User login
Does Omalizumab Cause Atopic Dermatitis Flare-Ups?
To the Editor:
We read with interest the case reported by Yanovsky et al1 (Cutis. 2023;112:E23-E25). We thank the authors for updating our knowledge about atopic dermatitis (AD) and omalizumab and improving our understanding of the various wanted and unwanted effects that may manifest with omalizumab. We wish to clarify a few points on omalizumab use.
First, Yanovsky et al1 reported that their patient’s AD flares occurred within a few days after omalizumab injections to control asthma, possibly because omalizumab may have caused a paradoxical increase in sensitivity to other cytokines such as IL-33 in basophils and increased IL-4/IL-13 production in the skin. The authors cited Imai2 to explain that IL-33 plays a role in the pathogenesis of AD, increases itching, and disrupts the skin barrier. However, Imai2 did not discuss a relationship with omalizumab. As a recombinant humanized IgG1 monoclonal anti-IgE antibody, omalizumab works by interacting with the high-affinity receptor Fc epsilon RI that typically is found on eosinophils, mast cells, and basophils and plays a critical role in preventing the allergic cascade.3 We could not find any studies in the literature regarding omalizumab having a specific effect on the skin, causing cytokine imbalance, or increasing IL-4/IL-13 levels.
Second, the case report indicated that AD lesions improved with the biologic dupilumab,1 which seems amazing. Dupilumab is a monoclonal antibody used in patients with moderate to severe AD that blocks IL-4/IL-13 signaling and thus inhibits receptor signaling downstream of the Janus kinase signal transducer and activator of transcription protein pathway.4 It also has been shown to be beneficial in children with moderate to severe uncontrolled asthma.5 In vivo studies are needed to learn about the effects of these biologics on asthma and AD, whose complex immunologic effects are increasingly well understood by real patient experience.
Third, omalizumab has been found to relieve AD, not exacerbate it, in our own experience with 7 patients (unpublished data, 2024) and randomized controlled trials.6
Fourth, Yanovsky et al1 reported that the patient’s lesions flared up within a few days after taking omalizumab, which suggests a non-IgE delayed reaction. Could this reaction be related to polysorbate 20 used as an excipient in the commercial preparation? When we examined both preparations, the presence of polysorbate 80 in dupilumab was noteworthy,7 unlike omalizumab. We suggest the authors perform a patch test including polysorbate 20 and polysorbate 80.
Finally, the authors mentioned that omalizumab may cause a paradoxical exacerbation of AD in certain patients, as in tumor necrosis factor α inhibitor–induced psoriasis.8 This has been reported,8 but tumor necrosis factor α inhibitors are cytokine inhibitors and can lead to cytokine imbalance, while omalizumab is an IgE inhibitor.
Yanovsky et al1 described AD flares as “triggered by omalizumab,” which we believe was not the case. Because this patient had chronic AD, other causes of AD exacerbation in this patient could include stress or infection. Also, when they say that AD is triggered or induced, it implies that they are attributing the occurrence/development of AD in this patient to omalizumab. Of course, this also is not true.
Author’s Response
Thank you for your thoughtful comments. Although we agree that we cannot prove omalizumab was the cause of our patient’s AD flares, the new onset of severely worsening disease that was exacerbated by each dose of omalizumab as well as subsequent resolution upon switching to dupilumab was highly suggestive for a causal relationship. Our goal was to alert physicians to the possibility of this phenomenon and to encourage further study.
Karen A. Chernoff, MD
From the Department of Dermatology, Weill Cornell Medical College, New York, New York.
The author has no relevant financial disclosures to report.
- Yanovsky RL, Mitre M, Chernoff KA. Atopic dermatitis triggered by omalizumab and treated with dupilumab. Cutis. 2023;112:E23-E25. 2. Imai Y. Interleukin-33 in atopic dermatitis. J Dermatol Sci. 2019;96:2-7.
- Kumar C, Zito PM. Omalizumab. In: StatPearls [internet]. StatPearls Publishing; 2024.
- Seegräber M, Srour J, Walter A, et al. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol. 2018;11:467-474.
- Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021;385:2230-2240.
- Chan SMH, Cro S, Cornelius V, et al. Omalizumab for severe atopic dermatitis in 4- to 19-year-olds: the ADAPT RCT. National Institute for Health and Care Research; May 2022.
- Sumi T, Nagahisa Y, Matsuura K, et al. Delayed local reaction at a previous injection site reaction with dupilumab. Respirol Case Rep. 2021;9:E0852.
- Lian N, Zhang L, Chen M. Tumor necrosis factors-α inhibition-induced paradoxical psoriasis: a case series and literature review. Dermatol Ther. 2020;33:e14225.
To the Editor:
We read with interest the case reported by Yanovsky et al1 (Cutis. 2023;112:E23-E25). We thank the authors for updating our knowledge about atopic dermatitis (AD) and omalizumab and improving our understanding of the various wanted and unwanted effects that may manifest with omalizumab. We wish to clarify a few points on omalizumab use.
First, Yanovsky et al1 reported that their patient’s AD flares occurred within a few days after omalizumab injections to control asthma, possibly because omalizumab may have caused a paradoxical increase in sensitivity to other cytokines such as IL-33 in basophils and increased IL-4/IL-13 production in the skin. The authors cited Imai2 to explain that IL-33 plays a role in the pathogenesis of AD, increases itching, and disrupts the skin barrier. However, Imai2 did not discuss a relationship with omalizumab. As a recombinant humanized IgG1 monoclonal anti-IgE antibody, omalizumab works by interacting with the high-affinity receptor Fc epsilon RI that typically is found on eosinophils, mast cells, and basophils and plays a critical role in preventing the allergic cascade.3 We could not find any studies in the literature regarding omalizumab having a specific effect on the skin, causing cytokine imbalance, or increasing IL-4/IL-13 levels.
Second, the case report indicated that AD lesions improved with the biologic dupilumab,1 which seems amazing. Dupilumab is a monoclonal antibody used in patients with moderate to severe AD that blocks IL-4/IL-13 signaling and thus inhibits receptor signaling downstream of the Janus kinase signal transducer and activator of transcription protein pathway.4 It also has been shown to be beneficial in children with moderate to severe uncontrolled asthma.5 In vivo studies are needed to learn about the effects of these biologics on asthma and AD, whose complex immunologic effects are increasingly well understood by real patient experience.
Third, omalizumab has been found to relieve AD, not exacerbate it, in our own experience with 7 patients (unpublished data, 2024) and randomized controlled trials.6
Fourth, Yanovsky et al1 reported that the patient’s lesions flared up within a few days after taking omalizumab, which suggests a non-IgE delayed reaction. Could this reaction be related to polysorbate 20 used as an excipient in the commercial preparation? When we examined both preparations, the presence of polysorbate 80 in dupilumab was noteworthy,7 unlike omalizumab. We suggest the authors perform a patch test including polysorbate 20 and polysorbate 80.
Finally, the authors mentioned that omalizumab may cause a paradoxical exacerbation of AD in certain patients, as in tumor necrosis factor α inhibitor–induced psoriasis.8 This has been reported,8 but tumor necrosis factor α inhibitors are cytokine inhibitors and can lead to cytokine imbalance, while omalizumab is an IgE inhibitor.
Yanovsky et al1 described AD flares as “triggered by omalizumab,” which we believe was not the case. Because this patient had chronic AD, other causes of AD exacerbation in this patient could include stress or infection. Also, when they say that AD is triggered or induced, it implies that they are attributing the occurrence/development of AD in this patient to omalizumab. Of course, this also is not true.
Author’s Response
Thank you for your thoughtful comments. Although we agree that we cannot prove omalizumab was the cause of our patient’s AD flares, the new onset of severely worsening disease that was exacerbated by each dose of omalizumab as well as subsequent resolution upon switching to dupilumab was highly suggestive for a causal relationship. Our goal was to alert physicians to the possibility of this phenomenon and to encourage further study.
Karen A. Chernoff, MD
From the Department of Dermatology, Weill Cornell Medical College, New York, New York.
The author has no relevant financial disclosures to report.
To the Editor:
We read with interest the case reported by Yanovsky et al1 (Cutis. 2023;112:E23-E25). We thank the authors for updating our knowledge about atopic dermatitis (AD) and omalizumab and improving our understanding of the various wanted and unwanted effects that may manifest with omalizumab. We wish to clarify a few points on omalizumab use.
First, Yanovsky et al1 reported that their patient’s AD flares occurred within a few days after omalizumab injections to control asthma, possibly because omalizumab may have caused a paradoxical increase in sensitivity to other cytokines such as IL-33 in basophils and increased IL-4/IL-13 production in the skin. The authors cited Imai2 to explain that IL-33 plays a role in the pathogenesis of AD, increases itching, and disrupts the skin barrier. However, Imai2 did not discuss a relationship with omalizumab. As a recombinant humanized IgG1 monoclonal anti-IgE antibody, omalizumab works by interacting with the high-affinity receptor Fc epsilon RI that typically is found on eosinophils, mast cells, and basophils and plays a critical role in preventing the allergic cascade.3 We could not find any studies in the literature regarding omalizumab having a specific effect on the skin, causing cytokine imbalance, or increasing IL-4/IL-13 levels.
Second, the case report indicated that AD lesions improved with the biologic dupilumab,1 which seems amazing. Dupilumab is a monoclonal antibody used in patients with moderate to severe AD that blocks IL-4/IL-13 signaling and thus inhibits receptor signaling downstream of the Janus kinase signal transducer and activator of transcription protein pathway.4 It also has been shown to be beneficial in children with moderate to severe uncontrolled asthma.5 In vivo studies are needed to learn about the effects of these biologics on asthma and AD, whose complex immunologic effects are increasingly well understood by real patient experience.
