; this condition is challenging to differentiate from PACD if PPT is not performed.12 The diagnosis of idiopathic photodermatoses is nuanced; however, asking about the timeline of the reaction including onset, duration, and persistence, as well as characterization of unique clinical features, can help in differentiation.13 In certain scenarios, a biopsy may be helpful. A thorough review of systems will help to assess for autoimmune connective tissue disorders, and relevant serologies should be checked as indicated.

Diagnosis

Histologically, PACD presents similarly to allergic contact dermatitis with spongiotic dermatitis; therefore, biopsy cannot be relied upon to make the diagnosis.6 Photopatch testing is required for definitive diagnosis. It is reasonable to perform PPT in any patient with chronic dermatitis primarily affecting sun-exposed areas without a clear alternative diagnosis.14,15 Of note, at present there are no North American consensus guidelines for PPT, but typically duplicate sets of photoallergens are applied to both sides of the patient’s back and one side is exposed to UVA radiation. The reactions are compared after 48 to 96 hours.15 A positive reaction only at the irradiated site is consistent with photoallergy, while a reaction of equal strength at both the irradiated and nonirradiated sites indicates regular contact allergy. The case of a reaction occurring at both sites with a stronger response at the irradiated site is known as photoaggravated contact allergy, which can be thought of as allergic contact dermatitis that worsens but does not solely occur with exposure to sunlight.

 

 

Although PPT is necessary for the accurate diagnosis of PACD, it is infrequently used. Two surveys of 112 and 117 American Contact Dermatitis Society members, respectively, have revealed that only around half performed PPT, most of them testing fewer than 20 times per year.16,17 Additionally, there was variability in the test methodology and allergens employed. Nevertheless, most respondents tested sunscreens, nonsteroidal anti-inflammatory drugs (NSAIDs), fragrances, and their patients’ own products.16,17 The most common reasons for not performing PPT were lack of equipment, insufficient skills, rare clinical suspicion, and cost. Dermatologists at academic centers performed more PPT than those in other practice settings, including multispecialty group practices and private offices.16 These findings highlight multiple factors that may contribute to reduced patient access to PPT and thus potential underdiagnosis of PACD.

Common Photoallergens

The most common photoallergens change over time in response to market trends; for example, fragrance was once a top photoallergen in the United States in the 1970s and 1980s but declined in prominence after musk ambrette—the primary allergen associated with PACD at the time—was removed as an ingredient in fragrances.18

In the largest and most recent PPT series from North America (1999-2009),2 sunscreens comprised 7 of the top 10 most common photoallergens, which is consistent with other studies showing sunscreens to be the most common North American photoallergens.19-22 The frequency of PACD due to sunscreens likely relates to their increasing use worldwide as awareness of photocarcinogenesis and photoaging grows, as well as the common use of UV filters in nonsunscreen personal care products, ranging from lip balms to perfumes and bodywashes. Chemical (organic) UV filters—in particular oxybenzone (benzophenone-3) and avobenzone (butyl methoxydibenzoylmethane)—are the most common sunscreen photoallergens.2,23 Para-aminobenzoic acid was once a common photoallergen, but it is no longer used in US sunscreens due to safety concerns.19,20 The physical (inorganic) UV filters zinc oxide and titanium dioxide are not known photosensitizers.

Methylisothiazolinone (MI) is a highly allergenic preservative commonly used in a wide array of personal care products, including sunscreens.24 In the most recent NACDG patch test data, MI was the second most common contact allergen.25 Allergic contact dermatitis caused by MI in sunscreen can mimic PACD.26 In addition, MI can cause photoaggravated contact dermatitis, with some affected patients experiencing ongoing photosensitivity even after avoiding this allergen.26-30 The European Union and Canada have introduced restrictions on the use of MI in personal care products, but no such regulatory measures have been taken in the United States to date.25,31,32

After sunscreens, another common cause of PACD are topical NSAIDs, which are frequently used for musculoskeletal pain relief. These are of particular concern in Europe, where a variety of formulations are widely available OTC.33 Ketoprofen and etofenamate are responsible for the largest number of PACD reactions in Europe.2,34,35 Meanwhile, the only OTC topical NSAID available in the United States is diclofenac gel, which was approved in 2020. Cases of PACD due to use of diclofenac gel have been reported in the literature, but testing in larger populations is needed.36-39

Notably, ketoprofen may co- or cross-react with certain UV filters—oxybenzone and octocrylene—and the lipid-lowering agent fenofibrate due to chemical similarities.40-43 Despite the relatively high number of photoallergic reactions to ketoprofen in the NACDG photopatch series, only 25% (5/20) were considered clinically relevant (ie, the allergen could not be verified as present in the known skin contactants of the patient, and the patient was not exposed to circumstances in which contact with materials known to contain the allergen would likely occur), which suggests that they likely represented cross-reactions in patients sensitized to sunscreens.2

Other agents that may cause PACD include antimicrobials, plants and plant derivatives, and pesticides.2,4,18 The antimicrobial fentichlor is a common cause of positive PPT reactions, but it rarely is clinically relevant.44

Treatment

The primary management of PACD centers on identification of the causative photoallergen to avoid future exposure. Patients should be educated on the various names by which the causative allergen can be identified on product labels and should be given a list of safe products that are free from relevant allergens and cross-reacting chemicals.45 Additionally, sun protection education should be provided. Exposure to UVA radiation can occur through windows, making the use of broad-spectrum sunscreens and protective clothing crucial. In cases of sunscreen-induced PACD, the responsible chemical UV filter(s) should be avoided, or alternatively, patients may use physical sunscreens containing only zinc oxide and/or titanium dioxide as active ingredients, as these are not known to cause PACD.4

When avoidance alone is insufficient, topical corticosteroids are the usual first-line treatment for localized PACD. When steroid-sparing treatments are preferred, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used. If PACD is more widespread and severe, systemic therapy using steroids or steroid-sparing agents may be necessary to provide symptomatic relief.4

Final Interpretation

Photoallergic contact dermatitis is not uncommon, particularly among photosensitive patients. Most cases are due to sunscreens or topical NSAIDs. Consideration of PPT should be given in any patient with a chronic photodistributed dermatitis to evaluate for the possibility of PACD.

References
  1. Darvay A, White IR, Rycroft RJ, et al. Photoallergic contact dermatitis is uncommon. Br J Dermatol. 2001;145:597-601.
  2. DeLeo VA, Adler BL, Warshaw EM, et al. Photopatch test results of the North American contact dermatitis group, 1999-2009. Photodermatol Photoimmunol Photomed. 2022;38:288-291.
  3. Kerr A, Ferguson J. Photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed. 2010;26:56-65.
  4. As¸kın Ö, Cesur SK, Engin B, et al. Photoallergic contact dermatitis. Curr Derm Rep. 2019;8:157-163.
  5. Wilm A, Berneburg M. Photoallergy. J Dtsch Dermatol Ges. 2015;13:7-13.
  6. DeLeo VA. Photocontact dermatitis. Dermatol Ther. 2004;17:279-288. 
  7. Imai S, Atarashi K, Ikesue K, et al. Establishment of murine model of allergic photocontact dermatitis to ketoprofen and characterization of pathogenic T cells. J Dermatol Sci. 2006;41:127-136.
  8. Tokura Y, Yagi H, Satoh T, et al. Inhibitory effect of melanin pigment on sensitization and elicitation of murine contact photosensitivity: mechanism of low responsiveness in C57BL/10 background mice. J Invest Dermatol. 1993;101:673-678.
  9. Stein KR, Scheinfeld NS. Drug-induced photoallergic and phototoxic reactions. Expert Opin Drug Saf. 2007;6:431-443.
  10. Janusz SC, Schwartz RA. Botanical briefs: phytophotodermatitis is an occupational and recreational dermatosis in the limelight. Cutis. 2021;107:187-189.
  11. Atwal SK, Chen A, Adler BL. Phototoxic contact dermatitis from over-the-counter 8-methoxypsoralen. Cutis. 2022;109:E2-E3.
  12. Rutter KJ, Farrar MD, Marjanovic EJ, et al. Clinicophotobiological characterization of photoaggravated atopic dermatitis [published online July 27, 2022]. JAMA Dermatol. doi:10.1001/jamadermatol.2022.2823
  13. Lecha M. Idiopathic photodermatoses: clinical, diagnostic and therapeutic aspects. J Eur Acad Dermatol Venereol. 2001;15:499-505.
  14. Marks JG Jr, Anderson BE, DeLeo VA. Contact & Occupational Dermatology. 4th ed. Jaypee Brothers; 2016.
  15. Bruynzeel DP, Ferguson J, Andersen K, et al. Photopatch testing: a consensus methodology for Europe. J Eur Acad Dermatol Venereol. 2004;18:679-682. 
  16. Kim T, Taylor JS, Maibach HI, et al. Photopatch testing among members of the American Contact Dermatitis Society. Dermatitis. 2020;31:59-67.
  17. Asemota E, Crawford G, Kovarik C, et al. A survey examining photopatch test and phototest methodologies of contact dermatologists in the United States: platform for developing a consensus. Dermatitis. 2017;28:265-269.
  18. Scalf LA, Davis MD, Rohlinger AL, et al. Photopatch testing of 182 patients: a 6-year experience at the Mayo Clinic. Dermatitis. 2009;20:44-52.
  19. Greenspoon J, Ahluwalia R, Juma N, et al. Allergic and photoallergic contact dermatitis: a 10-year experience. Dermatitis. 2013;24:29-32.
  20. Victor FC, Cohen DE, Soter NA. A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis. J Am Acad Dermatol. 2010;62:605-610.
  21. Schauder S, Ippen H. Contact and photocontact sensitivity to sunscreens. review of a 15-year experience and of the literature. Contact Dermatitis. 1997;37:221-232. 
  22. Collaris EJ, Frank J. Photoallergic contact dermatitis caused by ultraviolet filters in different sunscreens. Int J Dermatol. 2008;47(suppl 1):35-37.
  23. Heurung AR, Raju SI, Warshaw EM. Adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management. Dermatitis. 2014;25:289-326.
  24. Reeder M, Atwater AR. Methylisothiazolinone and isothiazolinone allergy. Cutis. 2019;104:94-96.
  25. DeKoven JG, Silverberg JI, Warshaw EM, et al. North American Contact Dermatitis Group Patch Test Results: 2017-2018. Dermatitis. 2021;32:111-123.
  26. Kullberg SA, Voller LM, Warshaw EM. Methylisothiazolinone in “dermatology-recommended” sunscreens: an important mimicker of photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed. 2021;37:366-370. 
  27. Herman A, Aerts O, de Montjoye L, et al. Isothiazolinone derivatives and allergic contact dermatitis: a review and update. J Eur Acad Dermatol Venereol. 2019;33:267-276.
  28. Adler BL, Houle MC, Pratt M. Photoaggravated contact dermatitis to methylisothiazolinone and associated photosensitivity: a case series [published online January 25, 2022]. Dermatitis. doi:10.1097/DER.0000000000000833
  29. Aerts O, Goossens A, Marguery MC, et al. Photoaggravated allergic contact dermatitis and transient photosensitivity caused by methylisothiazolinone. Contact Dermatitis. 2018;78:241-245.
  30. Pirmez R, Fernandes AL, Melo MG. Photoaggravated contact dermatitis to Kathon CG (methylchloroisothiazolinone/methylisothiazolinone): a novel pattern of involvement in a growing epidemic?. Br J Dermatol. 2015;173:1343-1344.
  31. Uter W, Aalto-Korte K, Agner T, et al. The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.J Eur Acad Dermatol Venereol. 2020;34:333-339.
  32. Government of Canada. Changes to the cosmetic ingredient hotlist. December 3, 2019. Updated August 26, 2022. Accessed October 20, 2022. https://www.canada.ca/en/health-canada/services/consumer-product-safety/cosmetics/cosmetic-ingredient-hotlist-prohibited-restricted-ingredients/changes.html
  33. Barkin RL. Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther. 2015;22:388-407.
  34. European Multicentre Photopatch Test Study (EMCPPTS) Taskforce. A European multicentre photopatch test study. Br J Dermatol. 2012;166:1002-1009.
  35. Ophaswongse S, Maibach H. Topical nonsteroidal antiinflammatory drugs: allergic and photoallergic contact dermatitis and phototoxicity. Contact Dermatitis. 1993;29:57-64. 
  36. Kowalzick L, Ziegler H. Photoallergic contact dermatitis from topical diclofenac in Solaraze gel. Contact Dermatitis. 2006;54:348-349.
  37. Montoro J, Rodríguez M, Díaz M, et al. Photoallergic contact dermatitis due to diclofenac. Contact Dermatitis. 2003;48:115.
  38. Fernández-Jorge B, Goday-Buján JJ, Murga M, et al. Photoallergic contact dermatitis due to diclofenac with cross-reaction to aceclofenac: two case reports. Contact Dermatitis. 2009;61:236-237.
  39. Akat PB. Severe photosensitivity reaction induced by topical diclofenac. Indian J Pharmacol. 2013;45:408-409.
  40. Leroy D, Dompmartin A, Szczurko C, et al. Photodermatitis from ketoprofen with cross-reactivity to fenofibrate and benzophenones. Photodermatol Photoimmunol Photomed. 1997;13:93-97.
  41. Devleeschouwer V, Roelandts R, Garmyn M, et al. Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients. Contact Dermatitis. 2008;58:159-166.
  42. Matsushita T, Kamide R. Five cases of photocontact dermatitisdue to topical ketoprofen: photopatch testing and cross-reaction study. Photodermatol Photoimmunol Photomed. 2001;17:26-31.
  43. de Groot AC, Roberts DW. Contact and photocontact allergy to octocrylene: a review. Contact Dermatitis. 2014;70:193-204.
  44. Wolverton JE, Soter NA, Cohen DE. Fentichlor photocontact dermatitis: a persistent enigma. Dermatitis. 2013;24:77-81.
  45. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient management and education. J Am Acad Dermatol. 2016;74:1043-1054.
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Ms. Guenther and Dr. Adler are from the Keck School of Medicine, University of Southern California, Los Angeles. Dr. Adler is from the Department of Dermatology. Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.

Ms. Guenther and Ms. Johnson report no conflict of interest. Dr. Yu has served as a speaker for the National Eczema Foundation, has received research grants from the Dermatology Foundation and the Pediatric Dermatology Foundation, and has received income from Dynamed. Dr. Adler has served as a research investigator and/or consultant to AbbVie and Skin Research Institute, LLC.

Correspondence: Brandon L. Adler, MD, 1441 Eastlake Ave, Ezralow Tower, Ste 5301, Los Angeles, CA 90033 ([email protected]).

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Ms. Guenther and Dr. Adler are from the Keck School of Medicine, University of Southern California, Los Angeles. Dr. Adler is from the Department of Dermatology. Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.

Ms. Guenther and Ms. Johnson report no conflict of interest. Dr. Yu has served as a speaker for the National Eczema Foundation, has received research grants from the Dermatology Foundation and the Pediatric Dermatology Foundation, and has received income from Dynamed. Dr. Adler has served as a research investigator and/or consultant to AbbVie and Skin Research Institute, LLC.

Correspondence: Brandon L. Adler, MD, 1441 Eastlake Ave, Ezralow Tower, Ste 5301, Los Angeles, CA 90033 ([email protected]).

Author and Disclosure Information

Ms. Guenther and Dr. Adler are from the Keck School of Medicine, University of Southern California, Los Angeles. Dr. Adler is from the Department of Dermatology. Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.

Ms. Guenther and Ms. Johnson report no conflict of interest. Dr. Yu has served as a speaker for the National Eczema Foundation, has received research grants from the Dermatology Foundation and the Pediatric Dermatology Foundation, and has received income from Dynamed. Dr. Adler has served as a research investigator and/or consultant to AbbVie and Skin Research Institute, LLC.

Correspondence: Brandon L. Adler, MD, 1441 Eastlake Ave, Ezralow Tower, Ste 5301, Los Angeles, CA 90033 ([email protected]).

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Photoallergic contact dermatitis (PACD), a subtype of allergic contact dermatitis that occurs because of the specific combination of exposure to an exogenous chemical applied topically to the skin and UV radiation, may be more common than was once thought.1 Although the incidence in the general population is unknown, current research points to approximately 20% to 40% of patients with suspected photosensitivity having a PACD diagnosis.2 Recently, the North American Contact Dermatitis Group (NACDG) reported that 21% of 373 patients undergoing photopatch testing (PPT) were diagnosed with PACD2; however, PPT is not routinely performed, which may contribute to underdiagnosis.

Mechanism of Disease

Similar to allergic contact dermatitis, PACD is a delayed type IV hypersensitivity reaction; however, it only occurs when an exogenous chemical is applied topically to the skin with concomitant exposure to UV radiation, usually in the UVA range (315–400 nm).3,4 When exposed to UV radiation, it is thought that the exogenous chemical combines with a protein in the skin and transforms into a photoantigen. In the sensitization phase, the photoantigen is taken up by antigen-presenting cells in the epidermis and transported to local lymph nodes where antigen-specific T cells are generated.5 In the elicitation phase, the inflammatory reaction of PACD occurs upon subsequent exposure to the same chemical plus UV radiation.4 Development of PACD does not necessarily depend on the dose of the chemical or the amount of UV radiation.6 Why certain individuals may be more susceptible is unknown, though major histocompatibility complex haplotypes could be influential.7,8

Clinical Manifestations

Photoallergic contact dermatitis primarily presents in sun-exposed areas of the skin (eg, face, neck, V area of the chest, dorsal upper extremities) with sparing of naturally photoprotected sites, such as the upper eyelids and nasolabial and retroauricular folds. Other than its characteristic photodistribution, PACD often is clinically indistinguishable from routine allergic contact dermatitis. It manifests as a pruritic, poorly demarcated, eczematous or sometimes vesiculobullous eruption that develops in a delayed fashion—24 to 72 hours after sun exposure. The dermatitis may extend to other parts of the body either through spread of the chemical agent by the hands or clothing or due to the systemic nature of the immune response. The severity of the presentation can vary depending on multiple factors, such as concentration and absorption of the agent, length of exposure, intensity and duration of UV radiation exposure, and individual susceptibility.4 Chronic PACD may become lichenified. Generally, rashes resolve after discontinuation of the causative agent; however, long-term exposure may lead to development of chronic actinic dermatitis, with persistent photodistributed eczema regardless of contact with the initial inciting agent.9

Differential Diagnosis

The differential diagnosis for patients presenting with photodistributed dermatitis is broad; therefore, taking a thorough history is important. Considerations include age of onset, timing and persistence of reactions, use of topical and systemic medications (both prescription and over-the-counter [OTC]), personal care products, occupation, and hobbies, as well as a thorough review of systems.

