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Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis
Scott Worswick, MD
Dr. Worswick provided us with a helpful discussion of the differential diagnosis for erythema multiforme (EM) and Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) and a review of the current literature on treatment options.
He first led us through a detailed differential diagnosis of various conditions that can cause mucosal erosions, targets or targetoid lesions, or dusky erythema and skin pain. Six patient cases were presented, which included interesting presentations of cytomegalovirus infection, a hot water burn injury, paraneoplastic pemphigus, SJS-TEN overlap, Chikungunya virus infection, and linear IgA bullous disease.
Mild self-limited EM can be treated with topical steroids and magic mouthwash. Prophylaxis for oral acyclovir 400mg twice daily has been shown to decrease recurrent attacks of EM in patients with HSV as a trigger. Oral levamisole 150mg daily for 3 days and systemic steroids are helpful treatments for EM flares, although levamisole is not currently available for human use in the U.S. Other treatments for persistent or recurrent EM control include dapsone, thalidomide, apremilast, adalimumab, mycophenolate, and rituximab. Of these, Dr. Worswick has found thalidomide to be the most effective.
In several studies, cyclosporine was found to have an improved mortality benefit in treatment of SJS/TEN. However, cyclosporine is generally not used in patients with renal dysfunction or on dialysis, so the mortality benefit may be skewed. Lower mortality was also seen in treatment with etanercept and IVIG with steroids, but not with steroid monotherapy, IVIG monotherapy, or supportive care alone. In Dr. Worswick’s experiences at UCLA and USC, as well as several published studies, treatment with etanercept was associated with arrest of progression, increased rate of re-epithelialization, and decreased mortality. No significant complications or side effects were seen with treatment. One study to look out for is an upcoming phase III randomized clinical trial comparing supportive care, cyclosporine, and etanercept for SJS/TEN.
He first led us through a detailed differential diagnosis of various conditions that can cause mucosal erosions, targets or targetoid lesions, or dusky erythema and skin pain. Six patient cases were presented, which included interesting presentations of cytomegalovirus infection, a hot water burn injury, paraneoplastic pemphigus, SJS-TEN overlap, Chikungunya virus infection, and linear IgA bullous disease.
Mild self-limited EM can be treated with topical steroids and magic mouthwash. Prophylaxis for oral acyclovir 400mg twice daily has been shown to decrease recurrent attacks of EM in patients with HSV as a trigger. Oral levamisole 150mg daily for 3 days and systemic steroids are helpful treatments for EM flares, although levamisole is not currently available for human use in the U.S. Other treatments for persistent or recurrent EM control include dapsone, thalidomide, apremilast, adalimumab, mycophenolate, and rituximab. Of these, Dr. Worswick has found thalidomide to be the most effective.
In several studies, cyclosporine was found to have an improved mortality benefit in treatment of SJS/TEN. However, cyclosporine is generally not used in patients with renal dysfunction or on dialysis, so the mortality benefit may be skewed. Lower mortality was also seen in treatment with etanercept and IVIG with steroids, but not with steroid monotherapy, IVIG monotherapy, or supportive care alone. In Dr. Worswick’s experiences at UCLA and USC, as well as several published studies, treatment with etanercept was associated with arrest of progression, increased rate of re-epithelialization, and decreased mortality. No significant complications or side effects were seen with treatment. One study to look out for is an upcoming phase III randomized clinical trial comparing supportive care, cyclosporine, and etanercept for SJS/TEN.
Hidradenitis Suppurativa
Jennifer Hsiao, MD
Dr. Hsiao provided us with a wonderful review of hidradenitis suppurativa (HS) and her expert tips for management of this disease. The pathogenesis of HS is complex and involves immune dysregulation, hormones, follicular occlusion, genetics, the microbiome, metabolic dysfunction, and local friction or irritation.
Topical treatments include antibiotics and antiseptic washes, as well as resorcinol which may reduce pain and size of lesions. For Hurley Stage I or II patients, antibiotic monotherapy with doxycycline or dapsone may be effective. Combination regimens to consider are clindamycin and rifampin, or rifampin and moxifloxacin/levofloxacin and metronidazole. Severe HS patients may be treated with induction therapy of IV ertapenem for 6 weeks prior to consolidation treatment with oral antibiotics.