Third, omalizumab has been found to relieve AD, not exacerbate it, in our own experience with 7 patients (unpublished data, 2024) and randomized controlled trials.6
Fourth, Yanovsky et al1 reported that the patient’s lesions flared up within a few days after taking omalizumab, which suggests a non-IgE delayed reaction. Could this reaction be related to polysorbate 20 used as an excipient in the commercial preparation? When we examined both preparations, the presence of polysorbate 80 in dupilumab was noteworthy,7 unlike omalizumab. We suggest the authors perform a patch test including polysorbate 20 and polysorbate 80.
Finally, the authors mentioned that omalizumab may cause a paradoxical exacerbation of AD in certain patients, as in tumor necrosis factor α inhibitor–induced psoriasis.8 This has been reported,8 but tumor necrosis factor α inhibitors are cytokine inhibitors and can lead to cytokine imbalance, while omalizumab is an IgE inhibitor.
Yanovsky et al1 described AD flares as “triggered by omalizumab,” which we believe was not the case. Because this patient had chronic AD, other causes of AD exacerbation in this patient could include stress or infection. Also, when they say that AD is triggered or induced, it implies that they are attributing the occurrence/development of AD in this patient to omalizumab. Of course, this also is not true.
Author’s Response
Thank you for your thoughtful comments. Although we agree that we cannot prove omalizumab was the cause of our patient’s AD flares, the new onset of severely worsening disease that was exacerbated by each dose of omalizumab as well as subsequent resolution upon switching to dupilumab was highly suggestive for a causal relationship. Our goal was to alert physicians to the possibility of this phenomenon and to encourage further study.
Karen A. Chernoff, MD
From the Department of Dermatology, Weill Cornell Medical College, New York, New York.
The author has no relevant financial disclosures to report.
- Yanovsky RL, Mitre M, Chernoff KA. Atopic dermatitis triggered by omalizumab and treated with dupilumab. Cutis. 2023;112:E23-E25. 2. Imai Y. Interleukin-33 in atopic dermatitis. J Dermatol Sci. 2019;96:2-7.
- Kumar C, Zito PM. Omalizumab. In: StatPearls [internet]. StatPearls Publishing; 2024.
- Seegräber M, Srour J, Walter A, et al. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol. 2018;11:467-474.
- Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021;385:2230-2240.
- Chan SMH, Cro S, Cornelius V, et al. Omalizumab for severe atopic dermatitis in 4- to 19-year-olds: the ADAPT RCT. National Institute for Health and Care Research; May 2022.
- Sumi T, Nagahisa Y, Matsuura K, et al. Delayed local reaction at a previous injection site reaction with dupilumab. Respirol Case Rep. 2021;9:E0852.
- Lian N, Zhang L, Chen M. Tumor necrosis factors-α inhibition-induced paradoxical psoriasis: a case series and literature review. Dermatol Ther. 2020;33:e14225.
- Yanovsky RL, Mitre M, Chernoff KA. Atopic dermatitis triggered by omalizumab and treated with dupilumab. Cutis. 2023;112:E23-E25. 2. Imai Y. Interleukin-33 in atopic dermatitis. J Dermatol Sci. 2019;96:2-7.
- Kumar C, Zito PM. Omalizumab. In: StatPearls [internet]. StatPearls Publishing; 2024.
- Seegräber M, Srour J, Walter A, et al. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol. 2018;11:467-474.
- Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021;385:2230-2240.
- Chan SMH, Cro S, Cornelius V, et al. Omalizumab for severe atopic dermatitis in 4- to 19-year-olds: the ADAPT RCT. National Institute for Health and Care Research; May 2022.
- Sumi T, Nagahisa Y, Matsuura K, et al. Delayed local reaction at a previous injection site reaction with dupilumab. Respirol Case Rep. 2021;9:E0852.
- Lian N, Zhang L, Chen M. Tumor necrosis factors-α inhibition-induced paradoxical psoriasis: a case series and literature review. Dermatol Ther. 2020;33:e14225.
Mental Health Services: The Missing Piece or Missing Peace for Patients With Atopic Dermatitis
There is a well-established connection between the mind and the skin, and it is clear that this relationship is bidirectional—not only does skin disease increase the risk for depression, anxiety, sleep disturbance, and suicidality, but psychologic stress actually can worsen skin disease through multiple mechanisms, including direct damage to the skin barrier.1,2 Psychologic stress also impacts the microbiome, another critical driver of skin disease.3,4 The concept of the itch-scratch cycle vividly illustrates the vicious interplay between the mind and body in atopic dermatitis (AD).
However, patients with AD are not the only ones impacted—caregivers also experience psychologic stress. Remarkably, one study of patients with AD and their caregivers found that the caregivers actually reported significantly worse mental health and anxiety (P=.01 and P=.03, respectively) than patients themselves, even when controlling for the severity of disease.5
Thus, it would seem obvious for mental health to be a central component of AD care—to improve patient and caregiver quality of life while also improving symptoms. Research has actually borne this out, with one systematic review and meta-analysis concluding that psychological intervention has a beneficial effect on AD,6 and another that the addition of psychological and educational interventions to conventional treatment provided better therapeutic results in alleviating eczema severity and psychological symptoms.7 One study demonstrated that patients with AD who received cognitive behavioral therapy via the internet displayed a statistically significant improvement in their disease (P<.001) as measured by the Patient-Oriented Eczema Measure compared with those in the control group who received standard care alone. They also reported improvements in perceived stress, sleep problems, and depression in the intervention group that were sustained at 1-year follow-up.8 These findings are particularly impactful because clinical results were achieved while leveraging an internet-based approach to therapy.
Regrettably, despite the preponderance of evidence supporting the connection between mental health and AD, there remain considerable unmet needs. A recent cross-sectional survey of 954 adults with AD and caregivers of children with AD (N=954) conducted by the National Eczema Association found that half of patients were never asked about mental health during any of their visits, and of those referred for mental health resources, only 57% utilized the recommended services.9 Importantly, patients aged 18 to 34 years reported wanting to be asked about mental health. Of those who did receive referrals, most were for counseling services (23%), followed by alternative mental health therapy such as music or art therapy (15%), cognitive behavioral therapy (13%), or peer/social support groups (12%). Approximately 10% reported receiving a pamphlet or a brochure only.9
Physicians who treat patients with AD can and must do better, but first we must explore why these referral rates are so low. As with many complex problems, there is unlikely to be one simple unifying reason. As expected, the answer is nuanced and multifaceted, and—most importantly—staggeringly incomplete.
For starters, mental health interventions rarely are as easy as applying a cream or taking a pill. Hedman-Lagerlöf et al8 specifically pointed out that although their approach—using internet-based cognitive behavioral therapy—was explicitly designed to be more accessible with fewer resources, it required approximately 35 hours of treatment over 12 weeks, requiring both substantial time and commitment from patients who often are already burned out and exhausted due to AD. They even underscored that the most commonly reported adverse effect of therapy was increased stress or worry, making it a difficult sell.8
Even before most patients have a chance to consider the time required and the potential adverse effects of mental health interventions for AD, greater hurdles exist. Finances, medical insurance, and wait times were highlighted as barriers to care in a systematic review.10 These are deep-seated problems in the United States; while they may be surmountable in certain geographic areas, the frequency with which these concerns arise means that it does not take too many failed attempts at referring patients for mental health services before clinicians just give up—similar to any form of operant conditioning.
A more elusive concept is stigmatization. Although it may not be quantifiable, the idea is that patients may encounter additional challenges when seeking mental health care, either because the interactions themselves may worsen their symptoms (eg, increased anxiety) or they may be more likely to have a negative perception of the experience.11 A 2020 systematic review of barriers to addressing common mental health problems found that stigma was the most prominent barrier in adolescents, with the second most prominent being negative attitudes and beliefs about mental health services and professionals.12 As a clinician, I can attest that I have sometimes detected skepticism when I have suggested mental health services to patients and have even been asked outright if I thought the problem was all in their head. My patients with AD generally have been much more open to the idea of mental health support, especially after I explain the powerful mind-body connection, than patients with other conditions—most notably delusions of parasitosis—who have been much more dismissive of such overtures. An oft-cited paper from 1976 frames the problem perfectly, describing what can happen after a referral for mental health services.13 The authors stated that the suggestion of mental health makes patients feel that the dermatologist does not believe them in the first place. Beyond this, the authors pointed out that referring the patient elsewhere reduces their hopes for dermatologic treatment.13
Knowing now—perhaps more than ever before—that the mind and skin are intimately connected compels us to solve these problems and find ways around these obstacles. Selecting the optimal forms of mental health services for each patient, having the structural support of the health care system, and winning the trust of patients and caregivers while combating stigma are undoubtedly tall orders; however, understanding the stakes for patients with AD, their caregivers, and society as a whole should inspire us to keep pushing forward.
- Nicholas MN, Gooderham MJ. Atopic dermatitis, depression, and suicidality. J Cutan Med Surg. 2017;21:237-242. doi:10.1177/1203475416685078
- aarouf M, Maarouf CL, Yosipovitch G, et al. The impact of stress on epidermal barrier function: an evidence‐based review. Br J Dermatol. 2019;181:1129-1137.
- Prescott SL, Larcombe DL, Logan AC, et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017;10:29.
- Zhang XE, Zheng P, Ye SZ, et al. Microbiome: role in inflammatory skin diseases. J Inflamm Res. 2024;17:1057-1082.
- Chong AC, Schwartz A, Lang J, et al. Patients’ and caregivers’ preferences for mental health care and support in atopic dermatitis. Dermatitis. 2024;35(suppl 1):S70-S76.