It is important to distinguish PACD from phototoxic contact dermatitis (PTCD)(also known as photoirritant contact dermatitis)(Table). Asking about the onset and timing of the eruption may be critical for distinction, as PTCD can occur within minutes to hours of the first exposure to a chemical and UV radiation, while there is a sensitization delay in PACD.6 Phytophotodermatitis is a well-known type of PTCD caused by exposure to furocoumarin-containing plants, most commonly limes.10 Other causes of PTCD include tar products and certain medications.11 Importantly, PPT to a known phototoxic chemical should never be performed because it will cause a strong reaction in anyone tested, regardless of exposure history.

Comparison of Phototoxic and Photoallergic Contact Dermatitis


Other diagnoses to consider include photoaggravated dermatoses (eg, atopic dermatitis, lupus erythematosus, dermatomyositis) and idiopathic photodermatoses (eg, chronic actinic dermatitis, actinic prurigo, polymorphous light eruption). Although atopic dermatitis usually improves with UV light exposure, photoaggravated atopic dermatitis is suggested in eczema patients who flare with sun exposure, in a seasonal pattern, or after phototherapy; this condition is challenging to differentiate from PACD if PPT is not performed.12 The diagnosis of idiopathic photodermatoses is nuanced; however, asking about the timeline of the reaction including onset, duration, and persistence, as well as characterization of unique clinical features, can help in differentiation.13 In certain scenarios, a biopsy may be helpful. A thorough review of systems will help to assess for autoimmune connective tissue disorders, and relevant serologies should be checked as indicated.

Diagnosis

Histologically, PACD presents similarly to allergic contact dermatitis with spongiotic dermatitis; therefore, biopsy cannot be relied upon to make the diagnosis.6 Photopatch testing is required for definitive diagnosis. It is reasonable to perform PPT in any patient with chronic dermatitis primarily affecting sun-exposed areas without a clear alternative diagnosis.14,15 Of note, at present there are no North American consensus guidelines for PPT, but typically duplicate sets of photoallergens are applied to both sides of the patient’s back and one side is exposed to UVA radiation. The reactions are compared after 48 to 96 hours.15 A positive reaction only at the irradiated site is consistent with photoallergy, while a reaction of equal strength at both the irradiated and nonirradiated sites indicates regular contact allergy. The case of a reaction occurring at both sites with a stronger response at the irradiated site is known as photoaggravated contact allergy, which can be thought of as allergic contact dermatitis that worsens but does not solely occur with exposure to sunlight.

 

 

Although PPT is necessary for the accurate diagnosis of PACD, it is infrequently used. Two surveys of 112 and 117 American Contact Dermatitis Society members, respectively, have revealed that only around half performed PPT, most of them testing fewer than 20 times per year.16,17 Additionally, there was variability in the test methodology and allergens employed. Nevertheless, most respondents tested sunscreens, nonsteroidal anti-inflammatory drugs (NSAIDs), fragrances, and their patients’ own products.16,17 The most common reasons for not performing PPT were lack of equipment, insufficient skills, rare clinical suspicion, and cost. Dermatologists at academic centers performed more PPT than those in other practice settings, including multispecialty group practices and private offices.16 These findings highlight multiple factors that may contribute to reduced patient access to PPT and thus potential underdiagnosis of PACD.

Common Photoallergens

The most common photoallergens change over time in response to market trends; for example, fragrance was once a top photoallergen in the United States in the 1970s and 1980s but declined in prominence after musk ambrette—the primary allergen associated with PACD at the time—was removed as an ingredient in fragrances.18

In the largest and most recent PPT series from North America (1999-2009),2 sunscreens comprised 7 of the top 10 most common photoallergens, which is consistent with other studies showing sunscreens to be the most common North American photoallergens.19-22 The frequency of PACD due to sunscreens likely relates to their increasing use worldwide as awareness of photocarcinogenesis and photoaging grows, as well as the common use of UV filters in nonsunscreen personal care products, ranging from lip balms to perfumes and bodywashes. Chemical (organic) UV filters—in particular oxybenzone (benzophenone-3) and avobenzone (butyl methoxydibenzoylmethane)—are the most common sunscreen photoallergens.2,23 Para-aminobenzoic acid was once a common photoallergen, but it is no longer used in US sunscreens due to safety concerns.19,20 The physical (inorganic) UV filters zinc oxide and titanium dioxide are not known photosensitizers.

Methylisothiazolinone (MI) is a highly allergenic preservative commonly used in a wide array of personal care products, including sunscreens.24 In the most recent NACDG patch test data, MI was the second most common contact allergen.25 Allergic contact dermatitis caused by MI in sunscreen can mimic PACD.26 In addition, MI can cause photoaggravated contact dermatitis, with some affected patients experiencing ongoing photosensitivity even after avoiding this allergen.26-30 The European Union and Canada have introduced restrictions on the use of MI in personal care products, but no such regulatory measures have been taken in the United States to date.25,31,32

After sunscreens, another common cause of PACD are topical NSAIDs, which are frequently used for musculoskeletal pain relief. These are of particular concern in Europe, where a variety of formulations are widely available OTC.33 Ketoprofen and etofenamate are responsible for the largest number of PACD reactions in Europe.2,34,35 Meanwhile, the only OTC topical NSAID available in the United States is diclofenac gel, which was approved in 2020. Cases of PACD due to use of diclofenac gel have been reported in the literature, but testing in larger populations is needed.36-39

Notably, ketoprofen may co- or cross-react with certain UV filters—oxybenzone and octocrylene—and the lipid-lowering agent fenofibrate due to chemical similarities.40-43 Despite the relatively high number of photoallergic reactions to ketoprofen in the NACDG photopatch series, only 25% (5/20) were considered clinically relevant (ie, the allergen could not be verified as present in the known skin contactants of the patient, and the patient was not exposed to circumstances in which contact with materials known to contain the allergen would likely occur), which suggests that they likely represented cross-reactions in patients sensitized to sunscreens.2

Other agents that may cause PACD include antimicrobials, plants and plant derivatives, and pesticides.2,4,18 The antimicrobial fentichlor is a common cause of positive PPT reactions, but it rarely is clinically relevant.44

Treatment

The primary management of PACD centers on identification of the causative photoallergen to avoid future exposure. Patients should be educated on the various names by which the causative allergen can be identified on product labels and should be given a list of safe products that are free from relevant allergens and cross-reacting chemicals.45 Additionally, sun protection education should be provided. Exposure to UVA radiation can occur through windows, making the use of broad-spectrum sunscreens and protective clothing crucial. In cases of sunscreen-induced PACD, the responsible chemical UV filter(s) should be avoided, or alternatively, patients may use physical sunscreens containing only zinc oxide and/or titanium dioxide as active ingredients, as these are not known to cause PACD.4

When avoidance alone is insufficient, topical corticosteroids are the usual first-line treatment for localized PACD. When steroid-sparing treatments are preferred, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used. If PACD is more widespread and severe, systemic therapy using steroids or steroid-sparing agents may be necessary to provide symptomatic relief.4

Final Interpretation

Photoallergic contact dermatitis is not uncommon, particularly among photosensitive patients. Most cases are due to sunscreens or topical NSAIDs. Consideration of PPT should be given in any patient with a chronic photodistributed dermatitis to evaluate for the possibility of PACD.

Photoallergic contact dermatitis (PACD), a subtype of allergic contact dermatitis that occurs because of the specific combination of exposure to an exogenous chemical applied topically to the skin and UV radiation, may be more common than was once thought.1 Although the incidence in the general population is unknown, current research points to approximately 20% to 40% of patients with suspected photosensitivity having a PACD diagnosis.2 Recently, the North American Contact Dermatitis Group (NACDG) reported that 21% of 373 patients undergoing photopatch testing (PPT) were diagnosed with PACD2; however, PPT is not routinely performed, which may contribute to underdiagnosis.

Mechanism of Disease

Similar to allergic contact dermatitis, PACD is a delayed type IV hypersensitivity reaction; however, it only occurs when an exogenous chemical is applied topically to the skin with concomitant exposure to UV radiation, usually in the UVA range (315–400 nm).3,4 When exposed to UV radiation, it is thought that the exogenous chemical combines with a protein in the skin and transforms into a photoantigen. In the sensitization phase, the photoantigen is taken up by antigen-presenting cells in the epidermis and transported to local lymph nodes where antigen-specific T cells are generated.5 In the elicitation phase, the inflammatory reaction of PACD occurs upon subsequent exposure to the same chemical plus UV radiation.4 Development of PACD does not necessarily depend on the dose of the chemical or the amount of UV radiation.6 Why certain individuals may be more susceptible is unknown, though major histocompatibility complex haplotypes could be influential.7,8

Clinical Manifestations

Photoallergic contact dermatitis primarily presents in sun-exposed areas of the skin (eg, face, neck, V area of the chest, dorsal upper extremities) with sparing of naturally photoprotected sites, such as the upper eyelids and nasolabial and retroauricular folds. Other than its characteristic photodistribution, PACD often is clinically indistinguishable from routine allergic contact dermatitis. It manifests as a pruritic, poorly demarcated, eczematous or sometimes vesiculobullous eruption that develops in a delayed fashion—24 to 72 hours after sun exposure. The dermatitis may extend to other parts of the body either through spread of the chemical agent by the hands or clothing or due to the systemic nature of the immune response. The severity of the presentation can vary depending on multiple factors, such as concentration and absorption of the agent, length of exposure, intensity and duration of UV radiation exposure, and individual susceptibility.4 Chronic PACD may become lichenified. Generally, rashes resolve after discontinuation of the causative agent; however, long-term exposure may lead to development of chronic actinic dermatitis, with persistent photodistributed eczema regardless of contact with the initial inciting agent.9

Differential Diagnosis

The differential diagnosis for patients presenting with photodistributed dermatitis is broad; therefore, taking a thorough history is important. Considerations include age of onset, timing and persistence of reactions, use of topical and systemic medications (both prescription and over-the-counter [OTC]), personal care products, occupation, and hobbies, as well as a thorough review of systems.

It is important to distinguish PACD from phototoxic contact dermatitis (PTCD)(also known as photoirritant contact dermatitis)(Table). Asking about the onset and timing of the eruption may be critical for distinction, as PTCD can occur within minutes to hours of the first exposure to a chemical and UV radiation, while there is a sensitization delay in PACD.6 Phytophotodermatitis is a well-known type of PTCD caused by exposure to furocoumarin-containing plants, most commonly limes.10 Other causes of PTCD include tar products and certain medications.11 Importantly, PPT to a known phototoxic chemical should never be performed because it will cause a strong reaction in anyone tested, regardless of exposure history.

Comparison of Phototoxic and Photoallergic Contact Dermatitis


Other diagnoses to consider include photoaggravated dermatoses (eg, atopic dermatitis, lupus erythematosus, dermatomyositis) and idiopathic photodermatoses (eg, chronic actinic dermatitis, actinic prurigo, polymorphous light eruption). Although atopic dermatitis usually improves with UV light exposure, photoaggravated atopic dermatitis is suggested in eczema patients who flare with sun exposure, in a seasonal pattern, or after phototherapy; this condition is challenging to differentiate from PACD if PPT is not performed.12 The diagnosis of idiopathic photodermatoses is nuanced; however, asking about the timeline of the reaction including onset, duration, and persistence, as well as characterization of unique clinical features, can help in differentiation.13 In certain scenarios, a biopsy may be helpful. A thorough review of systems will help to assess for autoimmune connective tissue disorders, and relevant serologies should be checked as indicated.

Diagnosis

Histologically, PACD presents similarly to allergic contact dermatitis with spongiotic dermatitis; therefore, biopsy cannot be relied upon to make the diagnosis.6 Photopatch testing is required for definitive diagnosis. It is reasonable to perform PPT in any patient with chronic dermatitis primarily affecting sun-exposed areas without a clear alternative diagnosis.14,15 Of note, at present there are no North American consensus guidelines for PPT, but typically duplicate sets of photoallergens are applied to both sides of the patient’s back and one side is exposed to UVA radiation. The reactions are compared after 48 to 96 hours.15 A positive reaction only at the irradiated site is consistent with photoallergy, while a reaction of equal strength at both the irradiated and nonirradiated sites indicates regular contact allergy. The case of a reaction occurring at both sites with a stronger response at the irradiated site is known as photoaggravated contact allergy, which can be thought of as allergic contact dermatitis that worsens but does not solely occur with exposure to sunlight.

 

 

Although PPT is necessary for the accurate diagnosis of PACD, it is infrequently used. Two surveys of 112 and 117 American Contact Dermatitis Society members, respectively, have revealed that only around half performed PPT, most of them testing fewer than 20 times per year.16,17 Additionally, there was variability in the test methodology and allergens employed. Nevertheless, most respondents tested sunscreens, nonsteroidal anti-inflammatory drugs (NSAIDs), fragrances, and their patients’ own products.16,17 The most common reasons for not performing PPT were lack of equipment, insufficient skills, rare clinical suspicion, and cost. Dermatologists at academic centers performed more PPT than those in other practice settings, including multispecialty group practices and private offices.16 These findings highlight multiple factors that may contribute to reduced patient access to PPT and thus potential underdiagnosis of PACD.

Common Photoallergens

The most common photoallergens change over time in response to market trends; for example, fragrance was once a top photoallergen in the United States in the 1970s and 1980s but declined in prominence after musk ambrette—the primary allergen associated with PACD at the time—was removed as an ingredient in fragrances.18

In the largest and most recent PPT series from North America (1999-2009),2 sunscreens comprised 7 of the top 10 most common photoallergens, which is consistent with other studies showing sunscreens to be the most common North American photoallergens.19-22 The frequency of PACD due to sunscreens likely relates to their increasing use worldwide as awareness of photocarcinogenesis and photoaging grows, as well as the common use of UV filters in nonsunscreen personal care products, ranging from lip balms to perfumes and bodywashes. Chemical (organic) UV filters—in particular oxybenzone (benzophenone-3) and avobenzone (butyl methoxydibenzoylmethane)—are the most common sunscreen photoallergens.2,23 Para-aminobenzoic acid was once a common photoallergen, but it is no longer used in US sunscreens due to safety concerns.19,20 The physical (inorganic) UV filters zinc oxide and titanium dioxide are not known photosensitizers.

Methylisothiazolinone (MI) is a highly allergenic preservative commonly used in a wide array of personal care products, including sunscreens.24 In the most recent NACDG patch test data, MI was the second most common contact allergen.25 Allergic contact dermatitis caused by MI in sunscreen can mimic PACD.26 In addition, MI can cause photoaggravated contact dermatitis, with some affected patients experiencing ongoing photosensitivity even after avoiding this allergen.26-30 The European Union and Canada have introduced restrictions on the use of MI in personal care products, but no such regulatory measures have been taken in the United States to date.25,31,32

After sunscreens, another common cause of PACD are topical NSAIDs, which are frequently used for musculoskeletal pain relief. These are of particular concern in Europe, where a variety of formulations are widely available OTC.33 Ketoprofen and etofenamate are responsible for the largest number of PACD reactions in Europe.2,34,35 Meanwhile, the only OTC topical NSAID available in the United States is diclofenac gel, which was approved in 2020. Cases of PACD due to use of diclofenac gel have been reported in the literature, but testing in larger populations is needed.36-39

Notably, ketoprofen may co- or cross-react with certain UV filters—oxybenzone and octocrylene—and the lipid-lowering agent fenofibrate due to chemical similarities.40-43 Despite the relatively high number of photoallergic reactions to ketoprofen in the NACDG photopatch series, only 25% (5/20) were considered clinically relevant (ie, the allergen could not be verified as present in the known skin contactants of the patient, and the patient was not exposed to circumstances in which contact with materials known to contain the allergen would likely occur), which suggests that they likely represented cross-reactions in patients sensitized to sunscreens.2

Other agents that may cause PACD include antimicrobials, plants and plant derivatives, and pesticides.2,4,18 The antimicrobial fentichlor is a common cause of positive PPT reactions, but it rarely is clinically relevant.44

Treatment

The primary management of PACD centers on identification of the causative photoallergen to avoid future exposure. Patients should be educated on the various names by which the causative allergen can be identified on product labels and should be given a list of safe products that are free from relevant allergens and cross-reacting chemicals.45 Additionally, sun protection education should be provided. Exposure to UVA radiation can occur through windows, making the use of broad-spectrum sunscreens and protective clothing crucial. In cases of sunscreen-induced PACD, the responsible chemical UV filter(s) should be avoided, or alternatively, patients may use physical sunscreens containing only zinc oxide and/or titanium dioxide as active ingredients, as these are not known to cause PACD.4

When avoidance alone is insufficient, topical corticosteroids are the usual first-line treatment for localized PACD. When steroid-sparing treatments are preferred, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used. If PACD is more widespread and severe, systemic therapy using steroids or steroid-sparing agents may be necessary to provide symptomatic relief.4

Final Interpretation

Photoallergic contact dermatitis is not uncommon, particularly among photosensitive patients. Most cases are due to sunscreens or topical NSAIDs. Consideration of PPT should be given in any patient with a chronic photodistributed dermatitis to evaluate for the possibility of PACD.