Oral retinoids such as acitretin may be beneficial, although the results for isotretinoin in the literature are mixed. Apremilast is another oral medication that may be beneficial in mild to moderate HS. Hormonal therapy includes spironolactone, oral contraceptives, finasteride, and metformin.
Adalimumab and infliximab are the biologics with the most evidence, although other biologics may be considered such as secukinumab, ustekinumab, anakinra, or IL-23 inhibitors. Isoniazid, etanercept, and intravenous immunoglobulin (IVIG) are therapies not currently supported by the literature.
Procedural management of HS includes intralesional steroid injections, botulinum toxin, laser therapy including laser hair removal, and wide local excision.
When treating a patient with HS, we should consider their medical comorbidities and complications of the disease. For patients with recalcitrant disease or who are not good surgical candidates, combination therapies and a multidisciplinary approach may be helpful.
Topical treatments include antibiotics and antiseptic washes, as well as resorcinol which may reduce pain and size of lesions. For Hurley Stage I or II patients, antibiotic monotherapy with doxycycline or dapsone may be effective. Combination regimens to consider are clindamycin and rifampin, or rifampin and moxifloxacin/levofloxacin and metronidazole. Severe HS patients may be treated with induction therapy of IV ertapenem for 6 weeks prior to consolidation treatment with oral antibiotics.
Oral retinoids such as acitretin may be beneficial, although the results for isotretinoin in the literature are mixed. Apremilast is another oral medication that may be beneficial in mild to moderate HS. Hormonal therapy includes spironolactone, oral contraceptives, finasteride, and metformin.
Adalimumab and infliximab are the biologics with the most evidence, although other biologics may be considered such as secukinumab, ustekinumab, anakinra, or IL-23 inhibitors. Isoniazid, etanercept, and intravenous immunoglobulin (IVIG) are therapies not currently supported by the literature.
Procedural management of HS includes intralesional steroid injections, botulinum toxin, laser therapy including laser hair removal, and wide local excision.
When treating a patient with HS, we should consider their medical comorbidities and complications of the disease. For patients with recalcitrant disease or who are not good surgical candidates, combination therapies and a multidisciplinary approach may be helpful.
Financial Tips for the Dermatologist
Jashin Wu, MD
Dr. Jashin Wu felt one should have 3-6 months of cash for living expenses in case of emergencies, but not too much in cash which earns little interest and loses value due to inflation, which is usually 2-3% each year. Inflation is very high at 7.5% in January 2022, a 40-year high.
Gold is a hedge against inflation, because its price tends to rise when the cost-of-living increases or the local currency is losing value. As storage of gold bars is an issue, it may be simpler to buy gold miner stocks. Cryptocurrency is also a good hedge against inflation.
It’s important to own your primary home, as the value of the property goes up over time, and there are tax benefits in owning a home and when selling a home. Interest rates were at historic lows last year, but are creeping up since.
Equities (stocks/mutual funds/ETFs) have more potential upside (5-10x or more return in a few years), but losses can be real, and stocks can go bankrupt.
Most people will have ~10 mutual funds offered in their 401k. Dr. Wu recommends picking just 1 or 2 index funds. For taxable accounts, for the investor who doesn’t have the time or inclination to pick stocks or bonds: he recommends Vanguard Total Stock Market Index Fund Institutional Shares (VITSX) (expense ratio 0.03%) and Vanguard Total Bond Market Index Fund Institutional Shares (VBTIX) (expense ratio 0.035%).
Don’t fight the Fed (Federal Reserve). When the Fed raises interest rates (started in January 2022), stocks tend to go down. High value stocks (high PE ratio) with no earnings tend (such as young tech companies) get slammed. Companies with solid earnings tend to weather the storm better.
Gold is a hedge against inflation, because its price tends to rise when the cost-of-living increases or the local currency is losing value. As storage of gold bars is an issue, it may be simpler to buy gold miner stocks. Cryptocurrency is also a good hedge against inflation.