- Chida Y, Steptoe A, Hirakawa N, et al. The effects of psychological intervention on atopic dermatitis. a systematic review and meta-analysis. Int Arch Allergy Immunol. 2007;144:1-9.
- Hashimoto K, Ogawa Y, Takeshima N, et al. Psychological and educational interventions for atopic dermatitis in adults: a systematic review and meta-analysis. Behav Change. 2017;34:48-65.
- Hedman-Lagerlöf E, Fust J, Axelsson E, et al. Internet-delivered cognitive behavior therapy for atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157:796-804. doi:10.1001/jamadermatol.2021.1450
- Chatrath S, Loiselle AR, Johnson JK, et al. Evaluating mental health support by healthcare providers for patients with atopic dermatitis: a cross‐sectional survey. Skin Health Dis. Published online June 15, 2024. doi:10.1002/ski2.408
- Toy J, Gregory A, Rehmus W. Barriers to healthcare access in pediatric dermatology: a systematic review. Pediatr Dermatol. 2021;38(suppl 2):13-19.
- Borba CPC, DePadilla L, McCarty FA, et al. A qualitative study examining the perceived barriers and facilitators to medical healthcare services among women with a serious mental illness. Womens Health Issues. 2012;22:E217-E224.
- Aguirre Velasco A, Cruz ISS, Billings J, et al. What are the barriers, facilitators and interventions targeting help-seeking behaviours for common mental health problems in adolescents? a systematic review. BMC Psychiatry. 2020;20:293.
- Gould WM, Gragg TM. Delusions of parasitosis. an approach to the problem. Arch Dermatol. 1976;112:1745-1748.
There is a well-established connection between the mind and the skin, and it is clear that this relationship is bidirectional—not only does skin disease increase the risk for depression, anxiety, sleep disturbance, and suicidality, but psychologic stress actually can worsen skin disease through multiple mechanisms, including direct damage to the skin barrier.1,2 Psychologic stress also impacts the microbiome, another critical driver of skin disease.3,4 The concept of the itch-scratch cycle vividly illustrates the vicious interplay between the mind and body in atopic dermatitis (AD).
However, patients with AD are not the only ones impacted—caregivers also experience psychologic stress. Remarkably, one study of patients with AD and their caregivers found that the caregivers actually reported significantly worse mental health and anxiety (P=.01 and P=.03, respectively) than patients themselves, even when controlling for the severity of disease.5
Thus, it would seem obvious for mental health to be a central component of AD care—to improve patient and caregiver quality of life while also improving symptoms. Research has actually borne this out, with one systematic review and meta-analysis concluding that psychological intervention has a beneficial effect on AD,6 and another that the addition of psychological and educational interventions to conventional treatment provided better therapeutic results in alleviating eczema severity and psychological symptoms.7 One study demonstrated that patients with AD who received cognitive behavioral therapy via the internet displayed a statistically significant improvement in their disease (P<.001) as measured by the Patient-Oriented Eczema Measure compared with those in the control group who received standard care alone. They also reported improvements in perceived stress, sleep problems, and depression in the intervention group that were sustained at 1-year follow-up.8 These findings are particularly impactful because clinical results were achieved while leveraging an internet-based approach to therapy.
Regrettably, despite the preponderance of evidence supporting the connection between mental health and AD, there remain considerable unmet needs. A recent cross-sectional survey of 954 adults with AD and caregivers of children with AD (N=954) conducted by the National Eczema Association found that half of patients were never asked about mental health during any of their visits, and of those referred for mental health resources, only 57% utilized the recommended services.9 Importantly, patients aged 18 to 34 years reported wanting to be asked about mental health. Of those who did receive referrals, most were for counseling services (23%), followed by alternative mental health therapy such as music or art therapy (15%), cognitive behavioral therapy (13%), or peer/social support groups (12%). Approximately 10% reported receiving a pamphlet or a brochure only.9
Physicians who treat patients with AD can and must do better, but first we must explore why these referral rates are so low. As with many complex problems, there is unlikely to be one simple unifying reason. As expected, the answer is nuanced and multifaceted, and—most importantly—staggeringly incomplete.
For starters, mental health interventions rarely are as easy as applying a cream or taking a pill. Hedman-Lagerlöf et al8 specifically pointed out that although their approach—using internet-based cognitive behavioral therapy—was explicitly designed to be more accessible with fewer resources, it required approximately 35 hours of treatment over 12 weeks, requiring both substantial time and commitment from patients who often are already burned out and exhausted due to AD. They even underscored that the most commonly reported adverse effect of therapy was increased stress or worry, making it a difficult sell.8
Even before most patients have a chance to consider the time required and the potential adverse effects of mental health interventions for AD, greater hurdles exist. Finances, medical insurance, and wait times were highlighted as barriers to care in a systematic review.10 These are deep-seated problems in the United States; while they may be surmountable in certain geographic areas, the frequency with which these concerns arise means that it does not take too many failed attempts at referring patients for mental health services before clinicians just give up—similar to any form of operant conditioning.
A more elusive concept is stigmatization. Although it may not be quantifiable, the idea is that patients may encounter additional challenges when seeking mental health care, either because the interactions themselves may worsen their symptoms (eg, increased anxiety) or they may be more likely to have a negative perception of the experience.11 A 2020 systematic review of barriers to addressing common mental health problems found that stigma was the most prominent barrier in adolescents, with the second most prominent being negative attitudes and beliefs about mental health services and professionals.12 As a clinician, I can attest that I have sometimes detected skepticism when I have suggested mental health services to patients and have even been asked outright if I thought the problem was all in their head. My patients with AD generally have been much more open to the idea of mental health support, especially after I explain the powerful mind-body connection, than patients with other conditions—most notably delusions of parasitosis—who have been much more dismissive of such overtures. An oft-cited paper from 1976 frames the problem perfectly, describing what can happen after a referral for mental health services.13 The authors stated that the suggestion of mental health makes patients feel that the dermatologist does not believe them in the first place. Beyond this, the authors pointed out that referring the patient elsewhere reduces their hopes for dermatologic treatment.13
Knowing now—perhaps more than ever before—that the mind and skin are intimately connected compels us to solve these problems and find ways around these obstacles. Selecting the optimal forms of mental health services for each patient, having the structural support of the health care system, and winning the trust of patients and caregivers while combating stigma are undoubtedly tall orders; however, understanding the stakes for patients with AD, their caregivers, and society as a whole should inspire us to keep pushing forward.
There is a well-established connection between the mind and the skin, and it is clear that this relationship is bidirectional—not only does skin disease increase the risk for depression, anxiety, sleep disturbance, and suicidality, but psychologic stress actually can worsen skin disease through multiple mechanisms, including direct damage to the skin barrier.1,2 Psychologic stress also impacts the microbiome, another critical driver of skin disease.3,4 The concept of the itch-scratch cycle vividly illustrates the vicious interplay between the mind and body in atopic dermatitis (AD).
However, patients with AD are not the only ones impacted—caregivers also experience psychologic stress. Remarkably, one study of patients with AD and their caregivers found that the caregivers actually reported significantly worse mental health and anxiety (P=.01 and P=.03, respectively) than patients themselves, even when controlling for the severity of disease.5
Thus, it would seem obvious for mental health to be a central component of AD care—to improve patient and caregiver quality of life while also improving symptoms. Research has actually borne this out, with one systematic review and meta-analysis concluding that psychological intervention has a beneficial effect on AD,6 and another that the addition of psychological and educational interventions to conventional treatment provided better therapeutic results in alleviating eczema severity and psychological symptoms.7 One study demonstrated that patients with AD who received cognitive behavioral therapy via the internet displayed a statistically significant improvement in their disease (P<.001) as measured by the Patient-Oriented Eczema Measure compared with those in the control group who received standard care alone. They also reported improvements in perceived stress, sleep problems, and depression in the intervention group that were sustained at 1-year follow-up.8 These findings are particularly impactful because clinical results were achieved while leveraging an internet-based approach to therapy.
Regrettably, despite the preponderance of evidence supporting the connection between mental health and AD, there remain considerable unmet needs. A recent cross-sectional survey of 954 adults with AD and caregivers of children with AD (N=954) conducted by the National Eczema Association found that half of patients were never asked about mental health during any of their visits, and of those referred for mental health resources, only 57% utilized the recommended services.9 Importantly, patients aged 18 to 34 years reported wanting to be asked about mental health. Of those who did receive referrals, most were for counseling services (23%), followed by alternative mental health therapy such as music or art therapy (15%), cognitive behavioral therapy (13%), or peer/social support groups (12%). Approximately 10% reported receiving a pamphlet or a brochure only.9
Physicians who treat patients with AD can and must do better, but first we must explore why these referral rates are so low. As with many complex problems, there is unlikely to be one simple unifying reason. As expected, the answer is nuanced and multifaceted, and—most importantly—staggeringly incomplete.
For starters, mental health interventions rarely are as easy as applying a cream or taking a pill. Hedman-Lagerlöf et al8 specifically pointed out that although their approach—using internet-based cognitive behavioral therapy—was explicitly designed to be more accessible with fewer resources, it required approximately 35 hours of treatment over 12 weeks, requiring both substantial time and commitment from patients who often are already burned out and exhausted due to AD. They even underscored that the most commonly reported adverse effect of therapy was increased stress or worry, making it a difficult sell.8
Even before most patients have a chance to consider the time required and the potential adverse effects of mental health interventions for AD, greater hurdles exist. Finances, medical insurance, and wait times were highlighted as barriers to care in a systematic review.10 These are deep-seated problems in the United States; while they may be surmountable in certain geographic areas, the frequency with which these concerns arise means that it does not take too many failed attempts at referring patients for mental health services before clinicians just give up—similar to any form of operant conditioning.