References
  1. Darvay A, White IR, Rycroft RJ, et al. Photoallergic contact dermatitis is uncommon. Br J Dermatol. 2001;145:597-601.
  2. DeLeo VA, Adler BL, Warshaw EM, et al. Photopatch test results of the North American contact dermatitis group, 1999-2009. Photodermatol Photoimmunol Photomed. 2022;38:288-291.
  3. Kerr A, Ferguson J. Photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed. 2010;26:56-65.
  4. As¸kın Ö, Cesur SK, Engin B, et al. Photoallergic contact dermatitis. Curr Derm Rep. 2019;8:157-163.
  5. Wilm A, Berneburg M. Photoallergy. J Dtsch Dermatol Ges. 2015;13:7-13.
  6. DeLeo VA. Photocontact dermatitis. Dermatol Ther. 2004;17:279-288. 
  7. Imai S, Atarashi K, Ikesue K, et al. Establishment of murine model of allergic photocontact dermatitis to ketoprofen and characterization of pathogenic T cells. J Dermatol Sci. 2006;41:127-136.
  8. Tokura Y, Yagi H, Satoh T, et al. Inhibitory effect of melanin pigment on sensitization and elicitation of murine contact photosensitivity: mechanism of low responsiveness in C57BL/10 background mice. J Invest Dermatol. 1993;101:673-678.
  9. Stein KR, Scheinfeld NS. Drug-induced photoallergic and phototoxic reactions. Expert Opin Drug Saf. 2007;6:431-443.
  10. Janusz SC, Schwartz RA. Botanical briefs: phytophotodermatitis is an occupational and recreational dermatosis in the limelight. Cutis. 2021;107:187-189.
  11. Atwal SK, Chen A, Adler BL. Phototoxic contact dermatitis from over-the-counter 8-methoxypsoralen. Cutis. 2022;109:E2-E3.
  12. Rutter KJ, Farrar MD, Marjanovic EJ, et al. Clinicophotobiological characterization of photoaggravated atopic dermatitis [published online July 27, 2022]. JAMA Dermatol. doi:10.1001/jamadermatol.2022.2823
  13. Lecha M. Idiopathic photodermatoses: clinical, diagnostic and therapeutic aspects. J Eur Acad Dermatol Venereol. 2001;15:499-505.
  14. Marks JG Jr, Anderson BE, DeLeo VA. Contact & Occupational Dermatology. 4th ed. Jaypee Brothers; 2016.
  15. Bruynzeel DP, Ferguson J, Andersen K, et al. Photopatch testing: a consensus methodology for Europe. J Eur Acad Dermatol Venereol. 2004;18:679-682. 
  16. Kim T, Taylor JS, Maibach HI, et al. Photopatch testing among members of the American Contact Dermatitis Society. Dermatitis. 2020;31:59-67.
  17. Asemota E, Crawford G, Kovarik C, et al. A survey examining photopatch test and phototest methodologies of contact dermatologists in the United States: platform for developing a consensus. Dermatitis. 2017;28:265-269.
  18. Scalf LA, Davis MD, Rohlinger AL, et al. Photopatch testing of 182 patients: a 6-year experience at the Mayo Clinic. Dermatitis. 2009;20:44-52.
  19. Greenspoon J, Ahluwalia R, Juma N, et al. Allergic and photoallergic contact dermatitis: a 10-year experience. Dermatitis. 2013;24:29-32.
  20. Victor FC, Cohen DE, Soter NA. A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis. J Am Acad Dermatol. 2010;62:605-610.
  21. Schauder S, Ippen H. Contact and photocontact sensitivity to sunscreens. review of a 15-year experience and of the literature. Contact Dermatitis. 1997;37:221-232. 
  22. Collaris EJ, Frank J. Photoallergic contact dermatitis caused by ultraviolet filters in different sunscreens. Int J Dermatol. 2008;47(suppl 1):35-37.
  23. Heurung AR, Raju SI, Warshaw EM. Adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management. Dermatitis. 2014;25:289-326.
  24. Reeder M, Atwater AR. Methylisothiazolinone and isothiazolinone allergy. Cutis. 2019;104:94-96.
  25. DeKoven JG, Silverberg JI, Warshaw EM, et al. North American Contact Dermatitis Group Patch Test Results: 2017-2018. Dermatitis. 2021;32:111-123.
  26. Kullberg SA, Voller LM, Warshaw EM. Methylisothiazolinone in “dermatology-recommended” sunscreens: an important mimicker of photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed. 2021;37:366-370. 
  27. Herman A, Aerts O, de Montjoye L, et al. Isothiazolinone derivatives and allergic contact dermatitis: a review and update. J Eur Acad Dermatol Venereol. 2019;33:267-276.
  28. Adler BL, Houle MC, Pratt M. Photoaggravated contact dermatitis to methylisothiazolinone and associated photosensitivity: a case series [published online January 25, 2022]. Dermatitis. doi:10.1097/DER.0000000000000833
  29. Aerts O, Goossens A, Marguery MC, et al. Photoaggravated allergic contact dermatitis and transient photosensitivity caused by methylisothiazolinone. Contact Dermatitis. 2018;78:241-245.
  30. Pirmez R, Fernandes AL, Melo MG. Photoaggravated contact dermatitis to Kathon CG (methylchloroisothiazolinone/methylisothiazolinone): a novel pattern of involvement in a growing epidemic?. Br J Dermatol. 2015;173:1343-1344.
  31. Uter W, Aalto-Korte K, Agner T, et al. The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.J Eur Acad Dermatol Venereol. 2020;34:333-339.
  32. Government of Canada. Changes to the cosmetic ingredient hotlist. December 3, 2019. Updated August 26, 2022. Accessed October 20, 2022. https://www.canada.ca/en/health-canada/services/consumer-product-safety/cosmetics/cosmetic-ingredient-hotlist-prohibited-restricted-ingredients/changes.html
  33. Barkin RL. Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther. 2015;22:388-407.
  34. European Multicentre Photopatch Test Study (EMCPPTS) Taskforce. A European multicentre photopatch test study. Br J Dermatol. 2012;166:1002-1009.
  35. Ophaswongse S, Maibach H. Topical nonsteroidal antiinflammatory drugs: allergic and photoallergic contact dermatitis and phototoxicity. Contact Dermatitis. 1993;29:57-64. 
  36. Kowalzick L, Ziegler H. Photoallergic contact dermatitis from topical diclofenac in Solaraze gel. Contact Dermatitis. 2006;54:348-349.
  37. Montoro J, Rodríguez M, Díaz M, et al. Photoallergic contact dermatitis due to diclofenac. Contact Dermatitis. 2003;48:115.
  38. Fernández-Jorge B, Goday-Buján JJ, Murga M, et al. Photoallergic contact dermatitis due to diclofenac with cross-reaction to aceclofenac: two case reports. Contact Dermatitis. 2009;61:236-237.
  39. Akat PB. Severe photosensitivity reaction induced by topical diclofenac. Indian J Pharmacol. 2013;45:408-409.
  40. Leroy D, Dompmartin A, Szczurko C, et al. Photodermatitis from ketoprofen with cross-reactivity to fenofibrate and benzophenones. Photodermatol Photoimmunol Photomed. 1997;13:93-97.
  41. Devleeschouwer V, Roelandts R, Garmyn M, et al. Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients. Contact Dermatitis. 2008;58:159-166.
  42. Matsushita T, Kamide R. Five cases of photocontact dermatitisdue to topical ketoprofen: photopatch testing and cross-reaction study. Photodermatol Photoimmunol Photomed. 2001;17:26-31.
  43. de Groot AC, Roberts DW. Contact and photocontact allergy to octocrylene: a review. Contact Dermatitis. 2014;70:193-204.
  44. Wolverton JE, Soter NA, Cohen DE. Fentichlor photocontact dermatitis: a persistent enigma. Dermatitis. 2013;24:77-81.
  45. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient management and education. J Am Acad Dermatol. 2016;74:1043-1054.
References
  1. Darvay A, White IR, Rycroft RJ, et al. Photoallergic contact dermatitis is uncommon. Br J Dermatol. 2001;145:597-601.
  2. DeLeo VA, Adler BL, Warshaw EM, et al. Photopatch test results of the North American contact dermatitis group, 1999-2009. Photodermatol Photoimmunol Photomed. 2022;38:288-291.
  3. Kerr A, Ferguson J. Photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed. 2010;26:56-65.
  4. As¸kın Ö, Cesur SK, Engin B, et al. Photoallergic contact dermatitis. Curr Derm Rep. 2019;8:157-163.
  5. Wilm A, Berneburg M. Photoallergy. J Dtsch Dermatol Ges. 2015;13:7-13.
  6. DeLeo VA. Photocontact dermatitis. Dermatol Ther. 2004;17:279-288. 
  7. Imai S, Atarashi K, Ikesue K, et al. Establishment of murine model of allergic photocontact dermatitis to ketoprofen and characterization of pathogenic T cells. J Dermatol Sci. 2006;41:127-136.
  8. Tokura Y, Yagi H, Satoh T, et al. Inhibitory effect of melanin pigment on sensitization and elicitation of murine contact photosensitivity: mechanism of low responsiveness in C57BL/10 background mice. J Invest Dermatol. 1993;101:673-678.
  9. Stein KR, Scheinfeld NS. Drug-induced photoallergic and phototoxic reactions. Expert Opin Drug Saf. 2007;6:431-443.
  10. Janusz SC, Schwartz RA. Botanical briefs: phytophotodermatitis is an occupational and recreational dermatosis in the limelight. Cutis. 2021;107:187-189.
  11. Atwal SK, Chen A, Adler BL. Phototoxic contact dermatitis from over-the-counter 8-methoxypsoralen. Cutis. 2022;109:E2-E3.
  12. Rutter KJ, Farrar MD, Marjanovic EJ, et al. Clinicophotobiological characterization of photoaggravated atopic dermatitis [published online July 27, 2022]. JAMA Dermatol. doi:10.1001/jamadermatol.2022.2823
  13. Lecha M. Idiopathic photodermatoses: clinical, diagnostic and therapeutic aspects. J Eur Acad Dermatol Venereol. 2001;15:499-505.
  14. Marks JG Jr, Anderson BE, DeLeo VA. Contact & Occupational Dermatology. 4th ed. Jaypee Brothers; 2016.
  15. Bruynzeel DP, Ferguson J, Andersen K, et al. Photopatch testing: a consensus methodology for Europe. J Eur Acad Dermatol Venereol. 2004;18:679-682. 
  16. Kim T, Taylor JS, Maibach HI, et al. Photopatch testing among members of the American Contact Dermatitis Society. Dermatitis. 2020;31:59-67.
  17. Asemota E, Crawford G, Kovarik C, et al. A survey examining photopatch test and phototest methodologies of contact dermatologists in the United States: platform for developing a consensus. Dermatitis. 2017;28:265-269.
  18. Scalf LA, Davis MD, Rohlinger AL, et al. Photopatch testing of 182 patients: a 6-year experience at the Mayo Clinic. Dermatitis. 2009;20:44-52.
  19. Greenspoon J, Ahluwalia R, Juma N, et al. Allergic and photoallergic contact dermatitis: a 10-year experience. Dermatitis. 2013;24:29-32.
  20. Victor FC, Cohen DE, Soter NA. A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis. J Am Acad Dermatol. 2010;62:605-610.
  21. Schauder S, Ippen H. Contact and photocontact sensitivity to sunscreens. review of a 15-year experience and of the literature. Contact Dermatitis. 1997;37:221-232. 
  22. Collaris EJ, Frank J. Photoallergic contact dermatitis caused by ultraviolet filters in different sunscreens. Int J Dermatol. 2008;47(suppl 1):35-37.
  23. Heurung AR, Raju SI, Warshaw EM. Adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management. Dermatitis. 2014;25:289-326.
  24. Reeder M, Atwater AR. Methylisothiazolinone and isothiazolinone allergy. Cutis. 2019;104:94-96.
  25. DeKoven JG, Silverberg JI, Warshaw EM, et al. North American Contact Dermatitis Group Patch Test Results: 2017-2018. Dermatitis. 2021;32:111-123.
  26. Kullberg SA, Voller LM, Warshaw EM. Methylisothiazolinone in “dermatology-recommended” sunscreens: an important mimicker of photoallergic contact dermatitis. Photodermatol Photoimmunol Photomed. 2021;37:366-370. 
  27. Herman A, Aerts O, de Montjoye L, et al. Isothiazolinone derivatives and allergic contact dermatitis: a review and update. J Eur Acad Dermatol Venereol. 2019;33:267-276.
  28. Adler BL, Houle MC, Pratt M. Photoaggravated contact dermatitis to methylisothiazolinone and associated photosensitivity: a case series [published online January 25, 2022]. Dermatitis. doi:10.1097/DER.0000000000000833
  29. Aerts O, Goossens A, Marguery MC, et al. Photoaggravated allergic contact dermatitis and transient photosensitivity caused by methylisothiazolinone. Contact Dermatitis. 2018;78:241-245.
  30. Pirmez R, Fernandes AL, Melo MG. Photoaggravated contact dermatitis to Kathon CG (methylchloroisothiazolinone/methylisothiazolinone): a novel pattern of involvement in a growing epidemic?. Br J Dermatol. 2015;173:1343-1344.
  31. Uter W, Aalto-Korte K, Agner T, et al. The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.J Eur Acad Dermatol Venereol. 2020;34:333-339.
  32. Government of Canada. Changes to the cosmetic ingredient hotlist. December 3, 2019. Updated August 26, 2022. Accessed October 20, 2022. https://www.canada.ca/en/health-canada/services/consumer-product-safety/cosmetics/cosmetic-ingredient-hotlist-prohibited-restricted-ingredients/changes.html
  33. Barkin RL. Topical nonsteroidal anti-inflammatory drugs: the importance of drug, delivery, and therapeutic outcome. Am J Ther. 2015;22:388-407.
  34. European Multicentre Photopatch Test Study (EMCPPTS) Taskforce. A European multicentre photopatch test study. Br J Dermatol. 2012;166:1002-1009.
  35. Ophaswongse S, Maibach H. Topical nonsteroidal antiinflammatory drugs: allergic and photoallergic contact dermatitis and phototoxicity. Contact Dermatitis. 1993;29:57-64. 
  36. Kowalzick L, Ziegler H. Photoallergic contact dermatitis from topical diclofenac in Solaraze gel. Contact Dermatitis. 2006;54:348-349.
  37. Montoro J, Rodríguez M, Díaz M, et al. Photoallergic contact dermatitis due to diclofenac. Contact Dermatitis. 2003;48:115.
  38. Fernández-Jorge B, Goday-Buján JJ, Murga M, et al. Photoallergic contact dermatitis due to diclofenac with cross-reaction to aceclofenac: two case reports. Contact Dermatitis. 2009;61:236-237.
  39. Akat PB. Severe photosensitivity reaction induced by topical diclofenac. Indian J Pharmacol. 2013;45:408-409.
  40. Leroy D, Dompmartin A, Szczurko C, et al. Photodermatitis from ketoprofen with cross-reactivity to fenofibrate and benzophenones. Photodermatol Photoimmunol Photomed. 1997;13:93-97.
  41. Devleeschouwer V, Roelandts R, Garmyn M, et al. Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients. Contact Dermatitis. 2008;58:159-166.
  42. Matsushita T, Kamide R. Five cases of photocontact dermatitisdue to topical ketoprofen: photopatch testing and cross-reaction study. Photodermatol Photoimmunol Photomed. 2001;17:26-31.
  43. de Groot AC, Roberts DW. Contact and photocontact allergy to octocrylene: a review. Contact Dermatitis. 2014;70:193-204.
  44. Wolverton JE, Soter NA, Cohen DE. Fentichlor photocontact dermatitis: a persistent enigma. Dermatitis. 2013;24:77-81.
  45. Mowad CM, Anderson B, Scheinman P, et al. Allergic contact dermatitis: patient management and education. J Am Acad Dermatol. 2016;74:1043-1054.
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Practice Points

  • Photoallergic contact dermatitis (PACD) presents clinically and histologically similar to allergic contact dermatitis but is concentrated in sun-exposed body sites.
  • Sunscreens currently are the most common photoallergens in North America, whereas topical nonsteroidal anti-inflammatory drugs are more common culprits in Europe.
  • Photopatch testing is required to diagnose PACD; however, it is infrequently performed, and there currently are no North American consensus guidelines.
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Update on Tinea Capitis Diagnosis and Treatment

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.1 Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.2

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion3:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.4

 

 

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.5Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.6Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.4

A, A 10-year-old boy with the black dot type of tinea capitis. B, Trichoscopy showed black dot hairs (pink circle), comma hairs (red arrows), corkscrew hairs (green arrows), short broken hairs (blue arrow), and perifollicular scaling (yellow arrow).
A, A 10-year-old boy with the black dot type of tinea capitis. B, Trichoscopy showed black dot hairs (pink circle), comma hairs (red arrows), corkscrew hairs (green arrows), short broken hairs (blue arrow), and perifollicular scaling (yellow arrow). C, Clinical resolution was achieved after 8 weeks of griseofulvin therapy. D, Posttreatment trichoscopy showed disappearance of dystrophic hairs.