It’s important to own your primary home, as the value of the property goes up over time, and there are tax benefits in owning a home and when selling a home. Interest rates were at historic lows last year, but are creeping up since.
Equities (stocks/mutual funds/ETFs) have more potential upside (5-10x or more return in a few years), but losses can be real, and stocks can go bankrupt.
Most people will have ~10 mutual funds offered in their 401k. Dr. Wu recommends picking just 1 or 2 index funds. For taxable accounts, for the investor who doesn’t have the time or inclination to pick stocks or bonds: he recommends Vanguard Total Stock Market Index Fund Institutional Shares (VITSX) (expense ratio 0.03%) and Vanguard Total Bond Market Index Fund Institutional Shares (VBTIX) (expense ratio 0.035%).
Don’t fight the Fed (Federal Reserve). When the Fed raises interest rates (started in January 2022), stocks tend to go down. High value stocks (high PE ratio) with no earnings tend (such as young tech companies) get slammed. Companies with solid earnings tend to weather the storm better.
Scarring Alopecia
Carolyn Goh, MD
Dr. Goh provided an excellent overview and case-based discussion on scarring alopecia. She discussed the challenges of scarring alopecia including diagnosis, treatment, and time management, and that it is considered a “trichologic emergency” due to permanent loss of hair that can progress unexpectedly and rapidly. Primary scarring alopecia is divided into those due to a neutrophilic, lymphocytic, or mixed infiltrate. Secondary scarring alopecia may occur due to trauma or tumors, morphea, late tinea capitis, and late traction or trichotillomania.
In terms of diagnosis, Dr. Goh recommended a focused history and physical to include timing/duration, presence of increased shedding, pattern of loss, associated symptoms, dermoscopy to determine scarring vs. non-scarring, and a hair pull test. She recommends two 4mm punch biopsies (one for horizontal sectioning, one for vertical sectioning) at an active edge, suggesting a more subacute location rather than a very active location.
Dr. Goh then led us through a series of clinical cases, which included diagnoses of frontal fibrosing alopecia, lichen planopilaris, central centrifugal cicatricial alopecia, chronic cutaneous lupus, folliculitis decalvans, and dissecting cellulitis of the scalp.
The goals of treatment are to reduce symptoms, slow the progression of hair loss, and maintain the hair that is present. Treatment options for lymphocytic scarring alopecias include topical and/or intralesional corticosteroids, topical calcineurin inhibitors, doxycycline or minocycline, hydroxychloroquine, pioglitazone, mycophenolate mofetil, methotrexate, cyclosporine, possibly JAK inhibitors, finasteride or dutasteride, topical metformin, cetirizine, omalizumab, apremilast, low-dose naltrexone, and treatment of underlying non-scarring alopecia. Treatment options for neutrophilic scarring alopecias include doxycycline or minocycline, clindamycin and rifampin, other antibiotics, topical clindamycin, topical and/or intralesional corticosteroids, surgical excision at times, isotretinoin or topical retinoids, TNF inhibitors for dissecting cellulitis, and dapsone. A helpful resource to provide patients is the website for the Cicatricial Alopecia Research Foundation (www.carfintl.org).
In terms of diagnosis, Dr. Goh recommended a focused history and physical to include timing/duration, presence of increased shedding, pattern of loss, associated symptoms, dermoscopy to determine scarring vs. non-scarring, and a hair pull test. She recommends two 4mm punch biopsies (one for horizontal sectioning, one for vertical sectioning) at an active edge, suggesting a more subacute location rather than a very active location.
Dr. Goh then led us through a series of clinical cases, which included diagnoses of frontal fibrosing alopecia, lichen planopilaris, central centrifugal cicatricial alopecia, chronic cutaneous lupus, folliculitis decalvans, and dissecting cellulitis of the scalp.