A more elusive concept is stigmatization. Although it may not be quantifiable, the idea is that patients may encounter additional challenges when seeking mental health care, either because the interactions themselves may worsen their symptoms (eg, increased anxiety) or they may be more likely to have a negative perception of the experience.11 A 2020 systematic review of barriers to addressing common mental health problems found that stigma was the most prominent barrier in adolescents, with the second most prominent being negative attitudes and beliefs about mental health services and professionals.12 As a clinician, I can attest that I have sometimes detected skepticism when I have suggested mental health services to patients and have even been asked outright if I thought the problem was all in their head. My patients with AD generally have been much more open to the idea of mental health support, especially after I explain the powerful mind-body connection, than patients with other conditions—most notably delusions of parasitosis—who have been much more dismissive of such overtures. An oft-cited paper from 1976 frames the problem perfectly, describing what can happen after a referral for mental health services.13 The authors stated that the suggestion of mental health makes patients feel that the dermatologist does not believe them in the first place. Beyond this, the authors pointed out that referring the patient elsewhere reduces their hopes for dermatologic treatment.13
Knowing now—perhaps more than ever before—that the mind and skin are intimately connected compels us to solve these problems and find ways around these obstacles. Selecting the optimal forms of mental health services for each patient, having the structural support of the health care system, and winning the trust of patients and caregivers while combating stigma are undoubtedly tall orders; however, understanding the stakes for patients with AD, their caregivers, and society as a whole should inspire us to keep pushing forward.
- Nicholas MN, Gooderham MJ. Atopic dermatitis, depression, and suicidality. J Cutan Med Surg. 2017;21:237-242. doi:10.1177/1203475416685078
- aarouf M, Maarouf CL, Yosipovitch G, et al. The impact of stress on epidermal barrier function: an evidence‐based review. Br J Dermatol. 2019;181:1129-1137.
- Prescott SL, Larcombe DL, Logan AC, et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017;10:29.
- Zhang XE, Zheng P, Ye SZ, et al. Microbiome: role in inflammatory skin diseases. J Inflamm Res. 2024;17:1057-1082.
- Chong AC, Schwartz A, Lang J, et al. Patients’ and caregivers’ preferences for mental health care and support in atopic dermatitis. Dermatitis. 2024;35(suppl 1):S70-S76.
- Chida Y, Steptoe A, Hirakawa N, et al. The effects of psychological intervention on atopic dermatitis. a systematic review and meta-analysis. Int Arch Allergy Immunol. 2007;144:1-9.
- Hashimoto K, Ogawa Y, Takeshima N, et al. Psychological and educational interventions for atopic dermatitis in adults: a systematic review and meta-analysis. Behav Change. 2017;34:48-65.
- Hedman-Lagerlöf E, Fust J, Axelsson E, et al. Internet-delivered cognitive behavior therapy for atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157:796-804. doi:10.1001/jamadermatol.2021.1450
- Chatrath S, Loiselle AR, Johnson JK, et al. Evaluating mental health support by healthcare providers for patients with atopic dermatitis: a cross‐sectional survey. Skin Health Dis. Published online June 15, 2024. doi:10.1002/ski2.408
- Toy J, Gregory A, Rehmus W. Barriers to healthcare access in pediatric dermatology: a systematic review. Pediatr Dermatol. 2021;38(suppl 2):13-19.
- Borba CPC, DePadilla L, McCarty FA, et al. A qualitative study examining the perceived barriers and facilitators to medical healthcare services among women with a serious mental illness. Womens Health Issues. 2012;22:E217-E224.
- Aguirre Velasco A, Cruz ISS, Billings J, et al. What are the barriers, facilitators and interventions targeting help-seeking behaviours for common mental health problems in adolescents? a systematic review. BMC Psychiatry. 2020;20:293.
- Gould WM, Gragg TM. Delusions of parasitosis. an approach to the problem. Arch Dermatol. 1976;112:1745-1748.
- Nicholas MN, Gooderham MJ. Atopic dermatitis, depression, and suicidality. J Cutan Med Surg. 2017;21:237-242. doi:10.1177/1203475416685078
- aarouf M, Maarouf CL, Yosipovitch G, et al. The impact of stress on epidermal barrier function: an evidence‐based review. Br J Dermatol. 2019;181:1129-1137.
- Prescott SL, Larcombe DL, Logan AC, et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017;10:29.
- Zhang XE, Zheng P, Ye SZ, et al. Microbiome: role in inflammatory skin diseases. J Inflamm Res. 2024;17:1057-1082.
- Chong AC, Schwartz A, Lang J, et al. Patients’ and caregivers’ preferences for mental health care and support in atopic dermatitis. Dermatitis. 2024;35(suppl 1):S70-S76.
- Chida Y, Steptoe A, Hirakawa N, et al. The effects of psychological intervention on atopic dermatitis. a systematic review and meta-analysis. Int Arch Allergy Immunol. 2007;144:1-9.
- Hashimoto K, Ogawa Y, Takeshima N, et al. Psychological and educational interventions for atopic dermatitis in adults: a systematic review and meta-analysis. Behav Change. 2017;34:48-65.
- Hedman-Lagerlöf E, Fust J, Axelsson E, et al. Internet-delivered cognitive behavior therapy for atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021;157:796-804. doi:10.1001/jamadermatol.2021.1450
- Chatrath S, Loiselle AR, Johnson JK, et al. Evaluating mental health support by healthcare providers for patients with atopic dermatitis: a cross‐sectional survey. Skin Health Dis. Published online June 15, 2024. doi:10.1002/ski2.408
- Toy J, Gregory A, Rehmus W. Barriers to healthcare access in pediatric dermatology: a systematic review. Pediatr Dermatol. 2021;38(suppl 2):13-19.
- Borba CPC, DePadilla L, McCarty FA, et al. A qualitative study examining the perceived barriers and facilitators to medical healthcare services among women with a serious mental illness. Womens Health Issues. 2012;22:E217-E224.
- Aguirre Velasco A, Cruz ISS, Billings J, et al. What are the barriers, facilitators and interventions targeting help-seeking behaviours for common mental health problems in adolescents? a systematic review. BMC Psychiatry. 2020;20:293.
- Gould WM, Gragg TM. Delusions of parasitosis. an approach to the problem. Arch Dermatol. 1976;112:1745-1748.
Practice Points
- The mind-body connection plays a role in many conditions, including atopic dermatitis.
- Atopic dermatitis can make patients feel anxious, stressed, and depressed; at the same time, those feelings can lead to worsening of the condition.
- There are many barriers to getting mental health care in the United States, from financial constraints to stigmatization.
- Mental health is part of overall health and should be more highly prioritized by all physicians.
“It Takes a Village”: Benefits and Challenges of Navigating Cancer Care with the Pacific Community and the Veterans Health Administration
Background
The Palliative Care in Hawaii/Pacific Island Communities for Veterans (PaCiHPIC Veterans) study is a VA-funded research study that explores social determinants of health, cultural values, and cancer disparities impacting Native Hawaiian/Pacific Islander/US-affiliated Pacific Island resident (NHPI/USAPI) Veterans.Cancer prevalence and mortality are increasing among NHPI/ USAPI Veterans which can be partly attributed to nuclear fallout from U.S. military activities in the region. This population faces geographic, financial, and logistical barriers to cancer care. There is an imminent need to understand and address access to cancer care and palliative care to reduce disparities within this population.
Methods
We interviewed 15 clinicians including physicians, nurses, nurse practitioners, social workers, and clinical psychologists specializing in primary care, palliative care, and oncology, self-identifying as White, Asian American, NHPI, and Multiracial. Interviews were transcribed verbatim and de-identified. Using inductive and deductive strategies, we iteratively collapsed content into codes formulating a codebook. Thematic analyses were performed using dual-coder review in Atlas.ti v23. Themes were mapped to the socioecological model.
Results
Clinicians described how NHPI/USAPI Veterans receive healthcare and instrumental support at individual, community, and systems levels, including from family caregivers, “high-talking chiefs,” traditional healers (“suruhanu”), community health clinics, and the VHA. Clinicians identified challenges and opportunities for care coordination: (1) financial and logistical barriers to involve family and decision-makers; (2) clinician understanding of cultural values and influence on medical decision-making; (3) care fragmentation resulting from transitions between community care and VHA; and (4) collaboration with key individuals in Pacific social hierarchies.
Conclusions
Cancer navigation and care coordination gaps create challenges for clinicians and NHPI/USAPI Veterans managing cancer in the Pacific Islands. Better understanding of these systems of care and associated gaps can inform the development of an intervention to improve cancer care delivery to this population. NHPI/ USAPI Veterans may experience care fragmentation due to care transitions between community care and the VHA. At the same time, these sources also create multiple layers of support for Veterans. Interventions to address these challenges can leverage the strengths of Pacific communities, while striving to better integrate care between community healthcare providers and VHA.
Background
The Palliative Care in Hawaii/Pacific Island Communities for Veterans (PaCiHPIC Veterans) study is a VA-funded research study that explores social determinants of health, cultural values, and cancer disparities impacting Native Hawaiian/Pacific Islander/US-affiliated Pacific Island resident (NHPI/USAPI) Veterans.Cancer prevalence and mortality are increasing among NHPI/ USAPI Veterans which can be partly attributed to nuclear fallout from U.S. military activities in the region. This population faces geographic, financial, and logistical barriers to cancer care. There is an imminent need to understand and address access to cancer care and palliative care to reduce disparities within this population.
Methods
We interviewed 15 clinicians including physicians, nurses, nurse practitioners, social workers, and clinical psychologists specializing in primary care, palliative care, and oncology, self-identifying as White, Asian American, NHPI, and Multiracial. Interviews were transcribed verbatim and de-identified. Using inductive and deductive strategies, we iteratively collapsed content into codes formulating a codebook. Thematic analyses were performed using dual-coder review in Atlas.ti v23. Themes were mapped to the socioecological model.