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.7

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.9

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.10In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.9The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.11 The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.12 In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.13

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.14

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

References
  1. Leung AKC, Hon KL, Leong KF, et al. Tinea capitis: an updated review. Recent Pat Inflamm Allergy Drug Discov. 2020;14:58-68.
  2. Abdel-Rahman SM, Preuett BL. Genetic predictors of susceptibility to cutaneous fungal infections: a pilot genome wide association study to refine a candidate gene search. J Dermatol Sci. 2012;67:147-152.
  3. Hay RJ. Tinea capitis: current status. Mycopathologia. 2017;182:87-93.
  4. Wahbah HR, Atallah RB, Eldahshan RM, et al. A prospective clinical and trichoscopic study of tinea capitis in children during treatment [published online May 23, 2022]. Dermatol Ther. 2022;35:E15582. doi:10.1111/dth.15582
  5. Salehi Z, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Molecular epidemiology, genetic diversity, and antifungal susceptibility of major pathogenic dermatophytes isolated from human dermatophytosis. Front Microbiol. 2021;12:643509.
  6. Lamisil. Package insert. Novartis; 2011. Accessed October 17, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf
  7. Gupta AK, Drummond-Main C. Meta-analysis of randomized, controlled trials comparing particular doses of griseofulvin and terbinafine for the treatment of tinea capitis. Pediatr Dermatol. 2013;30:1-6.
  8. Tey HL, Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. J Am Acad Dermatol. 2011;64:663-670.
  9. Gupta AK, Friedlander SF, Simkovich AJ. Tinea capitis: an update. Pediatr Dermatol. 2022;39:167-172.
  10. Aspiroz C, Melcon B, Cerro PA, et al. Tinea capitis caused by Microsporum canis treated with methyl-aminolevulinate daylight photodynamic therapy and ketoconazole shampooing. Photodermatol Photoimmunol Photomed. 2021;37:567-568.
  11. Aleohin N, Bar J, Bar-Ilan E, et al. Laboratory monitoring during antifungal treatment of paediatric tinea capitis. Mycoses. 2021;64:157-161.
  12. Kimberlin DW, Brady MT, Jackson MA, et al, eds. Tinea capitis. In: Red Book 2018-2021: Report of the Committee of Infectious Diseases. American Academy of Pediatrics; 2018:798-801.
  13. Bortolussi R, Martin S, Audcent T, et al. Antifungal agents for common outpatient paediatric infections. Canadian Paediatric Society website. Published June 20, 2019. Accessed October 4, 2022. https://www.cps.ca/en/documents/position/antifungal-agents-common-infections
  14. Tao R, Zhu P, Zhou Y, et al. Altered skin fungal and bacterial community compositions in tinea capitis. Mycoses. 2022;65:834-840.
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Correspondence: Mohamed L. Elsaie, MD ([email protected]).

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From the Department of Dermatology, Medical and Clinical Research Institute, National Research Centre, Egypt, and the Miller School of Medicine, University of Miami, Florida.

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Correspondence: Mohamed L. Elsaie, MD ([email protected]).

Author and Disclosure Information

From the Department of Dermatology, Medical and Clinical Research Institute, National Research Centre, Egypt, and the Miller School of Medicine, University of Miami, Florida.

The author reports no conflict of interest.

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Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.1 Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.2

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion3:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.4

 

 

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.5Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.6Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.4

A, A 10-year-old boy with the black dot type of tinea capitis. B, Trichoscopy showed black dot hairs (pink circle), comma hairs (red arrows), corkscrew hairs (green arrows), short broken hairs (blue arrow), and perifollicular scaling (yellow arrow).
A, A 10-year-old boy with the black dot type of tinea capitis. B, Trichoscopy showed black dot hairs (pink circle), comma hairs (red arrows), corkscrew hairs (green arrows), short broken hairs (blue arrow), and perifollicular scaling (yellow arrow). C, Clinical resolution was achieved after 8 weeks of griseofulvin therapy. D, Posttreatment trichoscopy showed disappearance of dystrophic hairs.

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.7

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.9

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.10In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.9The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.11 The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.12 In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.13

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.14

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

Tinea capitis (TC) most often is caused by Trichophyton tonsurans and Microsporum canis. The peak incidence is between 3 and 7 years of age. Noninflammatory TC typically presents as fine scaling with single or multiple scaly patches of circular alopecia (grey patches); diffuse or patchy, fine, white, adherent scaling of the scalp resembling generalized dandruff with subtle hair loss; or single or multiple patches of well-demarcated areas of alopecia with fine scale studded with broken-off hairs at the scalp surface, resulting in a black dot appearance. Inflammatory variants of TC include kerion and favus.1 Herein, updates on diagnosis, treatment, and monitoring of TC are provided, as well as a discussion of changes in the fungal microbiome associated with TC. Lastly, insights to some queries that practitioners may encounter when treating children with TC are provided.

Genetic Susceptibility

Molecular techniques have identified a number of macrophage regulator, leukocyte activation and migration, and cutaneous permeability genes associated with susceptibility to TC. These findings indicate that genetically determined deficiency in adaptive immune responses may affect the predisposition to dermatophyte infections.2

Clinical Varieties of Infection

Dermatophytes causing ringworm are capable of invading the hair shafts and can simultaneously invade smooth or glabrous skin (eg, T tonsurans, Trichophyton schoenleinii, Trichophyton violaceum). Some causative dermatophytes can even penetrate the nails (eg, Trichophyton soudanense). The clinical presentation is dependent on 3 main patterns of hair invasion3:

• Ectothrix: A mid-follicular pattern of invasion with hyphae growing down to the hair bulb that commonly is caused by Microsporum species. It clinically presents with scaling and inflammation with hair shafts breaking 2 to 3 mm above the scalp level.

• Endothrix: This pattern is nonfluorescent on Wood lamp examination, and hairs often break at the scalp level (black dot type). Trichophyton tonsurans, T soudanense, Trichophyton rubrum, and T violaceum are common causes.

• Favus: In this pattern, T schoenleinii is a common cause, and hairs grow to considerable lengths above the scalp with less damage than the other patterns. The hair shafts present with characteristic air spaces, and hyphae form clusters at the level of the epidermis.

Diagnosis

Optimal treatment of TC relies on proper identification of the causative agent. Fungal culture remains the gold standard of mycologic diagnosis regardless of its delayed results, which may take up to 4 weeks for proper identification of the fungal colonies and require ample expertise to interpret the morphologic features of the grown colonies.4

 

 

Other tests such as the potassium hydroxide preparation are nonspecific and do not identify the dermatophyte species. Although this method has been reported to have 5% to 15% false-negative results in routine practice depending on the skill of the observer and the quality of sampling, microscopic examination is essential, as it may allow the clinician to start treatment sooner pending culture results. The use of a Wood lamp is not suitable for definitive species identification, as this technique primarily is useful for observing fluorescence in ectothrix infection caused by Microsporum species, with the exception of T schoenleinii; otherwise, Trichophyton species, which cause endothrix infections, do not fluoresce.5Polymerase chain reaction is a sensitive technique that can help identify both the genus and species of common dermatophytes. Common target sequences include the ribosomal internal transcribed spacer and translation elongation factor 1α. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also has become popular for dermatophyte identification.6Trichoscopic diagnosis of TC, which is simple and noninvasive, is becoming increasingly popular. Features such as short, broken, black dot, comma, corkscrew, and/or zigzag hairs, as well as perifollicular scaling, are helpful for diagnosing TC (Figure). Moreover, trichoscopy can be useful for differentiating other common causes of hair loss, such as trichotillomania and alopecia areata. It had been reported that the trichoscopic features of TC can be seen as early as 2 weeks after starting treatment and therefore this can be a reliable period in which to follow-up with the patient to evaluate progress. The disappearance of black dots and comma hairs can be appreciated from 2 weeks onwards by trichoscopic evaluation.4

A, A 10-year-old boy with the black dot type of tinea capitis. B, Trichoscopy showed black dot hairs (pink circle), comma hairs (red arrows), corkscrew hairs (green arrows), short broken hairs (blue arrow), and perifollicular scaling (yellow arrow).
A, A 10-year-old boy with the black dot type of tinea capitis. B, Trichoscopy showed black dot hairs (pink circle), comma hairs (red arrows), corkscrew hairs (green arrows), short broken hairs (blue arrow), and perifollicular scaling (yellow arrow). C, Clinical resolution was achieved after 8 weeks of griseofulvin therapy. D, Posttreatment trichoscopy showed disappearance of dystrophic hairs.

Treatment

The common recommendation for first-line treatment of TC is the use of systemic antifungals with the use of a topical agent as an adjuvant to prevent the spread of fungal spores. For almost 6 decades, griseofulvin had been the gold-standard fungistatic used for treating TC in patients older than 2 years until the 2007 US Food and Drug Administration (FDA) approval of terbinafine fungicidal oral granules for treatment of TC in patients older than 4 years.7

Meta-analyses have demonstrated comparable efficacy for a 4-week course of terbinafine compared to 6 weeks of griseofulvin for TC based on the infectious organism. Terbinafine demonstrated superiority in treating T tonsurans and a similar efficacy in treating T violaceum, while griseofulvin was superior in treating M canis and other Microsporum species.8,9

The off-label use of fluconazole and itraconazole to treat TC is gaining popularity, with limited trials showing increased evidence of their effectiveness. There is not much clinical evidence to support the use of other oral antifungals, including the newer azoles such as voriconazole or posaconazole.9

Newer limited evidence has shown the off-label use of photodynamic therapy to be a promising alternative to systemic antifungal therapy in treating TC, pending validation by larger sample trials.10In my practice, I have found that severe cases of TC demonstrating inflammation or possible widespread id reactions are better treated with oral steroids. Ketoconazole shampoo or selenium sulfide used 2 to 3 times weekly to prevent spread in the early phases of therapy is a good adjunct to systemic treatment. Cases with kerions should be assessed for the possibility of a coexisting bacterial infection under the crusts, and if confirmed, antibiotics should be started.9The commonly used systemic antifungals generally are safe with a low side-effect profile, but there is a risk for hepatotoxicity. The FDA recommends that baseline alanine transaminase and aspartate transaminase levels should be obtained prior to beginning a terbinafine-based treatment regimen.11 The American Academy of Pediatrics has specifically stated that laboratory testing of serum hepatic enzymes is not a requirement if a griseofulvin-based regimen does not exceed 8 weeks; however, transaminase levels (alanine transaminase and aspartate transaminase) should be considered in patients using terbinafine at baseline or if treatment is prolonged beyond 4 to 6 weeks.12 In agreement with the FDA guidelines, the Canadian Pediatric Society has suggested that liver enzymes should be periodically monitored in patients being treated with terbinafine beyond 4 to 6 weeks.13

Changes in the Fungal Microbiome

Research has shown that changes in the fungal microbiome were associated with an altered bacterial community in patients with TC. During fungal infection, the relative abundances of Cutibacterium and Corynebacterium increased, and the relative abundance of Streptococcus decreased. In addition, some uncommon bacterial genera such as Herbaspirillum and Methylorubrum were detected on the scalp in TC.14

Carrier State

Carrier state is determined for those siblings and contacts of cases with a clinically normal scalp that are positive on culture. Those individuals could represent a potential reservoir responsible for contamination (or recontamination) of the patient as well as treatment failure. Opinions remain divided as to whether to use oral antifungal therapy in these carriers or maintain therapy on antifungal shampoos containing ketoconazole or povidone-iodine. Due to the paucity of available data, my experience has shown that it is sufficient to use antifungal shampoos for such carriers. In zoophilic infections, it is important to identify and treat the animal source.6-9

Final Thoughts

Successful treatment of TC requires accurate identification of the pathogen, which commonly is achieved via fungal culture. Despite its practical value, the conventional identification of dermatophytes based on morphologic features can be highly challenging due to the low positive rate and delayed results. Trichoscopy is a quick, handy, and noninvasive tool that can better indicate the diagnosis and also is helpful for follow-up on treatment progress. Due to better understanding of the immunology and genetic susceptibility associated with TC spread, the current treatment pipeline holds more insight into better control of this condition. Increased surveillance, prompt diagnosis, and early onset of systemic treatment are the key to proper prevention of spread of TC.

References
  1. Leung AKC, Hon KL, Leong KF, et al. Tinea capitis: an updated review. Recent Pat Inflamm Allergy Drug Discov. 2020;14:58-68.
  2. Abdel-Rahman SM, Preuett BL. Genetic predictors of susceptibility to cutaneous fungal infections: a pilot genome wide association study to refine a candidate gene search. J Dermatol Sci. 2012;67:147-152.
  3. Hay RJ. Tinea capitis: current status. Mycopathologia. 2017;182:87-93.
  4. Wahbah HR, Atallah RB, Eldahshan RM, et al. A prospective clinical and trichoscopic study of tinea capitis in children during treatment [published online May 23, 2022]. Dermatol Ther. 2022;35:E15582. doi:10.1111/dth.15582
  5. Salehi Z, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Molecular epidemiology, genetic diversity, and antifungal susceptibility of major pathogenic dermatophytes isolated from human dermatophytosis. Front Microbiol. 2021;12:643509.
  6. Lamisil. Package insert. Novartis; 2011. Accessed October 17, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf
  7. Gupta AK, Drummond-Main C. Meta-analysis of randomized, controlled trials comparing particular doses of griseofulvin and terbinafine for the treatment of tinea capitis. Pediatr Dermatol. 2013;30:1-6.
  8. Tey HL, Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. J Am Acad Dermatol. 2011;64:663-670.
  9. Gupta AK, Friedlander SF, Simkovich AJ. Tinea capitis: an update. Pediatr Dermatol. 2022;39:167-172.
  10. Aspiroz C, Melcon B, Cerro PA, et al. Tinea capitis caused by Microsporum canis treated with methyl-aminolevulinate daylight photodynamic therapy and ketoconazole shampooing. Photodermatol Photoimmunol Photomed. 2021;37:567-568.
  11. Aleohin N, Bar J, Bar-Ilan E, et al. Laboratory monitoring during antifungal treatment of paediatric tinea capitis. Mycoses. 2021;64:157-161.
  12. Kimberlin DW, Brady MT, Jackson MA, et al, eds. Tinea capitis. In: Red Book 2018-2021: Report of the Committee of Infectious Diseases. American Academy of Pediatrics; 2018:798-801.
  13. Bortolussi R, Martin S, Audcent T, et al. Antifungal agents for common outpatient paediatric infections. Canadian Paediatric Society website. Published June 20, 2019. Accessed October 4, 2022. https://www.cps.ca/en/documents/position/antifungal-agents-common-infections
  14. Tao R, Zhu P, Zhou Y, et al. Altered skin fungal and bacterial community compositions in tinea capitis. Mycoses. 2022;65:834-840.
References
  1. Leung AKC, Hon KL, Leong KF, et al. Tinea capitis: an updated review. Recent Pat Inflamm Allergy Drug Discov. 2020;14:58-68.
  2. Abdel-Rahman SM, Preuett BL. Genetic predictors of susceptibility to cutaneous fungal infections: a pilot genome wide association study to refine a candidate gene search. J Dermatol Sci. 2012;67:147-152.
  3. Hay RJ. Tinea capitis: current status. Mycopathologia. 2017;182:87-93.
  4. Wahbah HR, Atallah RB, Eldahshan RM, et al. A prospective clinical and trichoscopic study of tinea capitis in children during treatment [published online May 23, 2022]. Dermatol Ther. 2022;35:E15582. doi:10.1111/dth.15582
  5. Salehi Z, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Molecular epidemiology, genetic diversity, and antifungal susceptibility of major pathogenic dermatophytes isolated from human dermatophytosis. Front Microbiol. 2021;12:643509.
  6. Lamisil. Package insert. Novartis; 2011. Accessed October 17, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf
  7. Gupta AK, Drummond-Main C. Meta-analysis of randomized, controlled trials comparing particular doses of griseofulvin and terbinafine for the treatment of tinea capitis. Pediatr Dermatol. 2013;30:1-6.
  8. Tey HL, Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. J Am Acad Dermatol. 2011;64:663-670.
  9. Gupta AK, Friedlander SF, Simkovich AJ. Tinea capitis: an update. Pediatr Dermatol. 2022;39:167-172.
  10. Aspiroz C, Melcon B, Cerro PA, et al. Tinea capitis caused by Microsporum canis treated with methyl-aminolevulinate daylight photodynamic therapy and ketoconazole shampooing. Photodermatol Photoimmunol Photomed. 2021;37:567-568.
  11. Aleohin N, Bar J, Bar-Ilan E, et al. Laboratory monitoring during antifungal treatment of paediatric tinea capitis. Mycoses. 2021;64:157-161.
  12. Kimberlin DW, Brady MT, Jackson MA, et al, eds. Tinea capitis. In: Red Book 2018-2021: Report of the Committee of Infectious Diseases. American Academy of Pediatrics; 2018:798-801.
  13. Bortolussi R, Martin S, Audcent T, et al. Antifungal agents for common outpatient paediatric infections. Canadian Paediatric Society website. Published June 20, 2019. Accessed October 4, 2022. https://www.cps.ca/en/documents/position/antifungal-agents-common-infections
  14. Tao R, Zhu P, Zhou Y, et al. Altered skin fungal and bacterial community compositions in tinea capitis. Mycoses. 2022;65:834-840.
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ACC/AHA issues updated guidance on aortic disease

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Fri, 11/04/2022 - 13:50

The American College of Cardiology and the American Heart Association have published an updated guideline on the diagnosis and management of aortic disease, focusing on surgical intervention considerations, consistent imaging practices, genetic and familial screenings, and the importance of multidisciplinary care.

“There has been a host of new evidence-based research available for clinicians in the past decade when it comes to aortic disease. It was time to reevaluate and update the previous, existing guidelines,” Eric M. Isselbacher, MD, MSc, chair of the writing committee, said in a statement.

“We hope this new guideline can inform clinical practices with up-to-date and synthesized recommendations, targeted toward a full multidisciplinary aortic team working to provide the best possible care for this vulnerable patient population,” added Dr. Isselbacher, codirector of the Thoracic Aortic Center at Massachusetts General Hospital, Boston.

The 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease was simultaneously published online in the Journal of the American College of Cardiology and Circulation.