The goals of treatment are to reduce symptoms, slow the progression of hair loss, and maintain the hair that is present. Treatment options for lymphocytic scarring alopecias include topical and/or intralesional corticosteroids, topical calcineurin inhibitors, doxycycline or minocycline, hydroxychloroquine, pioglitazone, mycophenolate mofetil, methotrexate, cyclosporine, possibly JAK inhibitors, finasteride or dutasteride, topical metformin, cetirizine, omalizumab, apremilast, low-dose naltrexone, and treatment of underlying non-scarring alopecia. Treatment options for neutrophilic scarring alopecias include doxycycline or minocycline, clindamycin and rifampin, other antibiotics, topical clindamycin, topical and/or intralesional corticosteroids, surgical excision at times, isotretinoin or topical retinoids, TNF inhibitors for dissecting cellulitis, and dapsone. A helpful resource to provide patients is the website for the Cicatricial Alopecia Research Foundation (www.carfintl.org).
Poster of the Day
Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 (TYK2) Inhibitor, in Moderate to Severe Plaque Psoriasis: 52-Week Efficacy Results From the Phase 3 POETYK PSO-1 and PSO-2 Trials
Deucravacitinib is an oral selective inhibitor of tyrosine kinase 2 (TYK2), an intracellular enzyme that mediates signaling of cytokines involved in psoriasis pathogenesis. The objective of this study was to evaluate the efficacy of deucravactinib treatment over 52 weeks in the POETYK PSO-1 and PSO-2 trials. Adults with a diagnosis of moderate to severe plaque psoriasis and PASI ≥12, sPGA ≥3, body surface area (BSA) ≥10% were included.
In POETYK PSO-1, the primary endpoints (PASI 75 and sPGA 0/1 responses) as well as secondary efficacy endpoints (PASI 90, PASI 100, and sPGA 0 responses) were maintained through 52 weeks in patients treated with deucravacitinib. Patients who switched from placebo to deucravacitinib at Week 16 achieved comparable responses to those observed in patients who received continuous deucravacitinib treatment from Day 1.
In POETYK PSO-2, clinical responses were maintained in patients who achieved PASI 75 at Week 24 who received continuous treatment with deucravacitinib through Week 52. Durable responses were seen after withdrawal of treatment in Week 24 responders; median time to loss of PASI 75 response was 12 weeks.
In conclusion, deucravacitinib was found to be an effective treatment in patients with moderate to severe plaque psoriasis. Clinical responses improved through Week 24 and were maintained in patients receiving continuous treatment through Week 52, and through a median of 12 weeks after withdrawal of the drug. This is an exciting new once-daily oral drug that may be an efficacious and well-tolerated treatment option for our patients with psoriasis.
Deucravacitinib is an oral selective inhibitor of tyrosine kinase 2 (TYK2), an intracellular enzyme that mediates signaling of cytokines involved in psoriasis pathogenesis. The objective of this study was to evaluate the efficacy of deucravactinib treatment over 52 weeks in the POETYK PSO-1 and PSO-2 trials. Adults with a diagnosis of moderate to severe plaque psoriasis and PASI ≥12, sPGA ≥3, body surface area (BSA) ≥10% were included.
In POETYK PSO-1, the primary endpoints (PASI 75 and sPGA 0/1 responses) as well as secondary efficacy endpoints (PASI 90, PASI 100, and sPGA 0 responses) were maintained through 52 weeks in patients treated with deucravacitinib. Patients who switched from placebo to deucravacitinib at Week 16 achieved comparable responses to those observed in patients who received continuous deucravacitinib treatment from Day 1.
In POETYK PSO-2, clinical responses were maintained in patients who achieved PASI 75 at Week 24 who received continuous treatment with deucravacitinib through Week 52. Durable responses were seen after withdrawal of treatment in Week 24 responders; median time to loss of PASI 75 response was 12 weeks.
In conclusion, deucravacitinib was found to be an effective treatment in patients with moderate to severe plaque psoriasis. Clinical responses improved through Week 24 and were maintained in patients receiving continuous treatment through Week 52, and through a median of 12 weeks after withdrawal of the drug. This is an exciting new once-daily oral drug that may be an efficacious and well-tolerated treatment option for our patients with psoriasis.