Results
Clinicians described how NHPI/USAPI Veterans receive healthcare and instrumental support at individual, community, and systems levels, including from family caregivers, “high-talking chiefs,” traditional healers (“suruhanu”), community health clinics, and the VHA. Clinicians identified challenges and opportunities for care coordination: (1) financial and logistical barriers to involve family and decision-makers; (2) clinician understanding of cultural values and influence on medical decision-making; (3) care fragmentation resulting from transitions between community care and VHA; and (4) collaboration with key individuals in Pacific social hierarchies.
Conclusions
Cancer navigation and care coordination gaps create challenges for clinicians and NHPI/USAPI Veterans managing cancer in the Pacific Islands. Better understanding of these systems of care and associated gaps can inform the development of an intervention to improve cancer care delivery to this population. NHPI/ USAPI Veterans may experience care fragmentation due to care transitions between community care and the VHA. At the same time, these sources also create multiple layers of support for Veterans. Interventions to address these challenges can leverage the strengths of Pacific communities, while striving to better integrate care between community healthcare providers and VHA.
Background
The Palliative Care in Hawaii/Pacific Island Communities for Veterans (PaCiHPIC Veterans) study is a VA-funded research study that explores social determinants of health, cultural values, and cancer disparities impacting Native Hawaiian/Pacific Islander/US-affiliated Pacific Island resident (NHPI/USAPI) Veterans.Cancer prevalence and mortality are increasing among NHPI/ USAPI Veterans which can be partly attributed to nuclear fallout from U.S. military activities in the region. This population faces geographic, financial, and logistical barriers to cancer care. There is an imminent need to understand and address access to cancer care and palliative care to reduce disparities within this population.
Methods
We interviewed 15 clinicians including physicians, nurses, nurse practitioners, social workers, and clinical psychologists specializing in primary care, palliative care, and oncology, self-identifying as White, Asian American, NHPI, and Multiracial. Interviews were transcribed verbatim and de-identified. Using inductive and deductive strategies, we iteratively collapsed content into codes formulating a codebook. Thematic analyses were performed using dual-coder review in Atlas.ti v23. Themes were mapped to the socioecological model.
Results
Clinicians described how NHPI/USAPI Veterans receive healthcare and instrumental support at individual, community, and systems levels, including from family caregivers, “high-talking chiefs,” traditional healers (“suruhanu”), community health clinics, and the VHA. Clinicians identified challenges and opportunities for care coordination: (1) financial and logistical barriers to involve family and decision-makers; (2) clinician understanding of cultural values and influence on medical decision-making; (3) care fragmentation resulting from transitions between community care and VHA; and (4) collaboration with key individuals in Pacific social hierarchies.
Conclusions
Cancer navigation and care coordination gaps create challenges for clinicians and NHPI/USAPI Veterans managing cancer in the Pacific Islands. Better understanding of these systems of care and associated gaps can inform the development of an intervention to improve cancer care delivery to this population. NHPI/ USAPI Veterans may experience care fragmentation due to care transitions between community care and the VHA. At the same time, these sources also create multiple layers of support for Veterans. Interventions to address these challenges can leverage the strengths of Pacific communities, while striving to better integrate care between community healthcare providers and VHA.
Preleukemic Chronic Myeloid Leukemia: A Case Report and Literature Review
Background
CML is usually classified in chronic phase (CP), accelerated phase (AP) and/or Blast phase (BP). Studies have described another provisional entity as Preleukemic phase of CML which precedes CP and is without leukocytosis and blood features of CP phase of CML. Here we will present a case of metastatic prostate cancer, where next-generation sequencing showed BCR-ABL1 but no overt leukocytosis and then later developed clinical CML after 11 months.
Case Presentation
Our patient was 87-yr-old male with history of metastatic prostate cancer, who presented with elevated PSA levels and new bony metastasis. He underwent next-generation-sequencing (foundation one liquid cdx) in April 2022. It did not show reportable alterations related to prostate cancer but BCR-ABL1 (p210) fusion was detected. It also showed ASXL1-S846fs5 and TET2-Q1548 that are also markers of clonal hematopoiesis. In March 2023 (11 months after the finding of BCR-ABL1), he developed asymptomatic leukocytosis, Workup showed BCR-ABL1(210) of 44% in peripheral blood and bone marrow showed 9% blasts. He was started on Imatinib after shared decision-making and considering the toxicity profile and comorbidities. He followed up regularly with improvement in leukocytosis.
Discussion
The diagnosis of CML is first suspected by typical findings in blood and/or bone marrow and then confirmed by presence of Philadelphia chromosome. Along with chronic and accelerated phases, there is another term described in few cases called “preleukemic or smoldering or aleukemic phase.” This is not a wellestablished term but mostly defined as normal leukocyte count with presence of BCR/ABL1 fusion gene/ ph chromosome. Preleukemic phase of CML is mostly underdiagnosed or misdiagnosed. Our case is unique in that BCR/ABL1 fusion was detected incidentally on next-generation sequencing and patient progressed to chronic phase of CML 11 months later. Upon literature review, few case reports and case series documenting aleukemic/preleukemic phase of CML but timing from the appearance of BCR/ABL1 mutation to actual development to leukocytosis is not well documented. Especially in the era of NGS testing, patients with incidental BCR-ABL1 should be evaluated further irrespective of normal WBC. Further studies need to be done to recognize this early and decrease the delay in treatment.
Background
CML is usually classified in chronic phase (CP), accelerated phase (AP) and/or Blast phase (BP). Studies have described another provisional entity as Preleukemic phase of CML which precedes CP and is without leukocytosis and blood features of CP phase of CML. Here we will present a case of metastatic prostate cancer, where next-generation sequencing showed BCR-ABL1 but no overt leukocytosis and then later developed clinical CML after 11 months.
Case Presentation
Our patient was 87-yr-old male with history of metastatic prostate cancer, who presented with elevated PSA levels and new bony metastasis. He underwent next-generation-sequencing (foundation one liquid cdx) in April 2022. It did not show reportable alterations related to prostate cancer but BCR-ABL1 (p210) fusion was detected. It also showed ASXL1-S846fs5 and TET2-Q1548 that are also markers of clonal hematopoiesis. In March 2023 (11 months after the finding of BCR-ABL1), he developed asymptomatic leukocytosis, Workup showed BCR-ABL1(210) of 44% in peripheral blood and bone marrow showed 9% blasts. He was started on Imatinib after shared decision-making and considering the toxicity profile and comorbidities. He followed up regularly with improvement in leukocytosis.
Discussion
The diagnosis of CML is first suspected by typical findings in blood and/or bone marrow and then confirmed by presence of Philadelphia chromosome. Along with chronic and accelerated phases, there is another term described in few cases called “preleukemic or smoldering or aleukemic phase.” This is not a wellestablished term but mostly defined as normal leukocyte count with presence of BCR/ABL1 fusion gene/ ph chromosome. Preleukemic phase of CML is mostly underdiagnosed or misdiagnosed. Our case is unique in that BCR/ABL1 fusion was detected incidentally on next-generation sequencing and patient progressed to chronic phase of CML 11 months later. Upon literature review, few case reports and case series documenting aleukemic/preleukemic phase of CML but timing from the appearance of BCR/ABL1 mutation to actual development to leukocytosis is not well documented. Especially in the era of NGS testing, patients with incidental BCR-ABL1 should be evaluated further irrespective of normal WBC. Further studies need to be done to recognize this early and decrease the delay in treatment.
Background
CML is usually classified in chronic phase (CP), accelerated phase (AP) and/or Blast phase (BP). Studies have described another provisional entity as Preleukemic phase of CML which precedes CP and is without leukocytosis and blood features of CP phase of CML. Here we will present a case of metastatic prostate cancer, where next-generation sequencing showed BCR-ABL1 but no overt leukocytosis and then later developed clinical CML after 11 months.
Case Presentation
Our patient was 87-yr-old male with history of metastatic prostate cancer, who presented with elevated PSA levels and new bony metastasis. He underwent next-generation-sequencing (foundation one liquid cdx) in April 2022. It did not show reportable alterations related to prostate cancer but BCR-ABL1 (p210) fusion was detected. It also showed ASXL1-S846fs5 and TET2-Q1548 that are also markers of clonal hematopoiesis. In March 2023 (11 months after the finding of BCR-ABL1), he developed asymptomatic leukocytosis, Workup showed BCR-ABL1(210) of 44% in peripheral blood and bone marrow showed 9% blasts. He was started on Imatinib after shared decision-making and considering the toxicity profile and comorbidities. He followed up regularly with improvement in leukocytosis.
Discussion
The diagnosis of CML is first suspected by typical findings in blood and/or bone marrow and then confirmed by presence of Philadelphia chromosome. Along with chronic and accelerated phases, there is another term described in few cases called “preleukemic or smoldering or aleukemic phase.” This is not a wellestablished term but mostly defined as normal leukocyte count with presence of BCR/ABL1 fusion gene/ ph chromosome. Preleukemic phase of CML is mostly underdiagnosed or misdiagnosed. Our case is unique in that BCR/ABL1 fusion was detected incidentally on next-generation sequencing and patient progressed to chronic phase of CML 11 months later. Upon literature review, few case reports and case series documenting aleukemic/preleukemic phase of CML but timing from the appearance of BCR/ABL1 mutation to actual development to leukocytosis is not well documented. Especially in the era of NGS testing, patients with incidental BCR-ABL1 should be evaluated further irrespective of normal WBC. Further studies need to be done to recognize this early and decrease the delay in treatment.