The new guideline replaces the 2010 ACCF/AHA Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease and the 2015 Surgery for Aortic Dilation in Patients With Bicuspid Aortic Valves: A Statement of Clarification From the ACC/AHA Task Force on Clinical Practice Guidelines.

The new guideline is intended to be used with the 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease.

It brings together guidelines for both the thoracic and abdominal aorta and is targeted to cardiovascular clinicians involved in the care of people with aortic disease, including general cardiovascular care clinicians and emergency medicine clinicians, the writing group says.

Among the key recommendations in the new guideline are the following:

  • Screen first-degree relatives of individuals diagnosed with aneurysms of the aortic root or ascending thoracic aorta, or those with aortic dissection to identify individuals most at risk for aortic disease. Screening would include genetic testing and imaging.
  • Be consistent in the way CT or MRI are obtained and reported; in the measurement of aortic size and features; and in how often images are used for monitoring before and after repair surgery or other intervention. Ideally, all surveillance imaging for an individual should be done using the same modality and in the same lab, the guideline notes.
  • For individuals who require aortic intervention, know that outcomes are optimized when surgery is performed by an experienced surgeon working in a multidisciplinary aortic team. The new guideline recommends “a specialized hospital team with expertise in the evaluation and management of aortic disease, in which care is delivered in a comprehensive, multidisciplinary manner.”
  • At centers with multidisciplinary aortic teams and experienced surgeons, the threshold for surgical intervention for sporadic aortic root and ascending aortic aneurysms has been lowered from 5.5 cm to 5.0 cm in select individuals, and even lower in specific scenarios among patients with heritable thoracic aortic aneurysms.
  • In patients who are significantly smaller or taller than average, surgical thresholds may incorporate indexing of the aortic root or ascending aortic diameter to either patient body surface area or height, or aortic cross-sectional area to patient height.
  • Rapid aortic growth is a risk factor for rupture and the definition for rapid aneurysm growth rate has been updated. Surgery is now recommended for patients with aneurysms of aortic root and ascending thoracic aorta with a confirmed growth rate of ≥ 0.3 cm per year across 2 consecutive years or ≥ 0.5 cm in 1 year.
  • In patients undergoing aortic root replacement surgery, valve-sparing aortic root replacement is reasonable if the valve is suitable for repair and when performed by experienced surgeons in a multidisciplinary aortic team.
  • Patients with acute type A aortic dissection, if clinically stable, should be considered for transfer to a high-volume aortic center to improve survival. The operative repair of type A aortic dissection should entail at least an open distal anastomosis rather than just a simple supracoronary interposition graft.
  • For management of uncomplicated type B aortic dissection, there is an increasing role for . Clinical trials of repair of thoracoabdominal aortic aneurysms with endografts are reporting results that suggest endovascular repair is an option for patients with suitable anatomy.
  • Shared decision-making between the patient and multidisciplinary aortic team is highly encouraged, especially when the patient is on the borderline of thresholds for repair or eligible for different types of surgical repair.
  • Shared decision-making should also be used with individuals who are pregnant or may become pregnant to consider the risks of pregnancy in individuals with aortic disease.

The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, the American College of Radiology, the Society of Cardiovascular Anesthesiologists, the Society for Cardiovascular Angiography and Interventions, the Society of Thoracic Surgeons, and the Society for Vascular Medicine.

It has been endorsed by the Society of Interventional Radiology and the Society for Vascular Surgery.

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

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The American College of Cardiology and the American Heart Association have published an updated guideline on the diagnosis and management of aortic disease, focusing on surgical intervention considerations, consistent imaging practices, genetic and familial screenings, and the importance of multidisciplinary care.

“There has been a host of new evidence-based research available for clinicians in the past decade when it comes to aortic disease. It was time to reevaluate and update the previous, existing guidelines,” Eric M. Isselbacher, MD, MSc, chair of the writing committee, said in a statement.

“We hope this new guideline can inform clinical practices with up-to-date and synthesized recommendations, targeted toward a full multidisciplinary aortic team working to provide the best possible care for this vulnerable patient population,” added Dr. Isselbacher, codirector of the Thoracic Aortic Center at Massachusetts General Hospital, Boston.

The 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease was simultaneously published online in the Journal of the American College of Cardiology and Circulation.

The new guideline replaces the 2010 ACCF/AHA Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease and the 2015 Surgery for Aortic Dilation in Patients With Bicuspid Aortic Valves: A Statement of Clarification From the ACC/AHA Task Force on Clinical Practice Guidelines.

The new guideline is intended to be used with the 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease.

It brings together guidelines for both the thoracic and abdominal aorta and is targeted to cardiovascular clinicians involved in the care of people with aortic disease, including general cardiovascular care clinicians and emergency medicine clinicians, the writing group says.

Among the key recommendations in the new guideline are the following:

  • Screen first-degree relatives of individuals diagnosed with aneurysms of the aortic root or ascending thoracic aorta, or those with aortic dissection to identify individuals most at risk for aortic disease. Screening would include genetic testing and imaging.
  • Be consistent in the way CT or MRI are obtained and reported; in the measurement of aortic size and features; and in how often images are used for monitoring before and after repair surgery or other intervention. Ideally, all surveillance imaging for an individual should be done using the same modality and in the same lab, the guideline notes.
  • For individuals who require aortic intervention, know that outcomes are optimized when surgery is performed by an experienced surgeon working in a multidisciplinary aortic team. The new guideline recommends “a specialized hospital team with expertise in the evaluation and management of aortic disease, in which care is delivered in a comprehensive, multidisciplinary manner.”
  • At centers with multidisciplinary aortic teams and experienced surgeons, the threshold for surgical intervention for sporadic aortic root and ascending aortic aneurysms has been lowered from 5.5 cm to 5.0 cm in select individuals, and even lower in specific scenarios among patients with heritable thoracic aortic aneurysms.
  • In patients who are significantly smaller or taller than average, surgical thresholds may incorporate indexing of the aortic root or ascending aortic diameter to either patient body surface area or height, or aortic cross-sectional area to patient height.
  • Rapid aortic growth is a risk factor for rupture and the definition for rapid aneurysm growth rate has been updated. Surgery is now recommended for patients with aneurysms of aortic root and ascending thoracic aorta with a confirmed growth rate of ≥ 0.3 cm per year across 2 consecutive years or ≥ 0.5 cm in 1 year.
  • In patients undergoing aortic root replacement surgery, valve-sparing aortic root replacement is reasonable if the valve is suitable for repair and when performed by experienced surgeons in a multidisciplinary aortic team.
  • Patients with acute type A aortic dissection, if clinically stable, should be considered for transfer to a high-volume aortic center to improve survival. The operative repair of type A aortic dissection should entail at least an open distal anastomosis rather than just a simple supracoronary interposition graft.
  • For management of uncomplicated type B aortic dissection, there is an increasing role for . Clinical trials of repair of thoracoabdominal aortic aneurysms with endografts are reporting results that suggest endovascular repair is an option for patients with suitable anatomy.
  • Shared decision-making between the patient and multidisciplinary aortic team is highly encouraged, especially when the patient is on the borderline of thresholds for repair or eligible for different types of surgical repair.
  • Shared decision-making should also be used with individuals who are pregnant or may become pregnant to consider the risks of pregnancy in individuals with aortic disease.

The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, the American College of Radiology, the Society of Cardiovascular Anesthesiologists, the Society for Cardiovascular Angiography and Interventions, the Society of Thoracic Surgeons, and the Society for Vascular Medicine.

It has been endorsed by the Society of Interventional Radiology and the Society for Vascular Surgery.

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

The American College of Cardiology and the American Heart Association have published an updated guideline on the diagnosis and management of aortic disease, focusing on surgical intervention considerations, consistent imaging practices, genetic and familial screenings, and the importance of multidisciplinary care.

“There has been a host of new evidence-based research available for clinicians in the past decade when it comes to aortic disease. It was time to reevaluate and update the previous, existing guidelines,” Eric M. Isselbacher, MD, MSc, chair of the writing committee, said in a statement.

“We hope this new guideline can inform clinical practices with up-to-date and synthesized recommendations, targeted toward a full multidisciplinary aortic team working to provide the best possible care for this vulnerable patient population,” added Dr. Isselbacher, codirector of the Thoracic Aortic Center at Massachusetts General Hospital, Boston.

The 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease was simultaneously published online in the Journal of the American College of Cardiology and Circulation.

The new guideline replaces the 2010 ACCF/AHA Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease and the 2015 Surgery for Aortic Dilation in Patients With Bicuspid Aortic Valves: A Statement of Clarification From the ACC/AHA Task Force on Clinical Practice Guidelines.

The new guideline is intended to be used with the 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease.

It brings together guidelines for both the thoracic and abdominal aorta and is targeted to cardiovascular clinicians involved in the care of people with aortic disease, including general cardiovascular care clinicians and emergency medicine clinicians, the writing group says.

Among the key recommendations in the new guideline are the following:

  • Screen first-degree relatives of individuals diagnosed with aneurysms of the aortic root or ascending thoracic aorta, or those with aortic dissection to identify individuals most at risk for aortic disease. Screening would include genetic testing and imaging.
  • Be consistent in the way CT or MRI are obtained and reported; in the measurement of aortic size and features; and in how often images are used for monitoring before and after repair surgery or other intervention. Ideally, all surveillance imaging for an individual should be done using the same modality and in the same lab, the guideline notes.
  • For individuals who require aortic intervention, know that outcomes are optimized when surgery is performed by an experienced surgeon working in a multidisciplinary aortic team. The new guideline recommends “a specialized hospital team with expertise in the evaluation and management of aortic disease, in which care is delivered in a comprehensive, multidisciplinary manner.”
  • At centers with multidisciplinary aortic teams and experienced surgeons, the threshold for surgical intervention for sporadic aortic root and ascending aortic aneurysms has been lowered from 5.5 cm to 5.0 cm in select individuals, and even lower in specific scenarios among patients with heritable thoracic aortic aneurysms.
  • In patients who are significantly smaller or taller than average, surgical thresholds may incorporate indexing of the aortic root or ascending aortic diameter to either patient body surface area or height, or aortic cross-sectional area to patient height.
  • Rapid aortic growth is a risk factor for rupture and the definition for rapid aneurysm growth rate has been updated. Surgery is now recommended for patients with aneurysms of aortic root and ascending thoracic aorta with a confirmed growth rate of ≥ 0.3 cm per year across 2 consecutive years or ≥ 0.5 cm in 1 year.
  • In patients undergoing aortic root replacement surgery, valve-sparing aortic root replacement is reasonable if the valve is suitable for repair and when performed by experienced surgeons in a multidisciplinary aortic team.
  • Patients with acute type A aortic dissection, if clinically stable, should be considered for transfer to a high-volume aortic center to improve survival. The operative repair of type A aortic dissection should entail at least an open distal anastomosis rather than just a simple supracoronary interposition graft.
  • For management of uncomplicated type B aortic dissection, there is an increasing role for . Clinical trials of repair of thoracoabdominal aortic aneurysms with endografts are reporting results that suggest endovascular repair is an option for patients with suitable anatomy.
  • Shared decision-making between the patient and multidisciplinary aortic team is highly encouraged, especially when the patient is on the borderline of thresholds for repair or eligible for different types of surgical repair.
  • Shared decision-making should also be used with individuals who are pregnant or may become pregnant to consider the risks of pregnancy in individuals with aortic disease.

The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, the American College of Radiology, the Society of Cardiovascular Anesthesiologists, the Society for Cardiovascular Angiography and Interventions, the Society of Thoracic Surgeons, and the Society for Vascular Medicine.

It has been endorsed by the Society of Interventional Radiology and the Society for Vascular Surgery.

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

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Pulmonologist consult at COPD admission reduces risk of return

Article Type
Changed
Mon, 11/14/2022 - 09:48

. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O2 saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

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. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O2 saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

. – If a pulmonologist becomes involved early in the care of patients admitted to the hospital for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), the rate of readmission is reduced substantially relative to no pulmonologist involvement, according to a retrospective cohort review presented at the annual meeting of the American College of Chest Physicians (CHEST).

“When stratified by severity of COPD at the time of admission, the difference in the readmission rate was even greater,” reported Nakisa Hekmat-Joo, MD, a third-year resident at Staten Island University Hospital, New York.

Just as protocols have been developed for prompt initiation of antibiotics in patients with septicemia or prompt revascularization in patients with ST-segment elevated myocardial infarction (STEMI), Dr. Hekmat-Joo said the data from this study warrant a larger trial to evaluate whether an AECOPD admission protocol is warranted to improve outcomes and lower costs.

In this study, all AECOPD admissions were included from a recent 2-year period at two Staten Island hospitals. Of these, 198 patients received a pulmonologist consult within 24 hours. The remaining 92 patients were not evaluated by pulmonologists but were admitted and then managed by residents, internists, or others.

The primary outcome was length of stay (LOS). Although the slightly lower LOS in pulmonologist-treated group did not approach significance (4.16 vs. 4.21 days; P = .88), the readmission rate at 90 days, which was a secondary outcome, was reduced by almost half (30.1% vs. 57.6%; P < .0001).

At admission, there was no significant difference between those receiving a pulmonologist consult and those who did not. The average O2 saturation was lower in the group seen by a pulmonologist (93% vs. 95.4%; P < .0001), but the most striking difference was the low relative readmission rate, which remained significant after controlling for severity and pulmonary function.

“When we stratified patients for baseline severity, the advantage of a pulmonologist consult was even greater for those with the most severe disease,” Dr. Hekmat-Joo said. Among those with the greatest severity, the 90-day readmission rate was nearly three times greater in the absence of a pulmonologist consult (72% vs. 28%).

Although the comparison of outcomes for those receiving a pulmonologist consult vs. those who did not was adjusted for COPD severity, the potential for pulmonologist consults to be ordered for those patients who looked the sickest would have likely worked against the study result.

“We speculate that pulmonologists were more likely than internists to treat beyond standard guidelines, particularly in the event of greater severity,” Dr. Hekmat-Joo explained. These steps might include earlier use of noninvasive positive pressure ventilation or earlier initiation of rehabilitation strategies.

There were several signals that a pulmonologist consult led to more rigorous care.

“The average time to follow-up after hospitalization was 23 days for the pulmonologist group and 66 days for the nonpulmonologist group,” said Dr. Hekmat-Joo, noting this difference was highly significant (P = .0052).

Based on these results, Dr. Hekmat-Joo and her co-investigators are now working on a protocol for COPD admissions that involves a pulmonologist consult within 24 hours of admission. She hopes to test this protocol in a prospective trial.

“COPD remains a major cause of death and consumes enormous health care resources. About 30% of the cost of COPD care is due to readmissions,” she said, noting that readmissions adversely impact quality of life.

Asked if there was sufficient staff at her institution to allow for a pulmonologist consult with every COPD admission, Dr. Hekmat-Joo acknowledged that this has to be demonstrated, but compelling evidence of a benefit might prompt a redistribution of resources.

“If we can show that readmissions are substantially reduced, adding staff to perform these consults would be a good investment,” said Dr. Hekmat-Joo, indicating that improved outcomes could also attract the attention of third-party payers and those tracking quality-of-care metrics.

There is a strong rationale for a randomized prospective trial to confirm the value of a pulmonologist consultation following admission for an acute exacerbation of COPD, according to Nicola A. Hanania, MD, director, Airways Clinical Research Center, Baylor College of Medicine, Houston.

The potential for benefit as seen in this retrospective study is a rational expectation and might be related to more appropriate therapy upon discharge as well as to earlier and more rigorous follow-up, according to Dr. Hanania. Although he cautioned that there is a meaningful risk of selection bias in a retrospective study, he thinks this study “is certainly probing an important issue.”

“Mortality from a hospitalized COPD exacerbation exceeds that of a myocardial infarction,” Dr. Hanania pointed out. Noting that all patients with an MI are evaluated by a cardiologist, he sees the logic of a pulmonologist consult – although he acknowledged that evidence is needed.

“I strongly believe that a prospective study is feasible and will answer the question in an unbiased manner if done properly,” he said in an interview. If a multicenter, well-controlled study was positive, it could change practice.

In the event of a study showing major clinical benefits, particularly a reduction in mortality, “I believe it is feasible to have a pulmonary consult to see every COPD exacerbation patient admitted to the hospital,” Dr. Hanania said.

Dr. Hekmat-Joo reports no relevant financial relationships. Dr. Hanania has financial relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan, Novartis, Regeneron, Sanofi, and Sunovion.

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

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Working while sick: Why doctors don’t stay home when ill

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Fri, 11/04/2022 - 13:19

Before the pandemic, physicians came to work sick, as people do in many other professions. The reasons are likely as varied as, “you weren’t feeling bad enough to miss work,” “you couldn’t afford to miss pay,” “you had too many patients to see,” or “too much work to do.”

In Medscape’s Employed Physicians Report: Loving the Focus, Hating the Bureaucracy, 61% of physicians reported that they sometimes or often come to work sick. Only 2% of respondents said they never come to work unwell.

Medscape wanted to know more about how often you call in sick, how often you come to work feeling unwell, what symptoms you have, and the dogma of your workplace culture regarding sick days. Not to mention the brutal ethos that starts in medical school, in which calling in sick shows weakness or is unacceptable.

So, we polled 2,347 physicians in the United States and abroad and asked them about their sniffling, sneezing, cold, flu, and fever symptoms, and, of course, COVID. Results were split about 50-50 among male and female physicians. The poll ran from Sept. 28 through Oct. 11.
 

Coming to work sick

It’s no surprise that the majority of physicians who were polled (85%) have come to work sick in 2022. In the last prepandemic year (2019), about 70% came to work feeling sick one to five times, and 13% worked while sick six to ten times.

When asked about the symptoms that they’ve previously come to work with, 48% of U.S. physicians said multiple symptoms. They gave high marks for runny nose, cough, congestion, and sore throat. Only 27% have worked with a fever, 22% have worked with other symptoms, and 7% have worked with both strep throat and COVID.