Influence of Patient Demographics and Facility Type on Overall Survival in Sezary Syndrome
Background
This study investigates the effects of patient characteristics on overall survival in Sezary Syndrome (SS), addressing a gap in the current literature. SS is a rare and aggressive form of cutaneous T-cell lymphoma (CTCL). SS is presumed to be related to service exposure, and veterans have a 6-8 times higher incidence of CTCL than the general population. A study investigating the socio-demographic factors at diagnosis on overall survival in SS has yet to be done.
Methods
This is a retrospective study of patients diagnosed with SS (ICD- 9701/3) between 2004 and 2020 in the National Cancer Database (NCDB), highlighting patient demographics on overall survival in SS (N = 809). Exclusion criteria included missing data. Descriptive statistics were collected for all patients with SS. Overall survival was determined via KaplanMeier test. Multivariate analysis via Cox regression was performed to determine factors leading to decreased survival in SS. All statistical tests were evaluated for a significance of P < 0.05.
Results
Of 809 patients with SS, the majority were White (77.3%), male (57.8%), and had an average age at diagnosis of 66.9 years (SD=13.0). Age at diagnosis was associated with decreased overall survival (HR 0.028; 95% CI, 1.016 – 1.042, P< 0.05). Patients with SS treated at nonacademic facilities had a HR of 0.41 (95% CI, 1.171 – 1.932, P< 0.05) compared to academic facilities. Those with private insurance had improved survival with a HR of -0.83 [95% CI, (-0.241) - (-0.781), P< 0.05] compared to those who were non-insured. The average survival time for patients with SS was found to be 73.1 months. The average survival time for patients treated at academic facilities was 8.8 months longer than those treated at nonacademic facilities (75.0 vs 66.2 months, P< 0.05). Patients with private insurance had higher overall survival compared to government-insured and non-insured patients (100.4 versus 56.9 and 54.2 months, respectively). Age, facility type, and primary payor are significant factors that affect survival in SS. Further studies should address the influence of these factors on treatments received by SS patients to decrease disparity related to care.
Background
This study investigates the effects of patient characteristics on overall survival in Sezary Syndrome (SS), addressing a gap in the current literature. SS is a rare and aggressive form of cutaneous T-cell lymphoma (CTCL). SS is presumed to be related to service exposure, and veterans have a 6-8 times higher incidence of CTCL than the general population. A study investigating the socio-demographic factors at diagnosis on overall survival in SS has yet to be done.
Methods
This is a retrospective study of patients diagnosed with SS (ICD- 9701/3) between 2004 and 2020 in the National Cancer Database (NCDB), highlighting patient demographics on overall survival in SS (N = 809). Exclusion criteria included missing data. Descriptive statistics were collected for all patients with SS. Overall survival was determined via KaplanMeier test. Multivariate analysis via Cox regression was performed to determine factors leading to decreased survival in SS. All statistical tests were evaluated for a significance of P < 0.05.
Results
Of 809 patients with SS, the majority were White (77.3%), male (57.8%), and had an average age at diagnosis of 66.9 years (SD=13.0). Age at diagnosis was associated with decreased overall survival (HR 0.028; 95% CI, 1.016 – 1.042, P< 0.05). Patients with SS treated at nonacademic facilities had a HR of 0.41 (95% CI, 1.171 – 1.932, P< 0.05) compared to academic facilities. Those with private insurance had improved survival with a HR of -0.83 [95% CI, (-0.241) - (-0.781), P< 0.05] compared to those who were non-insured. The average survival time for patients with SS was found to be 73.1 months. The average survival time for patients treated at academic facilities was 8.8 months longer than those treated at nonacademic facilities (75.0 vs 66.2 months, P< 0.05). Patients with private insurance had higher overall survival compared to government-insured and non-insured patients (100.4 versus 56.9 and 54.2 months, respectively). Age, facility type, and primary payor are significant factors that affect survival in SS. Further studies should address the influence of these factors on treatments received by SS patients to decrease disparity related to care.
Background
This study investigates the effects of patient characteristics on overall survival in Sezary Syndrome (SS), addressing a gap in the current literature. SS is a rare and aggressive form of cutaneous T-cell lymphoma (CTCL). SS is presumed to be related to service exposure, and veterans have a 6-8 times higher incidence of CTCL than the general population. A study investigating the socio-demographic factors at diagnosis on overall survival in SS has yet to be done.
Methods
This is a retrospective study of patients diagnosed with SS (ICD- 9701/3) between 2004 and 2020 in the National Cancer Database (NCDB), highlighting patient demographics on overall survival in SS (N = 809). Exclusion criteria included missing data. Descriptive statistics were collected for all patients with SS. Overall survival was determined via KaplanMeier test. Multivariate analysis via Cox regression was performed to determine factors leading to decreased survival in SS. All statistical tests were evaluated for a significance of P < 0.05.
Results
Of 809 patients with SS, the majority were White (77.3%), male (57.8%), and had an average age at diagnosis of 66.9 years (SD=13.0). Age at diagnosis was associated with decreased overall survival (HR 0.028; 95% CI, 1.016 – 1.042, P< 0.05). Patients with SS treated at nonacademic facilities had a HR of 0.41 (95% CI, 1.171 – 1.932, P< 0.05) compared to academic facilities. Those with private insurance had improved survival with a HR of -0.83 [95% CI, (-0.241) - (-0.781), P< 0.05] compared to those who were non-insured. The average survival time for patients with SS was found to be 73.1 months. The average survival time for patients treated at academic facilities was 8.8 months longer than those treated at nonacademic facilities (75.0 vs 66.2 months, P< 0.05). Patients with private insurance had higher overall survival compared to government-insured and non-insured patients (100.4 versus 56.9 and 54.2 months, respectively). Age, facility type, and primary payor are significant factors that affect survival in SS. Further studies should address the influence of these factors on treatments received by SS patients to decrease disparity related to care.
RVD With Weekly Bortezomib Has a Favorable Toxicity and Effectiveness Profile in a Large Cohort of US Veterans With Multiple Myeloma
Background
Lenalidomide, bortezomib, and dexamethasone (RVD) is standard triplet induction for fit newly-diagnosed myeloma (NDMM) patients, with response rate (RR)>90%. A 21-day cycle with bortezomib given days 1, 4, 8, and 11 (2x/w) is standard. However, up to 80% of patients develop neuropathy. Weekly bortezomib dosing (1x/w), subcutaneous route, and 28- to 35-day cycle length may optimize tolerance. We present an effectiveness and toxicity analysis of Veterans who received RVD with 1x/w and 2x/w bortezomib for NDMM.
Methods
The VA Corporate Data Warehouse identified 1499 Veterans with NDMM given RVD ≤42 days of treatment start. 840 Veterans were grouped for initial analysis based on criteria: 1) lenalidomide and ≥ 3 bortezomib doses during cycle 1; 2) ≥6 mean days between bortezomib treatments=1x/w); and 3) number of lenalidomide days informed cycle length (21d, 28d, or 35d; default 7-day rest). Investigators reviewed algorithm results to finalize group assignments. Endpoints included depth of response, time to next treatment (TTNT), overall survival (OS), and neuropathy. Neuropathy was defined as use of neuropathy medications and neuropathy ICD-10 codes.
Results
Our algorithm correctly assigned 82% of 840 cycle 1 RVD schedules. The largest groups were 21d 1x/w (n=291), 21d 2x/w (n=193), 28d 1x/w (n=188), and 28d 2x/w (n=82). Median age was 68.3; 53% were non-Hispanic White. Demographics and ISS stage of groups were similar. 30% underwent autologous transplant. Tolerability. Median number of bortezomib doses ranged from 22.5-25.5 (p=0.57). Neuropathy favored 1x/w, 17.7 vs 30.2% (p=0.0001) and was highest (34.7%) in 21d 2x/w. Effectiveness. Response was assessable for 28% of patients. RR (72%, p=0.68) and median TTNT (19.3 months, p=0.20) were similar, including 1x/w vs 2x/w comparison (p=0.79). 21d regimens optimized TTNT (21.4 vs 13.9 months, p=0.045) and trended to better OS (73 vs 65 months, p=0.06).
Conclusions
1x/w RVD preserved effectiveness compared to “standard” RVD in a large Veteran cohort. 1x/w reduced neuropathy incidence. 28d regimens demonstrated inferior longer-term outcomes. Certain endpoints, such as RR and neuropathy, appear underestimated due to data source limitations. 21d 1x/w RVD optimizes effectiveness, tolerability, and administration and should be considered for broader utilization in Veterans with NDMM.
Background
Lenalidomide, bortezomib, and dexamethasone (RVD) is standard triplet induction for fit newly-diagnosed myeloma (NDMM) patients, with response rate (RR)>90%. A 21-day cycle with bortezomib given days 1, 4, 8, and 11 (2x/w) is standard. However, up to 80% of patients develop neuropathy. Weekly bortezomib dosing (1x/w), subcutaneous route, and 28- to 35-day cycle length may optimize tolerance. We present an effectiveness and toxicity analysis of Veterans who received RVD with 1x/w and 2x/w bortezomib for NDMM.
Methods
The VA Corporate Data Warehouse identified 1499 Veterans with NDMM given RVD ≤42 days of treatment start. 840 Veterans were grouped for initial analysis based on criteria: 1) lenalidomide and ≥ 3 bortezomib doses during cycle 1; 2) ≥6 mean days between bortezomib treatments=1x/w); and 3) number of lenalidomide days informed cycle length (21d, 28d, or 35d; default 7-day rest). Investigators reviewed algorithm results to finalize group assignments. Endpoints included depth of response, time to next treatment (TTNT), overall survival (OS), and neuropathy. Neuropathy was defined as use of neuropathy medications and neuropathy ICD-10 codes.