“My workplace, especially in the COVID years, accommodates persons who honestly do not feel well enough to report. Sooner or later, everyone covers for someone else who has to be out,” says Kenneth Abbott, MD, an oncologist in Maryland.
 

The culture of working while sick

Why doctors come to work when they’re sick is complicated. The overwhelming majority of U.S. respondents cited professional obligations; 73% noted that they feel a professional obligation to their patients, and 72% feel a professional obligation to their co-workers. Half of the polled U.S. physicians said they didn’t feel bad enough to stay home, while 48% said they had too much work to do to stay home.

Some 45% said the expectation at their workplace is to come to work unless seriously ill; 43% had too many patients to see; and 18% didn’t think they were contagious when they headed to work sick. Unfortunately, 15% chose to work while sick because otherwise they would lose pay.

In light of these responses, it’s not surprising that 93% reported they’d seen other medical professionals working when sick.

“My schedule is almost always booked weeks in advance. If someone misses or has to cancel their appointment, they typically have 2-4 weeks to wait to get back in. If I was sick and a full day of patients (or God forbid more than a day) had to be canceled because I called in, it’s so much more work when I return,” says Caitlin Briggs, MD, a psychiatrist in Lexington, Ky.
 

 

 

Doctors’ workplace sick day policy

Most employees’ benefits allow at least a few sick days, but doctors who treat society’s ill patients don’t seem to stay home from work when they’re suffering. So, we asked physicians, official policy aside, whether they thought going to work sick was expected in their workplace. The majority (76%) said yes, while 24% said no.

“Unless I’m dying or extremely contagious, I usually work. At least now, I have the telehealth option. Not saying any of this is right, but it’s the reality we deal with and the choice we must make,” says Dr. Briggs.

Additionally, 58% of polled physicians said their workplace did not have a clearly defined policy against coming to work sick, while 20% said theirs did, and 22% weren’t sure.

“The first thing I heard on the subject as a medical student was that sick people come to the hospital, so if you’re sick, then you come to the hospital too ... to work. If you can’t work, then you will be admitted. Another aphorism was from Churchill, that ‘most of the world’s work is done by people who don’t feel very well,’ ” says Paul Andreason, MD, a psychiatrist in Bethesda, Md.
 

Working in the time of COVID

Working while ill during ordinary times is one thing, but what about working in the time of COVID? Has the pandemic changed the culture of coming to work sick because medical facilities, such as doctor’s offices and hospitals, don’t want their staff coming in when they have COVID?

Surprisingly, when we asked physicians whether the pandemic has made it more or less acceptable to come to work sick, only 61% thought COVID has made it less acceptable to work while sick, while 16% thought it made it more acceptable, and 23% said there’s no change.

“I draw the line at fevers/chills, feeling like you’ve just been run over, or significant enteritis,” says Dr. Abbott. “Also, if I have to take palliative meds that interfere with alertness, I’m not doing my patients any favors.”

While a minority of physicians may call in sick, most still suffer through their sneezing, coughing, chills, and fever while seeing patients as usual.

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

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Before the pandemic, physicians came to work sick, as people do in many other professions. The reasons are likely as varied as, “you weren’t feeling bad enough to miss work,” “you couldn’t afford to miss pay,” “you had too many patients to see,” or “too much work to do.”

In Medscape’s Employed Physicians Report: Loving the Focus, Hating the Bureaucracy, 61% of physicians reported that they sometimes or often come to work sick. Only 2% of respondents said they never come to work unwell.

Medscape wanted to know more about how often you call in sick, how often you come to work feeling unwell, what symptoms you have, and the dogma of your workplace culture regarding sick days. Not to mention the brutal ethos that starts in medical school, in which calling in sick shows weakness or is unacceptable.

So, we polled 2,347 physicians in the United States and abroad and asked them about their sniffling, sneezing, cold, flu, and fever symptoms, and, of course, COVID. Results were split about 50-50 among male and female physicians. The poll ran from Sept. 28 through Oct. 11.
 

Coming to work sick

It’s no surprise that the majority of physicians who were polled (85%) have come to work sick in 2022. In the last prepandemic year (2019), about 70% came to work feeling sick one to five times, and 13% worked while sick six to ten times.

When asked about the symptoms that they’ve previously come to work with, 48% of U.S. physicians said multiple symptoms. They gave high marks for runny nose, cough, congestion, and sore throat. Only 27% have worked with a fever, 22% have worked with other symptoms, and 7% have worked with both strep throat and COVID.

“My workplace, especially in the COVID years, accommodates persons who honestly do not feel well enough to report. Sooner or later, everyone covers for someone else who has to be out,” says Kenneth Abbott, MD, an oncologist in Maryland.
 

The culture of working while sick

Why doctors come to work when they’re sick is complicated. The overwhelming majority of U.S. respondents cited professional obligations; 73% noted that they feel a professional obligation to their patients, and 72% feel a professional obligation to their co-workers. Half of the polled U.S. physicians said they didn’t feel bad enough to stay home, while 48% said they had too much work to do to stay home.

Some 45% said the expectation at their workplace is to come to work unless seriously ill; 43% had too many patients to see; and 18% didn’t think they were contagious when they headed to work sick. Unfortunately, 15% chose to work while sick because otherwise they would lose pay.

In light of these responses, it’s not surprising that 93% reported they’d seen other medical professionals working when sick.

“My schedule is almost always booked weeks in advance. If someone misses or has to cancel their appointment, they typically have 2-4 weeks to wait to get back in. If I was sick and a full day of patients (or God forbid more than a day) had to be canceled because I called in, it’s so much more work when I return,” says Caitlin Briggs, MD, a psychiatrist in Lexington, Ky.
 

 

 

Doctors’ workplace sick day policy

Most employees’ benefits allow at least a few sick days, but doctors who treat society’s ill patients don’t seem to stay home from work when they’re suffering. So, we asked physicians, official policy aside, whether they thought going to work sick was expected in their workplace. The majority (76%) said yes, while 24% said no.

“Unless I’m dying or extremely contagious, I usually work. At least now, I have the telehealth option. Not saying any of this is right, but it’s the reality we deal with and the choice we must make,” says Dr. Briggs.

Additionally, 58% of polled physicians said their workplace did not have a clearly defined policy against coming to work sick, while 20% said theirs did, and 22% weren’t sure.

“The first thing I heard on the subject as a medical student was that sick people come to the hospital, so if you’re sick, then you come to the hospital too ... to work. If you can’t work, then you will be admitted. Another aphorism was from Churchill, that ‘most of the world’s work is done by people who don’t feel very well,’ ” says Paul Andreason, MD, a psychiatrist in Bethesda, Md.
 

Working in the time of COVID

Working while ill during ordinary times is one thing, but what about working in the time of COVID? Has the pandemic changed the culture of coming to work sick because medical facilities, such as doctor’s offices and hospitals, don’t want their staff coming in when they have COVID?

Surprisingly, when we asked physicians whether the pandemic has made it more or less acceptable to come to work sick, only 61% thought COVID has made it less acceptable to work while sick, while 16% thought it made it more acceptable, and 23% said there’s no change.

“I draw the line at fevers/chills, feeling like you’ve just been run over, or significant enteritis,” says Dr. Abbott. “Also, if I have to take palliative meds that interfere with alertness, I’m not doing my patients any favors.”

While a minority of physicians may call in sick, most still suffer through their sneezing, coughing, chills, and fever while seeing patients as usual.

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

Before the pandemic, physicians came to work sick, as people do in many other professions. The reasons are likely as varied as, “you weren’t feeling bad enough to miss work,” “you couldn’t afford to miss pay,” “you had too many patients to see,” or “too much work to do.”

In Medscape’s Employed Physicians Report: Loving the Focus, Hating the Bureaucracy, 61% of physicians reported that they sometimes or often come to work sick. Only 2% of respondents said they never come to work unwell.

Medscape wanted to know more about how often you call in sick, how often you come to work feeling unwell, what symptoms you have, and the dogma of your workplace culture regarding sick days. Not to mention the brutal ethos that starts in medical school, in which calling in sick shows weakness or is unacceptable.

So, we polled 2,347 physicians in the United States and abroad and asked them about their sniffling, sneezing, cold, flu, and fever symptoms, and, of course, COVID. Results were split about 50-50 among male and female physicians. The poll ran from Sept. 28 through Oct. 11.
 

Coming to work sick

It’s no surprise that the majority of physicians who were polled (85%) have come to work sick in 2022. In the last prepandemic year (2019), about 70% came to work feeling sick one to five times, and 13% worked while sick six to ten times.

When asked about the symptoms that they’ve previously come to work with, 48% of U.S. physicians said multiple symptoms. They gave high marks for runny nose, cough, congestion, and sore throat. Only 27% have worked with a fever, 22% have worked with other symptoms, and 7% have worked with both strep throat and COVID.

“My workplace, especially in the COVID years, accommodates persons who honestly do not feel well enough to report. Sooner or later, everyone covers for someone else who has to be out,” says Kenneth Abbott, MD, an oncologist in Maryland.
 

The culture of working while sick

Why doctors come to work when they’re sick is complicated. The overwhelming majority of U.S. respondents cited professional obligations; 73% noted that they feel a professional obligation to their patients, and 72% feel a professional obligation to their co-workers. Half of the polled U.S. physicians said they didn’t feel bad enough to stay home, while 48% said they had too much work to do to stay home.

Some 45% said the expectation at their workplace is to come to work unless seriously ill; 43% had too many patients to see; and 18% didn’t think they were contagious when they headed to work sick. Unfortunately, 15% chose to work while sick because otherwise they would lose pay.

In light of these responses, it’s not surprising that 93% reported they’d seen other medical professionals working when sick.

“My schedule is almost always booked weeks in advance. If someone misses or has to cancel their appointment, they typically have 2-4 weeks to wait to get back in. If I was sick and a full day of patients (or God forbid more than a day) had to be canceled because I called in, it’s so much more work when I return,” says Caitlin Briggs, MD, a psychiatrist in Lexington, Ky.
 

 

 

Doctors’ workplace sick day policy

Most employees’ benefits allow at least a few sick days, but doctors who treat society’s ill patients don’t seem to stay home from work when they’re suffering. So, we asked physicians, official policy aside, whether they thought going to work sick was expected in their workplace. The majority (76%) said yes, while 24% said no.

“Unless I’m dying or extremely contagious, I usually work. At least now, I have the telehealth option. Not saying any of this is right, but it’s the reality we deal with and the choice we must make,” says Dr. Briggs.

Additionally, 58% of polled physicians said their workplace did not have a clearly defined policy against coming to work sick, while 20% said theirs did, and 22% weren’t sure.

“The first thing I heard on the subject as a medical student was that sick people come to the hospital, so if you’re sick, then you come to the hospital too ... to work. If you can’t work, then you will be admitted. Another aphorism was from Churchill, that ‘most of the world’s work is done by people who don’t feel very well,’ ” says Paul Andreason, MD, a psychiatrist in Bethesda, Md.
 

Working in the time of COVID

Working while ill during ordinary times is one thing, but what about working in the time of COVID? Has the pandemic changed the culture of coming to work sick because medical facilities, such as doctor’s offices and hospitals, don’t want their staff coming in when they have COVID?

Surprisingly, when we asked physicians whether the pandemic has made it more or less acceptable to come to work sick, only 61% thought COVID has made it less acceptable to work while sick, while 16% thought it made it more acceptable, and 23% said there’s no change.

“I draw the line at fevers/chills, feeling like you’ve just been run over, or significant enteritis,” says Dr. Abbott. “Also, if I have to take palliative meds that interfere with alertness, I’m not doing my patients any favors.”

While a minority of physicians may call in sick, most still suffer through their sneezing, coughing, chills, and fever while seeing patients as usual.

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

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Stroke risk rises with years of drinking in young adults

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Tue, 11/22/2022 - 11:12

Young adults who are moderate to heavy drinkers are at increased risk of suffering a stroke – and the risk goes up with more years of imbibing, a new study suggests.

“The rate of stroke among young adults has been increasing over the last few decades, and stroke in young adults causes death and serious disability,” study coauthor Eue-Keun Choi, MD, PhD, of Seoul National University, Republic of Korea, said in a statement.

“If we could prevent stroke in young adults by reducing alcohol consumption, that could potentially have a substantial impact on the health of individuals and the overall burden of stroke on society,” Dr. Choi added.

The study was published online in Neurology.

Compounding effects

Using data from a Korean national health database, the researchers identified roughly 1.5 million adults aged 20-39 years (mean age 29.5 years, 72% male) who had four consecutive annual health examinations during which they were asked about their alcohol use.

During a median follow-up of roughly 6 years, 3,153 individuals suffered a stroke.

After multivariate adjustment accounting for other factors that could affect the risk for stroke, such as hypertension, smoking, and body mass index, the risk of stroke increased steadily with the number of years of moderate to heavy drinking, defined as 105 grams or more of alcohol per week.

Compared with light drinkers or teetotalers, stroke risk increased 19% with 2 years of moderate to heavy drinking and 22% and 23%, respectively, for 3 and 4 years of moderate or heaving drinking.

The positive dose-response relationship was chiefly driven by increased risk of hemorrhagic stroke; with 2, 3 and 4 years of moderate to heavy drinking, hemorrhagic stroke risk increased 30%, 42% and 36%, respectively, relative to light/no drinking.

“Since more than 90% of the burden of stroke overall can be attributed to potentially modifiable risk factors, including alcohol consumption, and since stroke in young adults severely impacts both the individual and society by limiting their activities during their most productive years, reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any strategy to prevent stroke,” Dr. Choi said.

A limitation of the study is that only Korean people were included, so the results may not apply to people of other races and ethnicities, they noted. In addition, people filled out questionnaires about their alcohol consumption, which may introduce recall bias.
 

Consistent evidence

“For decades, the evidence was suggestive that a moderate amount of alcohol daily is actually beneficial – one to two drinks in men and one drink in women – at reducing major vascular outcomes,” Pierre Fayad, MD, professor, department of neurological sciences, and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said in commenting on the research.

Yet, over the past few years, some research has found no evidence of benefit with moderate alcohol intake. There is, however, “consistent evidence” that shows a detrimental effect of excessive alcohol, particularly binge drinking, especially in young adults, Dr. Fayad said.

This study, he said, “adds to the known detrimental effects of excessive alcohol intake, in increasing the risk of stroke, particularly in young adults.

“The bottom line: Young adults who usually have a low risk of stroke increase their risk significantly by heavy alcohol drinking, and Koreans are equally at risk as other populations,” Dr. Fayad said.

The study was supported by the Korea Medical Device Development Fund and the Korea National Research Foundation. Dr. Choi and Dr. Fayad report no relevant financial relationships.

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

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Young adults who are moderate to heavy drinkers are at increased risk of suffering a stroke – and the risk goes up with more years of imbibing, a new study suggests.

“The rate of stroke among young adults has been increasing over the last few decades, and stroke in young adults causes death and serious disability,” study coauthor Eue-Keun Choi, MD, PhD, of Seoul National University, Republic of Korea, said in a statement.

“If we could prevent stroke in young adults by reducing alcohol consumption, that could potentially have a substantial impact on the health of individuals and the overall burden of stroke on society,” Dr. Choi added.

The study was published online in Neurology.

Compounding effects

Using data from a Korean national health database, the researchers identified roughly 1.5 million adults aged 20-39 years (mean age 29.5 years, 72% male) who had four consecutive annual health examinations during which they were asked about their alcohol use.

During a median follow-up of roughly 6 years, 3,153 individuals suffered a stroke.

After multivariate adjustment accounting for other factors that could affect the risk for stroke, such as hypertension, smoking, and body mass index, the risk of stroke increased steadily with the number of years of moderate to heavy drinking, defined as 105 grams or more of alcohol per week.

Compared with light drinkers or teetotalers, stroke risk increased 19% with 2 years of moderate to heavy drinking and 22% and 23%, respectively, for 3 and 4 years of moderate or heaving drinking.

The positive dose-response relationship was chiefly driven by increased risk of hemorrhagic stroke; with 2, 3 and 4 years of moderate to heavy drinking, hemorrhagic stroke risk increased 30%, 42% and 36%, respectively, relative to light/no drinking.

“Since more than 90% of the burden of stroke overall can be attributed to potentially modifiable risk factors, including alcohol consumption, and since stroke in young adults severely impacts both the individual and society by limiting their activities during their most productive years, reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any strategy to prevent stroke,” Dr. Choi said.

A limitation of the study is that only Korean people were included, so the results may not apply to people of other races and ethnicities, they noted. In addition, people filled out questionnaires about their alcohol consumption, which may introduce recall bias.
 

Consistent evidence

“For decades, the evidence was suggestive that a moderate amount of alcohol daily is actually beneficial – one to two drinks in men and one drink in women – at reducing major vascular outcomes,” Pierre Fayad, MD, professor, department of neurological sciences, and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said in commenting on the research.

Yet, over the past few years, some research has found no evidence of benefit with moderate alcohol intake. There is, however, “consistent evidence” that shows a detrimental effect of excessive alcohol, particularly binge drinking, especially in young adults, Dr. Fayad said.

This study, he said, “adds to the known detrimental effects of excessive alcohol intake, in increasing the risk of stroke, particularly in young adults.

“The bottom line: Young adults who usually have a low risk of stroke increase their risk significantly by heavy alcohol drinking, and Koreans are equally at risk as other populations,” Dr. Fayad said.

The study was supported by the Korea Medical Device Development Fund and the Korea National Research Foundation. Dr. Choi and Dr. Fayad report no relevant financial relationships.

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

Young adults who are moderate to heavy drinkers are at increased risk of suffering a stroke – and the risk goes up with more years of imbibing, a new study suggests.