Results
Our algorithm correctly assigned 82% of 840 cycle 1 RVD schedules. The largest groups were 21d 1x/w (n=291), 21d 2x/w (n=193), 28d 1x/w (n=188), and 28d 2x/w (n=82). Median age was 68.3; 53% were non-Hispanic White. Demographics and ISS stage of groups were similar. 30% underwent autologous transplant. Tolerability. Median number of bortezomib doses ranged from 22.5-25.5 (p=0.57). Neuropathy favored 1x/w, 17.7 vs 30.2% (p=0.0001) and was highest (34.7%) in 21d 2x/w. Effectiveness. Response was assessable for 28% of patients. RR (72%, p=0.68) and median TTNT (19.3 months, p=0.20) were similar, including 1x/w vs 2x/w comparison (p=0.79). 21d regimens optimized TTNT (21.4 vs 13.9 months, p=0.045) and trended to better OS (73 vs 65 months, p=0.06).
Conclusions
1x/w RVD preserved effectiveness compared to “standard” RVD in a large Veteran cohort. 1x/w reduced neuropathy incidence. 28d regimens demonstrated inferior longer-term outcomes. Certain endpoints, such as RR and neuropathy, appear underestimated due to data source limitations. 21d 1x/w RVD optimizes effectiveness, tolerability, and administration and should be considered for broader utilization in Veterans with NDMM.
Background
Lenalidomide, bortezomib, and dexamethasone (RVD) is standard triplet induction for fit newly-diagnosed myeloma (NDMM) patients, with response rate (RR)>90%. A 21-day cycle with bortezomib given days 1, 4, 8, and 11 (2x/w) is standard. However, up to 80% of patients develop neuropathy. Weekly bortezomib dosing (1x/w), subcutaneous route, and 28- to 35-day cycle length may optimize tolerance. We present an effectiveness and toxicity analysis of Veterans who received RVD with 1x/w and 2x/w bortezomib for NDMM.
Methods
The VA Corporate Data Warehouse identified 1499 Veterans with NDMM given RVD ≤42 days of treatment start. 840 Veterans were grouped for initial analysis based on criteria: 1) lenalidomide and ≥ 3 bortezomib doses during cycle 1; 2) ≥6 mean days between bortezomib treatments=1x/w); and 3) number of lenalidomide days informed cycle length (21d, 28d, or 35d; default 7-day rest). Investigators reviewed algorithm results to finalize group assignments. Endpoints included depth of response, time to next treatment (TTNT), overall survival (OS), and neuropathy. Neuropathy was defined as use of neuropathy medications and neuropathy ICD-10 codes.
Results
Our algorithm correctly assigned 82% of 840 cycle 1 RVD schedules. The largest groups were 21d 1x/w (n=291), 21d 2x/w (n=193), 28d 1x/w (n=188), and 28d 2x/w (n=82). Median age was 68.3; 53% were non-Hispanic White. Demographics and ISS stage of groups were similar. 30% underwent autologous transplant. Tolerability. Median number of bortezomib doses ranged from 22.5-25.5 (p=0.57). Neuropathy favored 1x/w, 17.7 vs 30.2% (p=0.0001) and was highest (34.7%) in 21d 2x/w. Effectiveness. Response was assessable for 28% of patients. RR (72%, p=0.68) and median TTNT (19.3 months, p=0.20) were similar, including 1x/w vs 2x/w comparison (p=0.79). 21d regimens optimized TTNT (21.4 vs 13.9 months, p=0.045) and trended to better OS (73 vs 65 months, p=0.06).
Conclusions
1x/w RVD preserved effectiveness compared to “standard” RVD in a large Veteran cohort. 1x/w reduced neuropathy incidence. 28d regimens demonstrated inferior longer-term outcomes. Certain endpoints, such as RR and neuropathy, appear underestimated due to data source limitations. 21d 1x/w RVD optimizes effectiveness, tolerability, and administration and should be considered for broader utilization in Veterans with NDMM.
Male Patient With a History of Monoclonal B Cell Lymphocytosis Presenting with Breast Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report and Literature Review
Background
Monoclonal B cell lymphocytosis (MBL) is defined as presence of clonal b cell population that is fewer than 5 × 10(9)/L B-cells in peripheral blood and no other signs of a lymphoproliferative disorder. Patients with MBL are usually monitored with periodic history, physical exam and blood counts. Here we presented a case of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in breast in a patient with a history of MBL.
Case Presentation
68-year-old male with history of MBL underwent mammogram for breast mass. It showed suspicious 4.4 x 1.6 cm solid and cystic lesion containing a 1.7 x 0.9 x 1.8 cm solid hypervascular mass. Patient underwent left breast mass excision. Histologic sections focus of ADH involving papilloma with uninvolved margins. Lymphoid infiltrates noted had CLL/SLL immunophenotype and that it consists mostly of small B cells positive for CD5, CD20, CD23, CD43, Bcl-2, LEF1. CT CAP and PET/CT were negative for lymphadenopathy. Bone marrow biopsy showed marrow involvement by mature B-cell lymphoproliferative process, immunophenotypically consistent with CLL/SLL. As intra-ductal papilloma completely excised and hemogram was normal tumor board recommended surveillance only for CLL/SLL.
Discussion
MBL can progress to CLL, but it can rarely be presented as an extra-nodal mass in solid organs. We described a case of MBL that progressed to CLL/ SLL in breast mass in a male patient. This is the first reported case in literature where MBL progressed to CLL/ SLL of breast without lymphadenopathy. Upon literature review 8 case reports were found where CLL/SLL were described in breast tissue. 7 of them were in females and 1 one was in male. Two patients had CLL before breast mass but none of them had a history of MBL. 3 described cases in females had CLL/SLL infiltration of breast along with invasive ductal carcinoma. So, a patient with MBL can progress to involve solid organs despite no absolute lymphocytosis and should be considered in differentials of a new mass. Although more common in females, but it can occur in males as well. It’s important to consider the possibility of both CLL/SLL and breast cancer existing simultaneously.
Background
Monoclonal B cell lymphocytosis (MBL) is defined as presence of clonal b cell population that is fewer than 5 × 10(9)/L B-cells in peripheral blood and no other signs of a lymphoproliferative disorder. Patients with MBL are usually monitored with periodic history, physical exam and blood counts. Here we presented a case of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in breast in a patient with a history of MBL.
Case Presentation
68-year-old male with history of MBL underwent mammogram for breast mass. It showed suspicious 4.4 x 1.6 cm solid and cystic lesion containing a 1.7 x 0.9 x 1.8 cm solid hypervascular mass. Patient underwent left breast mass excision. Histologic sections focus of ADH involving papilloma with uninvolved margins. Lymphoid infiltrates noted had CLL/SLL immunophenotype and that it consists mostly of small B cells positive for CD5, CD20, CD23, CD43, Bcl-2, LEF1. CT CAP and PET/CT were negative for lymphadenopathy. Bone marrow biopsy showed marrow involvement by mature B-cell lymphoproliferative process, immunophenotypically consistent with CLL/SLL. As intra-ductal papilloma completely excised and hemogram was normal tumor board recommended surveillance only for CLL/SLL.
Discussion
MBL can progress to CLL, but it can rarely be presented as an extra-nodal mass in solid organs. We described a case of MBL that progressed to CLL/ SLL in breast mass in a male patient. This is the first reported case in literature where MBL progressed to CLL/ SLL of breast without lymphadenopathy. Upon literature review 8 case reports were found where CLL/SLL were described in breast tissue. 7 of them were in females and 1 one was in male. Two patients had CLL before breast mass but none of them had a history of MBL. 3 described cases in females had CLL/SLL infiltration of breast along with invasive ductal carcinoma. So, a patient with MBL can progress to involve solid organs despite no absolute lymphocytosis and should be considered in differentials of a new mass. Although more common in females, but it can occur in males as well. It’s important to consider the possibility of both CLL/SLL and breast cancer existing simultaneously.
Background
Monoclonal B cell lymphocytosis (MBL) is defined as presence of clonal b cell population that is fewer than 5 × 10(9)/L B-cells in peripheral blood and no other signs of a lymphoproliferative disorder. Patients with MBL are usually monitored with periodic history, physical exam and blood counts. Here we presented a case of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in breast in a patient with a history of MBL.
Case Presentation
68-year-old male with history of MBL underwent mammogram for breast mass. It showed suspicious 4.4 x 1.6 cm solid and cystic lesion containing a 1.7 x 0.9 x 1.8 cm solid hypervascular mass. Patient underwent left breast mass excision. Histologic sections focus of ADH involving papilloma with uninvolved margins. Lymphoid infiltrates noted had CLL/SLL immunophenotype and that it consists mostly of small B cells positive for CD5, CD20, CD23, CD43, Bcl-2, LEF1. CT CAP and PET/CT were negative for lymphadenopathy. Bone marrow biopsy showed marrow involvement by mature B-cell lymphoproliferative process, immunophenotypically consistent with CLL/SLL. As intra-ductal papilloma completely excised and hemogram was normal tumor board recommended surveillance only for CLL/SLL.
Discussion
MBL can progress to CLL, but it can rarely be presented as an extra-nodal mass in solid organs. We described a case of MBL that progressed to CLL/ SLL in breast mass in a male patient. This is the first reported case in literature where MBL progressed to CLL/ SLL of breast without lymphadenopathy. Upon literature review 8 case reports were found where CLL/SLL were described in breast tissue. 7 of them were in females and 1 one was in male. Two patients had CLL before breast mass but none of them had a history of MBL. 3 described cases in females had CLL/SLL infiltration of breast along with invasive ductal carcinoma. So, a patient with MBL can progress to involve solid organs despite no absolute lymphocytosis and should be considered in differentials of a new mass. Although more common in females, but it can occur in males as well. It’s important to consider the possibility of both CLL/SLL and breast cancer existing simultaneously.
Chronic Myeloid Leukemia Presenting as Priapism: A Rare and Acute Initial Presentation in a Young Male
Introduction
Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).
Case Presentation
A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.
Discussion
Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.
Introduction
Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).
Case Presentation
A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.
Discussion
Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.
Introduction
Priapism, defined as a prolonged and often painful penile erection without sexual arousal, constitutes a urological emergency requiring immediate intervention. While commonly associated with conditions like sickle cell anemia and certain medications, malignancy-related priapism is rare and frequently overlooked. Herein, we present a unique case of a 31-year-old male with no significant medical history, who developed persistent priapism as the initial presentation of chronic myeloid leukemia (CML).
Case Presentation
A 31-year-old male without significant medical history, presented to the emergency department with painless priapism, was evaluated by urology and discharged home with precautions. He returned the following day with persistent, now painful priapism. Upon examination, his vital signs were stable. Urology performed aspiration and injection with Sudafed, resulting in mild symptom improvement. Laboratory findings revealed elevated white blood cell count (563.64 k/mcL), anemia (hemoglobin 8.4 g/dL), and a peripheral blood smear showed immature circulating cells with blast forms. He was transferred to a tertiary care center where conservative management addressed bleeding from the penile injection site, with subsequent treatment including leukapheresis and hydroxyurea for cytoreduction. Imaging revealed severe splenomegaly (36 cm) with abdominal mass effect. Peripheral flow cytometry didn’t show malignancy, but cytogenetic analysis showed a BCR/ABL1 fusion gene, confirming chronic myeloid leukemia (CML). Bone marrow biopsy showed hypercellularity without increased blasts. Treatment with dasatinib reduced the white count to 52,000 k/mcL, and was discharged home.
Discussion
Priapism is a urological emergency necessitating immediate intervention to prevent erectile dysfunction and permanent impotence. Management aims to achieve detumescence and typically involves methods such as irrigation or injection of vasoconstrictors into the penis. Malignancy-associated priapism (MAP) often results from venous obstruction due to hyperviscosity. Studies show that CML accounts for approximately 50% cases presenting with MAP, predominantly affecting younger individuals with a mean onset around 27 years of age. Priapism can occur before, during, or after treatment initiation or splenectomy in these patients. Providers should keep a high threshold of suspicion for MAP in patients with no other risk factors as prompt identification and treatment are needed to avoid permanent injury.
Agent Orange and Myelodysplastic Syndrome: A Single VAMC Experience
Background
Agent Orange (AO) exposure may be linked to development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.
Methods
All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR (CPRS) and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).
Results
129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.
Conclusions
This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML.
Background
Agent Orange (AO) exposure may be linked to development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.
Methods
All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR (CPRS) and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).
Results
129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.
Conclusions
This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML.
Background
Agent Orange (AO) exposure may be linked to development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.
Methods
All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR (CPRS) and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).
Results
129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.
Conclusions
This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML.
UC as a Culprit for Hemolytic Anemia
Introduction
Autoimmune hemolytic anemia (AIHA) can rarely be seen as an extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD), mostly ulcerative colitis (UC). This case report describes the clinical significance of recognizing AIHA in the context of UC.
Case Presentation
A 32-year-old male presented with profound fatigue, pallor, and dyspnea on exertion for one month. He also recalled intermittent bloody diarrhea for two years for which he never sought medical attention. Physical examination was unremarkable except for mid-abdominal tenderness. Labs revealed microcytosis, hemoglobin of 3.8 g/dL, total bilirubin 2.9 mg/ dL, indirect bilirubin of 2.0 mg/dL, LDH 132 U/L alk-p 459 U/L AST 98 U/L ALT 22 U/L. Direct Coombs test was positive suggesting warm AIHA with pan-agglutinin positive on the eluate test. Further testing revealed negative hepatitis and HIV panels and positive fecal calprotectin. CT abdomen and pelvis showed ascites, right pleural effusion and hepatosplenomegaly. Colonoscopy confirmed the diagnosis of ulcerative colitis, with extensive involvement of the colon. Mesalamine was initiated. Hematology was consulted for AIHA, who started the patient on methylprednisone leading to resolution of hemolytic anemia and improvement in gastrointestinal symptoms.
Discussion
IBD typically manifests as colitis, and the incidence of EIM as an initial symptom is observed in less than 10% cases. However, over the course of their lifetime, approximately 25% of patients will experience EIM, underscoring their relevance to clinical outcomes. Anemia is very common in IBD patients, mostly iron deficiency anemia (IDA) or anemia of chronic disease (ACD). However, AIHA can represent a rare but significant EIM of ulcerative colitis (UC), often posing diagnostic challenges. The underlying pathophysiological mechanisms linking UC and AIHA remain incompletely understood, necessitating a multidisciplinary approach to management. Treatment strategies focus on controlling both the hemolysis and the underlying IBD, emphasizing the importance of tailored interventions.
Conclusion
This case underscores the clinical significance of AIHA as an EIM of ulcerative colitis (UC), particularly when presenting as the primary symptom. Timely recognition is paramount to optimizing patient outcomes and preventing disease progression. Further research is warranted to elucidate the underlying mechanisms and therapeutic strategies for AIHA in the context of UC.
Introduction
Autoimmune hemolytic anemia (AIHA) can rarely be seen as an extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD), mostly ulcerative colitis (UC). This case report describes the clinical significance of recognizing AIHA in the context of UC.
Case Presentation
A 32-year-old male presented with profound fatigue, pallor, and dyspnea on exertion for one month. He also recalled intermittent bloody diarrhea for two years for which he never sought medical attention. Physical examination was unremarkable except for mid-abdominal tenderness. Labs revealed microcytosis, hemoglobin of 3.8 g/dL, total bilirubin 2.9 mg/ dL, indirect bilirubin of 2.0 mg/dL, LDH 132 U/L alk-p 459 U/L AST 98 U/L ALT 22 U/L. Direct Coombs test was positive suggesting warm AIHA with pan-agglutinin positive on the eluate test. Further testing revealed negative hepatitis and HIV panels and positive fecal calprotectin. CT abdomen and pelvis showed ascites, right pleural effusion and hepatosplenomegaly. Colonoscopy confirmed the diagnosis of ulcerative colitis, with extensive involvement of the colon. Mesalamine was initiated. Hematology was consulted for AIHA, who started the patient on methylprednisone leading to resolution of hemolytic anemia and improvement in gastrointestinal symptoms.
Discussion
IBD typically manifests as colitis, and the incidence of EIM as an initial symptom is observed in less than 10% cases. However, over the course of their lifetime, approximately 25% of patients will experience EIM, underscoring their relevance to clinical outcomes. Anemia is very common in IBD patients, mostly iron deficiency anemia (IDA) or anemia of chronic disease (ACD). However, AIHA can represent a rare but significant EIM of ulcerative colitis (UC), often posing diagnostic challenges. The underlying pathophysiological mechanisms linking UC and AIHA remain incompletely understood, necessitating a multidisciplinary approach to management. Treatment strategies focus on controlling both the hemolysis and the underlying IBD, emphasizing the importance of tailored interventions.
Conclusion
This case underscores the clinical significance of AIHA as an EIM of ulcerative colitis (UC), particularly when presenting as the primary symptom. Timely recognition is paramount to optimizing patient outcomes and preventing disease progression. Further research is warranted to elucidate the underlying mechanisms and therapeutic strategies for AIHA in the context of UC.
Introduction
Autoimmune hemolytic anemia (AIHA) can rarely be seen as an extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD), mostly ulcerative colitis (UC). This case report describes the clinical significance of recognizing AIHA in the context of UC.
Case Presentation
A 32-year-old male presented with profound fatigue, pallor, and dyspnea on exertion for one month. He also recalled intermittent bloody diarrhea for two years for which he never sought medical attention. Physical examination was unremarkable except for mid-abdominal tenderness. Labs revealed microcytosis, hemoglobin of 3.8 g/dL, total bilirubin 2.9 mg/ dL, indirect bilirubin of 2.0 mg/dL, LDH 132 U/L alk-p 459 U/L AST 98 U/L ALT 22 U/L. Direct Coombs test was positive suggesting warm AIHA with pan-agglutinin positive on the eluate test. Further testing revealed negative hepatitis and HIV panels and positive fecal calprotectin. CT abdomen and pelvis showed ascites, right pleural effusion and hepatosplenomegaly. Colonoscopy confirmed the diagnosis of ulcerative colitis, with extensive involvement of the colon. Mesalamine was initiated. Hematology was consulted for AIHA, who started the patient on methylprednisone leading to resolution of hemolytic anemia and improvement in gastrointestinal symptoms.
Discussion
IBD typically manifests as colitis, and the incidence of EIM as an initial symptom is observed in less than 10% cases. However, over the course of their lifetime, approximately 25% of patients will experience EIM, underscoring their relevance to clinical outcomes. Anemia is very common in IBD patients, mostly iron deficiency anemia (IDA) or anemia of chronic disease (ACD). However, AIHA can represent a rare but significant EIM of ulcerative colitis (UC), often posing diagnostic challenges. The underlying pathophysiological mechanisms linking UC and AIHA remain incompletely understood, necessitating a multidisciplinary approach to management. Treatment strategies focus on controlling both the hemolysis and the underlying IBD, emphasizing the importance of tailored interventions.
Conclusion
This case underscores the clinical significance of AIHA as an EIM of ulcerative colitis (UC), particularly when presenting as the primary symptom. Timely recognition is paramount to optimizing patient outcomes and preventing disease progression. Further research is warranted to elucidate the underlying mechanisms and therapeutic strategies for AIHA in the context of UC.