“The rate of stroke among young adults has been increasing over the last few decades, and stroke in young adults causes death and serious disability,” study coauthor Eue-Keun Choi, MD, PhD, of Seoul National University, Republic of Korea, said in a statement.

“If we could prevent stroke in young adults by reducing alcohol consumption, that could potentially have a substantial impact on the health of individuals and the overall burden of stroke on society,” Dr. Choi added.

The study was published online in Neurology.

Compounding effects

Using data from a Korean national health database, the researchers identified roughly 1.5 million adults aged 20-39 years (mean age 29.5 years, 72% male) who had four consecutive annual health examinations during which they were asked about their alcohol use.

During a median follow-up of roughly 6 years, 3,153 individuals suffered a stroke.

After multivariate adjustment accounting for other factors that could affect the risk for stroke, such as hypertension, smoking, and body mass index, the risk of stroke increased steadily with the number of years of moderate to heavy drinking, defined as 105 grams or more of alcohol per week.

Compared with light drinkers or teetotalers, stroke risk increased 19% with 2 years of moderate to heavy drinking and 22% and 23%, respectively, for 3 and 4 years of moderate or heaving drinking.

The positive dose-response relationship was chiefly driven by increased risk of hemorrhagic stroke; with 2, 3 and 4 years of moderate to heavy drinking, hemorrhagic stroke risk increased 30%, 42% and 36%, respectively, relative to light/no drinking.

“Since more than 90% of the burden of stroke overall can be attributed to potentially modifiable risk factors, including alcohol consumption, and since stroke in young adults severely impacts both the individual and society by limiting their activities during their most productive years, reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any strategy to prevent stroke,” Dr. Choi said.

A limitation of the study is that only Korean people were included, so the results may not apply to people of other races and ethnicities, they noted. In addition, people filled out questionnaires about their alcohol consumption, which may introduce recall bias.
 

Consistent evidence

“For decades, the evidence was suggestive that a moderate amount of alcohol daily is actually beneficial – one to two drinks in men and one drink in women – at reducing major vascular outcomes,” Pierre Fayad, MD, professor, department of neurological sciences, and director of the Nebraska Stroke Center, University of Nebraska Medical Center, Omaha, said in commenting on the research.

Yet, over the past few years, some research has found no evidence of benefit with moderate alcohol intake. There is, however, “consistent evidence” that shows a detrimental effect of excessive alcohol, particularly binge drinking, especially in young adults, Dr. Fayad said.

This study, he said, “adds to the known detrimental effects of excessive alcohol intake, in increasing the risk of stroke, particularly in young adults.

“The bottom line: Young adults who usually have a low risk of stroke increase their risk significantly by heavy alcohol drinking, and Koreans are equally at risk as other populations,” Dr. Fayad said.

The study was supported by the Korea Medical Device Development Fund and the Korea National Research Foundation. Dr. Choi and Dr. Fayad report no relevant financial relationships.

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

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New CDC guidance on prescribing opioids for pain

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Mon, 11/07/2022 - 08:01

The U.S. Centers for Disease Control and Prevention has released updated and expanded recommendations for prescribing opioids for adults with acute and chronic pain not related to cancer, sickle cell disease, or palliative/end-of-life care.

The 2022 Clinical Practice Guideline provides guidance on determining whether to initiate opioids for pain; selecting opioids and determining opioid dosages; deciding duration of initial opioid prescription and conducting follow-up; and assessing risk and addressing potential harms of opioid use.

“Patients with pain should receive compassionate, safe, and effective pain care. We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life,” Christopher M. Jones, PharmD, DrPH, acting director for the CDC’s National Center for Injury Prevention and Control, said in a news release.
 

How to taper safely

The last guideline on the topic was released by CDC in 2016. Since then, new evidence has emerged regarding the benefits and risks of prescription opioids for acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent effects, risk mitigation strategies, and opioid tapering and discontinuation, the CDC says.

A “critical” addition to the 2022 guideline is advice on tapering opioids, Dr. Jones said during a press briefing.

“Practical tips on how to taper in an individualized patient-centered manner have been added to help clinicians if the decision is made to taper opioids, and the guideline explicitly advises against abrupt discontinuation or rapid dose reductions of opioids,” Dr. Jones said.

“That is based on lessons learned over the last several years as well as new science about how we approach tapering and the real harms that can result when patients are abruptly discontinued or rapidly tapered,” he added.

The updated guideline was published online Nov. 3 in the Morbidity and Mortality Weekly Report.

Key recommendations in the 100-page document include the following:

  • In determining whether or not to initiate opioids, nonopioid therapies are at least as effective as opioids for many common types of acute pain. Use of nondrug and nonopioid drug therapies should be maximized as appropriate, and opioid therapy should only be considered for acute pain if it is anticipated that benefits outweigh risks to the patient.
  • Before starting opioid therapy, providers should discuss with patients the realistic benefits and known risks of opioid therapy.
  • Before starting ongoing opioid therapy for patients with subacute pain lasting 1 to 3 months or chronic pain lasting more than 3 months, providers should work with patients to establish treatment goals for pain and function, and consideration should be given as to how opioid therapy will be discontinued if benefits do not outweigh risks.
  • Once opioids are started, the lowest effective dose of immediate-release opioids should be prescribed for no longer than needed for the expected duration of pain severe enough to require opioids.
  • Within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain, providers should work with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy; care should be exercised when increasing, continuing, or reducing opioid dosage.
  • Before starting and periodically during ongoing opioid therapy, providers should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substance used.
  • Abrupt discontinuation of opioids should be avoided, especially for patients receiving high doses.
  • For treating patients with opioid use disorder, treatment with evidence-based medications should be provided, or arrangements for such treatment should be made.

Dr. Jones emphasized that the guideline is “voluntary and meant to guide shared decision-making between a clinician and patient. It’s not meant to be implemented as absolute limits of policy or practice by clinicians, health systems, insurance companies, governmental entities.”

He also noted that the “current state of the overdose crisis, which is very much driven by illicit synthetic opioids, is not the aim of this guideline.

“The release of this guideline is really about advancing pain care and improving the lives of patients living with pain,” he said.

“We know that at least 1 in 5 people in the country have chronic pain. It’s one of the most common reasons why people present to their health care provider, and the goal here is to advance pain care, function, and quality of life for that patient population, while also reducing misuse, diversion, and consequences of prescription opioid misuse,” Dr. Jones added.

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

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The U.S. Centers for Disease Control and Prevention has released updated and expanded recommendations for prescribing opioids for adults with acute and chronic pain not related to cancer, sickle cell disease, or palliative/end-of-life care.

The 2022 Clinical Practice Guideline provides guidance on determining whether to initiate opioids for pain; selecting opioids and determining opioid dosages; deciding duration of initial opioid prescription and conducting follow-up; and assessing risk and addressing potential harms of opioid use.

“Patients with pain should receive compassionate, safe, and effective pain care. We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life,” Christopher M. Jones, PharmD, DrPH, acting director for the CDC’s National Center for Injury Prevention and Control, said in a news release.
 

How to taper safely

The last guideline on the topic was released by CDC in 2016. Since then, new evidence has emerged regarding the benefits and risks of prescription opioids for acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent effects, risk mitigation strategies, and opioid tapering and discontinuation, the CDC says.

A “critical” addition to the 2022 guideline is advice on tapering opioids, Dr. Jones said during a press briefing.

“Practical tips on how to taper in an individualized patient-centered manner have been added to help clinicians if the decision is made to taper opioids, and the guideline explicitly advises against abrupt discontinuation or rapid dose reductions of opioids,” Dr. Jones said.

“That is based on lessons learned over the last several years as well as new science about how we approach tapering and the real harms that can result when patients are abruptly discontinued or rapidly tapered,” he added.

The updated guideline was published online Nov. 3 in the Morbidity and Mortality Weekly Report.

Key recommendations in the 100-page document include the following:

  • In determining whether or not to initiate opioids, nonopioid therapies are at least as effective as opioids for many common types of acute pain. Use of nondrug and nonopioid drug therapies should be maximized as appropriate, and opioid therapy should only be considered for acute pain if it is anticipated that benefits outweigh risks to the patient.
  • Before starting opioid therapy, providers should discuss with patients the realistic benefits and known risks of opioid therapy.
  • Before starting ongoing opioid therapy for patients with subacute pain lasting 1 to 3 months or chronic pain lasting more than 3 months, providers should work with patients to establish treatment goals for pain and function, and consideration should be given as to how opioid therapy will be discontinued if benefits do not outweigh risks.
  • Once opioids are started, the lowest effective dose of immediate-release opioids should be prescribed for no longer than needed for the expected duration of pain severe enough to require opioids.
  • Within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain, providers should work with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy; care should be exercised when increasing, continuing, or reducing opioid dosage.
  • Before starting and periodically during ongoing opioid therapy, providers should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substance used.
  • Abrupt discontinuation of opioids should be avoided, especially for patients receiving high doses.
  • For treating patients with opioid use disorder, treatment with evidence-based medications should be provided, or arrangements for such treatment should be made.

Dr. Jones emphasized that the guideline is “voluntary and meant to guide shared decision-making between a clinician and patient. It’s not meant to be implemented as absolute limits of policy or practice by clinicians, health systems, insurance companies, governmental entities.”

He also noted that the “current state of the overdose crisis, which is very much driven by illicit synthetic opioids, is not the aim of this guideline.

“The release of this guideline is really about advancing pain care and improving the lives of patients living with pain,” he said.

“We know that at least 1 in 5 people in the country have chronic pain. It’s one of the most common reasons why people present to their health care provider, and the goal here is to advance pain care, function, and quality of life for that patient population, while also reducing misuse, diversion, and consequences of prescription opioid misuse,” Dr. Jones added.

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

The U.S. Centers for Disease Control and Prevention has released updated and expanded recommendations for prescribing opioids for adults with acute and chronic pain not related to cancer, sickle cell disease, or palliative/end-of-life care.

The 2022 Clinical Practice Guideline provides guidance on determining whether to initiate opioids for pain; selecting opioids and determining opioid dosages; deciding duration of initial opioid prescription and conducting follow-up; and assessing risk and addressing potential harms of opioid use.

“Patients with pain should receive compassionate, safe, and effective pain care. We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life,” Christopher M. Jones, PharmD, DrPH, acting director for the CDC’s National Center for Injury Prevention and Control, said in a news release.
 

How to taper safely

The last guideline on the topic was released by CDC in 2016. Since then, new evidence has emerged regarding the benefits and risks of prescription opioids for acute and chronic pain, comparisons with nonopioid pain treatments, dosing strategies, opioid dose-dependent effects, risk mitigation strategies, and opioid tapering and discontinuation, the CDC says.

A “critical” addition to the 2022 guideline is advice on tapering opioids, Dr. Jones said during a press briefing.

“Practical tips on how to taper in an individualized patient-centered manner have been added to help clinicians if the decision is made to taper opioids, and the guideline explicitly advises against abrupt discontinuation or rapid dose reductions of opioids,” Dr. Jones said.

“That is based on lessons learned over the last several years as well as new science about how we approach tapering and the real harms that can result when patients are abruptly discontinued or rapidly tapered,” he added.

The updated guideline was published online Nov. 3 in the Morbidity and Mortality Weekly Report.

Key recommendations in the 100-page document include the following:

  • In determining whether or not to initiate opioids, nonopioid therapies are at least as effective as opioids for many common types of acute pain. Use of nondrug and nonopioid drug therapies should be maximized as appropriate, and opioid therapy should only be considered for acute pain if it is anticipated that benefits outweigh risks to the patient.
  • Before starting opioid therapy, providers should discuss with patients the realistic benefits and known risks of opioid therapy.
  • Before starting ongoing opioid therapy for patients with subacute pain lasting 1 to 3 months or chronic pain lasting more than 3 months, providers should work with patients to establish treatment goals for pain and function, and consideration should be given as to how opioid therapy will be discontinued if benefits do not outweigh risks.
  • Once opioids are started, the lowest effective dose of immediate-release opioids should be prescribed for no longer than needed for the expected duration of pain severe enough to require opioids.
  • Within 1 to 4 weeks of starting opioid therapy for subacute or chronic pain, providers should work with patients to evaluate and carefully weigh benefits and risks of continuing opioid therapy; care should be exercised when increasing, continuing, or reducing opioid dosage.
  • Before starting and periodically during ongoing opioid therapy, providers should evaluate risk for opioid-related harms and should work with patients to incorporate relevant strategies to mitigate risk, including offering naloxone and reviewing potential interactions with any other prescribed medications or substance used.
  • Abrupt discontinuation of opioids should be avoided, especially for patients receiving high doses.
  • For treating patients with opioid use disorder, treatment with evidence-based medications should be provided, or arrangements for such treatment should be made.

Dr. Jones emphasized that the guideline is “voluntary and meant to guide shared decision-making between a clinician and patient. It’s not meant to be implemented as absolute limits of policy or practice by clinicians, health systems, insurance companies, governmental entities.”

He also noted that the “current state of the overdose crisis, which is very much driven by illicit synthetic opioids, is not the aim of this guideline.

“The release of this guideline is really about advancing pain care and improving the lives of patients living with pain,” he said.

“We know that at least 1 in 5 people in the country have chronic pain. It’s one of the most common reasons why people present to their health care provider, and the goal here is to advance pain care, function, and quality of life for that patient population, while also reducing misuse, diversion, and consequences of prescription opioid misuse,” Dr. Jones added.

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

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Sexual activities in seniors: Experts advise on what to ask

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Mon, 11/07/2022 - 10:31

Sexual activity in older adults is something of a taboo, rarely discussed and largely ignored by researchers.

But failing to address human sexuality in old age can lead doctors to ask seniors the wrong questions about sex – if they ask at all.

When researchers do look at the issue, they find surprises, as Janie Steckenrider, PhD, has learned. In a new study presented at the annual scientific meeting of the Gerontological Society of America, Dr. Steckenrider, a professor of political science at Loyola Marymount University, Los Angeles, found that previous attempts to qualify the sexual activities of seniors appear to be limited largely to partnered sex – despite the fact that many older people tend to practice “solo sex,” another term for masturbation.

“Maybe they don’t have a partner, or their partner has sexual dysfunction, or has died. There could be pain involved,” Dr. Steckenrider said. “In the hierarchy of sexual activity, penetrative sex is the cultural norm. As people get older, penetrative sex becomes less important. The hierarchy shifts to include more emotional intimacy like touching and fondling.”

Of the 17 survey questionnaires Dr. Steckenrider analyzed, 11 had questions that focused exclusively on sex with a partner. Nine defined sexual activity and just five included questions about masturbation.

Take, for example, a 2018 poll by researchers at the University of Michigan, Ann Arbor, who found that 40% of people ages 65-80 said they were sexually active. Meanwhile, nearly two thirds of older adults said they were interested in sex, and more than half said sex was important to their quality of life.

But Dr. Steckenrider said this poll, like others, left the term “sexually active” undefined – raising questions about the meaning of the findings.

Sheryl A. Kingsberg, PhD, chief of behavioral medicine in the department of obstetrics and gynecology at University Hospitals Cleveland Medical Center, said she was surprised so few of the studies analyzed by Dr. Steckenrider included masturbation in their definition of sex. 

“Clinical trials of potential treatments for female sexual problems, like hypoactive sexual desire disorder or painful sex, include both definitions of sexual activity and questions about masturbation, she said. “Definitions also should not assume partnered sex is male or female,” she added. 

Dr. Steckenrider and Dr. Kingsberg encouraged healthcare providers to address the sexual health of their patients by asking questions about their sexual health and concerns. 

“Health care professionals cannot address sexual concerns if they don’t acknowledge their patients as sexual beings and inquire about sexual problems,” Dr. Kingsberg said.

The key, according to Dr. Steckenrider, is for clinicians to ask the right questions. But which ones?  

Detail is crucial. 

“I think that’s far better than asking whether they are sexually active, yes or no,” she said. “Ask: ‘How often have you engaged in these types of sexual activities?’ If you are looking for frequency, and be specific about the types of sex: kissing, fondling, or masturbation.”

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

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Sexual activity in older adults is something of a taboo, rarely discussed and largely ignored by researchers.

But failing to address human sexuality in old age can lead doctors to ask seniors the wrong questions about sex – if they ask at all.

When researchers do look at the issue, they find surprises, as Janie Steckenrider, PhD, has learned. In a new study presented at the annual scientific meeting of the Gerontological Society of America, Dr. Steckenrider, a professor of political science at Loyola Marymount University, Los Angeles, found that previous attempts to qualify the sexual activities of seniors appear to be limited largely to partnered sex – despite the fact that many older people tend to practice “solo sex,” another term for masturbation.

“Maybe they don’t have a partner, or their partner has sexual dysfunction, or has died. There could be pain involved,” Dr. Steckenrider said. “In the hierarchy of sexual activity, penetrative sex is the cultural norm. As people get older, penetrative sex becomes less important. The hierarchy shifts to include more emotional intimacy like touching and fondling.”

Of the 17 survey questionnaires Dr. Steckenrider analyzed, 11 had questions that focused exclusively on sex with a partner. Nine defined sexual activity and just five included questions about masturbation.

Take, for example, a 2018 poll by researchers at the University of Michigan, Ann Arbor, who found that 40% of people ages 65-80 said they were sexually active. Meanwhile, nearly two thirds of older adults said they were interested in sex, and more than half said sex was important to their quality of life.

But Dr. Steckenrider said this poll, like others, left the term “sexually active” undefined – raising questions about the meaning of the findings.

Sheryl A. Kingsberg, PhD, chief of behavioral medicine in the department of obstetrics and gynecology at University Hospitals Cleveland Medical Center, said she was surprised so few of the studies analyzed by Dr. Steckenrider included masturbation in their definition of sex. 

“Clinical trials of potential treatments for female sexual problems, like hypoactive sexual desire disorder or painful sex, include both definitions of sexual activity and questions about masturbation, she said. “Definitions also should not assume partnered sex is male or female,” she added. 

Dr. Steckenrider and Dr. Kingsberg encouraged healthcare providers to address the sexual health of their patients by asking questions about their sexual health and concerns. 

“Health care professionals cannot address sexual concerns if they don’t acknowledge their patients as sexual beings and inquire about sexual problems,” Dr. Kingsberg said.

The key, according to Dr. Steckenrider, is for clinicians to ask the right questions. But which ones?  

Detail is crucial. 

“I think that’s far better than asking whether they are sexually active, yes or no,” she said. “Ask: ‘How often have you engaged in these types of sexual activities?’ If you are looking for frequency, and be specific about the types of sex: kissing, fondling, or masturbation.”

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

Sexual activity in older adults is something of a taboo, rarely discussed and largely ignored by researchers.

But failing to address human sexuality in old age can lead doctors to ask seniors the wrong questions about sex – if they ask at all.

When researchers do look at the issue, they find surprises, as Janie Steckenrider, PhD, has learned. In a new study presented at the annual scientific meeting of the Gerontological Society of America, Dr. Steckenrider, a professor of political science at Loyola Marymount University, Los Angeles, found that previous attempts to qualify the sexual activities of seniors appear to be limited largely to partnered sex – despite the fact that many older people tend to practice “solo sex,” another term for masturbation.

“Maybe they don’t have a partner, or their partner has sexual dysfunction, or has died. There could be pain involved,” Dr. Steckenrider said. “In the hierarchy of sexual activity, penetrative sex is the cultural norm. As people get older, penetrative sex becomes less important. The hierarchy shifts to include more emotional intimacy like touching and fondling.”

Of the 17 survey questionnaires Dr. Steckenrider analyzed, 11 had questions that focused exclusively on sex with a partner. Nine defined sexual activity and just five included questions about masturbation.

Take, for example, a 2018 poll by researchers at the University of Michigan, Ann Arbor, who found that 40% of people ages 65-80 said they were sexually active. Meanwhile, nearly two thirds of older adults said they were interested in sex, and more than half said sex was important to their quality of life.

But Dr. Steckenrider said this poll, like others, left the term “sexually active” undefined – raising questions about the meaning of the findings.

Sheryl A. Kingsberg, PhD, chief of behavioral medicine in the department of obstetrics and gynecology at University Hospitals Cleveland Medical Center, said she was surprised so few of the studies analyzed by Dr. Steckenrider included masturbation in their definition of sex. 

“Clinical trials of potential treatments for female sexual problems, like hypoactive sexual desire disorder or painful sex, include both definitions of sexual activity and questions about masturbation, she said. “Definitions also should not assume partnered sex is male or female,” she added. 

Dr. Steckenrider and Dr. Kingsberg encouraged healthcare providers to address the sexual health of their patients by asking questions about their sexual health and concerns. 

“Health care professionals cannot address sexual concerns if they don’t acknowledge their patients as sexual beings and inquire about sexual problems,” Dr. Kingsberg said.

The key, according to Dr. Steckenrider, is for clinicians to ask the right questions. But which ones?  

Detail is crucial. 

“I think that’s far better than asking whether they are sexually active, yes or no,” she said. “Ask: ‘How often have you engaged in these types of sexual activities?’ If you are looking for frequency, and be specific about the types of sex: kissing, fondling, or masturbation.”

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

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New research confirms recommendations on COVID-19 boosters in MS

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Fri, 11/04/2022 - 12:55

New research confirms the importance of COVID-19 mRNA booster doses for patients with multiple sclerosis (MS) who are receiving the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus), as currently recommended.

“We have shown that even MS patients whose B cells were depleted from circulation with ocrelizumab can mount immune responses to COVID-19 vaccines,” said lead study author Ilya Kister, MD, of NYU Langone’s Multiple Sclerosis Comprehensive Care Center in New York.

The findings were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

VIOLA study

The data stem from VIOLA, an ongoing prospective study of humoral and cellular immune responses to COVID-19 vaccines in 60 patients with MS receiving ocrelizumab at MS care centers at NYU Langone and the University of Colorado Denver.

The mean age of participants was 38 years, 73% were women, all had been taking ocrelizumab for a mean of 1.7 years, and 45% had had COVID-19 prior to vaccination.

The researchers examined antibody and cellular responses to the two-dose series of mRNA COVID-19 vaccine (80% received the Pfizer-BioNTech vaccine, 18% the Moderna vaccine, and 2% unknown) over 24 weeks. In addition, 57% of the participants received the third dose/booster.

Results showed that antibody and cellular responses to SARS-CoV-2 spike protein significantly increased after the two-dose mRNA COVID-19 vaccination, though antibody responses tended to peak between 4 and 12 weeks and declined thereafter. There was no significant decline in cellular responses at week 24.

“The third dose ‘booster’ again significantly increased antibody and cellular responses compared with the pre–third dose levels,” Dr. Kister said.

“Importantly, cellular responses remained elevated or even increased from 4 weeks to 12 weeks after third dose/booster. Overall, these data strongly support the need for a third dose in MS patients on ocrelizumab,” Dr. Kister added.

Participants with “hybrid immunity” (those who had been infected with SARS-CoV-2 and who had also been vaccinated for COVID) had markedly higher SARS-CoV-2–specific antibody and cellular responses than those of peers with vaccine-only immunity.
 

CDC recs

Looking ahead, Dr. Kister said the VIOLA investigators plan to present data on the durability of COVID-19 vaccines in ocrelizumab-treated patients up to 48 weeks after the third dose.

For immunocompromised patients, such as those taking ocrelizumab, the Centers for Disease Control and Prevention considers the third dose of mRNA vaccine not as a “booster” but as part of the regular vaccine series.

“In other words, all these patients should receive three doses as part of their ‘primary’ series,” Dr. Kister noted.

The CDC also recommends receiving the updated booster for COVID-19 that became available in September 2022 (the fourth dose of the vaccine).

“Our study did not evaluate the efficacy of this fourth dose; but based on our results, it is reasonable to suppose that the fourth dose would also lead to a further increase in immune defenses,” Dr. Kister said.

The VIOLA study is an investigator-initiated collaboration supported by F. Hoffmann-La Roche Ltd/Genentech Inc. Dr. Kister has reported no relevant financial relationships.

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

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New research confirms the importance of COVID-19 mRNA booster doses for patients with multiple sclerosis (MS) who are receiving the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus), as currently recommended.

“We have shown that even MS patients whose B cells were depleted from circulation with ocrelizumab can mount immune responses to COVID-19 vaccines,” said lead study author Ilya Kister, MD, of NYU Langone’s Multiple Sclerosis Comprehensive Care Center in New York.

The findings were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

VIOLA study

The data stem from VIOLA, an ongoing prospective study of humoral and cellular immune responses to COVID-19 vaccines in 60 patients with MS receiving ocrelizumab at MS care centers at NYU Langone and the University of Colorado Denver.

The mean age of participants was 38 years, 73% were women, all had been taking ocrelizumab for a mean of 1.7 years, and 45% had had COVID-19 prior to vaccination.

The researchers examined antibody and cellular responses to the two-dose series of mRNA COVID-19 vaccine (80% received the Pfizer-BioNTech vaccine, 18% the Moderna vaccine, and 2% unknown) over 24 weeks. In addition, 57% of the participants received the third dose/booster.

Results showed that antibody and cellular responses to SARS-CoV-2 spike protein significantly increased after the two-dose mRNA COVID-19 vaccination, though antibody responses tended to peak between 4 and 12 weeks and declined thereafter. There was no significant decline in cellular responses at week 24.

“The third dose ‘booster’ again significantly increased antibody and cellular responses compared with the pre–third dose levels,” Dr. Kister said.

“Importantly, cellular responses remained elevated or even increased from 4 weeks to 12 weeks after third dose/booster. Overall, these data strongly support the need for a third dose in MS patients on ocrelizumab,” Dr. Kister added.

Participants with “hybrid immunity” (those who had been infected with SARS-CoV-2 and who had also been vaccinated for COVID) had markedly higher SARS-CoV-2–specific antibody and cellular responses than those of peers with vaccine-only immunity.
 

CDC recs

Looking ahead, Dr. Kister said the VIOLA investigators plan to present data on the durability of COVID-19 vaccines in ocrelizumab-treated patients up to 48 weeks after the third dose.

For immunocompromised patients, such as those taking ocrelizumab, the Centers for Disease Control and Prevention considers the third dose of mRNA vaccine not as a “booster” but as part of the regular vaccine series.

“In other words, all these patients should receive three doses as part of their ‘primary’ series,” Dr. Kister noted.

The CDC also recommends receiving the updated booster for COVID-19 that became available in September 2022 (the fourth dose of the vaccine).

“Our study did not evaluate the efficacy of this fourth dose; but based on our results, it is reasonable to suppose that the fourth dose would also lead to a further increase in immune defenses,” Dr. Kister said.

The VIOLA study is an investigator-initiated collaboration supported by F. Hoffmann-La Roche Ltd/Genentech Inc. Dr. Kister has reported no relevant financial relationships.

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

New research confirms the importance of COVID-19 mRNA booster doses for patients with multiple sclerosis (MS) who are receiving the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus), as currently recommended.

“We have shown that even MS patients whose B cells were depleted from circulation with ocrelizumab can mount immune responses to COVID-19 vaccines,” said lead study author Ilya Kister, MD, of NYU Langone’s Multiple Sclerosis Comprehensive Care Center in New York.

The findings were presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
 

VIOLA study

The data stem from VIOLA, an ongoing prospective study of humoral and cellular immune responses to COVID-19 vaccines in 60 patients with MS receiving ocrelizumab at MS care centers at NYU Langone and the University of Colorado Denver.

The mean age of participants was 38 years, 73% were women, all had been taking ocrelizumab for a mean of 1.7 years, and 45% had had COVID-19 prior to vaccination.

The researchers examined antibody and cellular responses to the two-dose series of mRNA COVID-19 vaccine (80% received the Pfizer-BioNTech vaccine, 18% the Moderna vaccine, and 2% unknown) over 24 weeks. In addition, 57% of the participants received the third dose/booster.

Results showed that antibody and cellular responses to SARS-CoV-2 spike protein significantly increased after the two-dose mRNA COVID-19 vaccination, though antibody responses tended to peak between 4 and 12 weeks and declined thereafter. There was no significant decline in cellular responses at week 24.

“The third dose ‘booster’ again significantly increased antibody and cellular responses compared with the pre–third dose levels,” Dr. Kister said.

“Importantly, cellular responses remained elevated or even increased from 4 weeks to 12 weeks after third dose/booster. Overall, these data strongly support the need for a third dose in MS patients on ocrelizumab,” Dr. Kister added.

Participants with “hybrid immunity” (those who had been infected with SARS-CoV-2 and who had also been vaccinated for COVID) had markedly higher SARS-CoV-2–specific antibody and cellular responses than those of peers with vaccine-only immunity.
 

CDC recs

Looking ahead, Dr. Kister said the VIOLA investigators plan to present data on the durability of COVID-19 vaccines in ocrelizumab-treated patients up to 48 weeks after the third dose.

For immunocompromised patients, such as those taking ocrelizumab, the Centers for Disease Control and Prevention considers the third dose of mRNA vaccine not as a “booster” but as part of the regular vaccine series.

“In other words, all these patients should receive three doses as part of their ‘primary’ series,” Dr. Kister noted.

The CDC also recommends receiving the updated booster for COVID-19 that became available in September 2022 (the fourth dose of the vaccine).

“Our study did not evaluate the efficacy of this fourth dose; but based on our results, it is reasonable to suppose that the fourth dose would also lead to a further increase in immune defenses,” Dr. Kister said.

The VIOLA study is an investigator-initiated collaboration supported by F. Hoffmann-La Roche Ltd/Genentech Inc. Dr. Kister has reported no relevant financial relationships.

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

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Testosterone ranges for young men could help classify deficiency

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Fri, 11/04/2022 - 12:55

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

 

 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

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Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

 

 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

Normative ranges of testosterone in young men have been identified on the basis of a nationally representative data in a new study, and these data are expected to provide guidance when evaluating younger individuals presenting with signs and symptoms of potential testosterone deficiency, according to the investigators.

It has long been known that the ranges of normal testosterone differ by age, but the authors of this study contend that this is the first large-scale, population-based analysis conducted in the United States of testosterone levels among in men aged 20-44 years.

“These findings will provide valuable information that clinicians can use in the evaluation and management of young men presenting with concerns about testosterone deficiency,” reported a team of investigators led by Alex Zhu, MD, a urology resident at the University of Michigan, Ann Arbor, in the Journal of Urology.

Outside experts, however, disagree, one saying that the conclusions are “far off and irrational.”

A normative range of testosterone is particularly important for the evaluation of hypogonadism because values vary markedly between individuals and within individuals on repeat measurements over a 24-hour period. At least partially because of this variability, many guidelines, including those issued in by the Endocrine Society and the American Urological Association, recommend testosterone assays only in symptomatic individuals in order to reduce risk of detecting low relative levels that are not clinically relevant.
 

NHANES data provide norms

The data for this study were drawn from the National Health and Nutrition Examination Surveys (NHANES), which sample representative United States residents. The analytic cohort included 1,486 men stratified in 5-year age intervals (20-24, 25-29, 30-34, 35-39, and 40-44).

Because of the known diurnal variation in endocrine levels, only morning total testosterone levels were considered, for consistency. Individuals at risk of disturbed testosterone levels, such as those on hormonal therapy or with a history of testicular cancer, were excluded. Unlike previous analyses that have limited measurements to nonobese individuals without major comorbidities, no such restrictions were imposed in this analysis, which included a sample balanced by race.

After dividing the testosterone levels collected in the NHANES data by tertiles, the cutoff for reduced testosterone were defined as the lowest tertile for each of the five age groups studied.

Consistent with previous reports that testosterone levels decline with age, the cutoff for low testosterone declined for each increase in 5-year age interval after the age of 29 years.

Specifically, these cutoffs were, in order of advancing age, 409 ng/dL (middle tertile range, 409-558), 413 ng/dL (range, 413-575), 359 ng/dL (range, 359-498), 352 ng/dL (range, 352-478), and 350 ng/dL (range, 350-473).

As in the AUA guidelines, which define a total testosterone level below 300 ng/dL “as a reasonable cutoff in support of the diagnosis of low testosterone,” these cutoffs were established without correlation with symptoms. In younger men, like older men, testosterone levels must be within a clinical context.

“Per the AUA guidelines, clinician should consider measuring testosterone levels in patients with certain medical conditions or signs or symptoms of testosterone deficiency, such as depression, reduced motivation, infertility, reduced sex drive, and changes in erectile function,” Dr. Zhu said in an interview, adding that it is appropriate to follow the AUA guidelines “regardless of age.”
 

 

 

Hormone levels and symptoms not correlated

These recommendations are based on the fact that the correlation between symptomatic hypogonadism and testosterone levels is poor, meaning that other factors should be considered when considering whether symptoms relate to deficiency. However, Dr. Zhu contended that objective evidence of a low level of testosterone is useful in considering the role of hormone deficiency.

“Even if one were to choose a different cutoff, our age-specific normative testosterone ranges still provide young men and their physicians a framework for counseling,” according to Dr. Zhu. Because of the risk of nonspecific symptoms, such as fatigue and diminished physical performance, he called for “a high index of suspicion for testosterone deficiency even when evaluating younger men.”

Considering the diurnal fluctuations, the single measurement employed to calculate normative ranges is a limitation of this study, the authors acknowledged. They cited data suggested that up to 35% of men classified as hypogonadal on the basis of a single testosterone assay will not meet the same criterion even if evaluated in the subsequent 24 hours. It is for this reason that guidelines typically recommend measuring testosterone at least twice or with more than one type of assay.

Up until now, decisions about testosterone deficiency have been with a one-size-fits-all approach, but it has long been known that patient age is a variable in determining average levels of this hormone, Dr. Zhu reported. For this reason, he predicted that these data will have clinical utility.

“We believe that our new cutoffs play an important role in evaluating younger men presenting with symptoms [of testosterone deficiency],” Dr. Zhu said. “However, clinicians should still remember that these symptoms have causes other than low testosterone, so we cannot only focus only on testing testosterone.”

However, given the lack of correlation between symptoms and testosterone levels, this area remains controversial.
 

Value of tertile cutoffs questioned

Two independent experts challenged the methodology and conclusions of this study.

Victor Adlin, MD, an associate professor emeritus at Temple University, Philadelphia, questioned tertile levels as an approach to defining normal.

“The authors propose unusually high cut-points for a definition of low testosterone in young men,” said Dr. Adlin, whose published a comment on age-related low testosterone in response to 2020 guidelines issued by the American College of Physicians. He is concerned that these data could lead to overtreatment.

The authors “imply that [these data] would justify treatment with testosterone in many young men with symptoms such as fatigue, depression, and lack of vigor, whose relation to low testosterone is controversial,” he said in an interview. “Trials in older men have failed to show a clear response of such symptoms to testosterone therapy.”

The first author of the 2018 Endocrine Society guidelines, Shalender Bhasin, MB, BS, director of a research program in aging and metabolism at the Brigham and Women’s Hospital in Boston, was even more skeptical.

“The whole premise of generating cutoffs for a disease or condition based on the middle tertile is just so far off and irrational,” he said. A coauthor of a 2017 study designed to define harmonized testosterone reference ranges by decade of age (that he described as providing “a much larger sample size and a wider age range” than this current study), Dr. Bhasin did not see any value in the NHANES-based analysis.

Rather, he called for an effort “to dispel this ill-conceived idea that could mislead young men to think they need testosterone treatment when they are healthy.”

Dr. Zhu and Dr. Adlin reported no potential conflicts of interest. Dr. Bhasin reported financial relationships with AbbVie, Eli Lilly, Novartis, Regeneron, and Takeda.
 

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