Key clinical point: Higher pretransplant red blood cell (RBC) and platelet transfusion burden has an independent association with higher overall and relapse-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndrome (MDS).

Major finding: A higher pretransplant RBC transfusion burden was significantly associated with lower overall survival (OS; P less than .001) and higher relapse-related mortality (P less than .001). Similarly, a higher pretransplant platelet transfusion burden was associated with lower OS (P less than .001) and higher relapse-related mortality (P = .001).

Study details: A retrospective study examined the effects of pretransplant RBC and platelet transfusion burden on outcomes after allo-HSCT in 1,007 adults with de novo MDS.

Disclosures: This study was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development. The authors declared no conflicts of interest.

Source: Konuma T et al. Transplant Cell Ther. 2021 May 12. doi: 10.1016/j.jtct.2021.05.003.

Key clinical point: Higher pretransplant red blood cell (RBC) and platelet transfusion burden has an independent association with higher overall and relapse-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndrome (MDS).

Major finding: A higher pretransplant RBC transfusion burden was significantly associated with lower overall survival (OS; P less than .001) and higher relapse-related mortality (P less than .001). Similarly, a higher pretransplant platelet transfusion burden was associated with lower OS (P less than .001) and higher relapse-related mortality (P = .001).

Study details: A retrospective study examined the effects of pretransplant RBC and platelet transfusion burden on outcomes after allo-HSCT in 1,007 adults with de novo MDS.

Disclosures: This study was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development. The authors declared no conflicts of interest.

Source: Konuma T et al. Transplant Cell Ther. 2021 May 12. doi: 10.1016/j.jtct.2021.05.003.

Key clinical point: Higher pretransplant red blood cell (RBC) and platelet transfusion burden has an independent association with higher overall and relapse-related mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for de novo myelodysplastic syndrome (MDS).

Major finding: A higher pretransplant RBC transfusion burden was significantly associated with lower overall survival (OS; P less than .001) and higher relapse-related mortality (P less than .001). Similarly, a higher pretransplant platelet transfusion burden was associated with lower OS (P less than .001) and higher relapse-related mortality (P = .001).

Study details: A retrospective study examined the effects of pretransplant RBC and platelet transfusion burden on outcomes after allo-HSCT in 1,007 adults with de novo MDS.

Disclosures: This study was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development. The authors declared no conflicts of interest.

Source: Konuma T et al. Transplant Cell Ther. 2021 May 12. doi: 10.1016/j.jtct.2021.05.003.

Key clinical point: Less restrictive inclusion and exclusion criteria are warranted to improve the participation of patients with myelodysplastic syndrome (MDS) in clinical trials.

Major finding: Each trial was suitable for ~18% of patients in the cohort, whereas 34% of the patients were eligible for at least 1 of the 9 trials. Pharma-initiated trials excluded more than twice the fraction of patients vs. investigator-initiated trials (inclusion, 10% vs. 21%). Key reasons for exclusion included karyotype (average exclusion rate, 58%), comorbidities (40%), and previous therapies (55%)

Study details: A simulation exercise was performed to estimate the average proportion of MDS patients eligible for participation in a clinical trial. A total of 1,809 patients were included in the cohort.

Disclosures: This study did not receive any funding. K Nachtkamp, T Schroeder, E Schuler, J Kaivers, A Giagounidis, C Rautenberg, N Gattermann, and U Germing reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Nachtkamp K et al. Leuk Res. 2021 May 11. doi: 10.1016/j.leukres.2021.106611.

Key clinical point: Less restrictive inclusion and exclusion criteria are warranted to improve the participation of patients with myelodysplastic syndrome (MDS) in clinical trials.

Major finding: Each trial was suitable for ~18% of patients in the cohort, whereas 34% of the patients were eligible for at least 1 of the 9 trials. Pharma-initiated trials excluded more than twice the fraction of patients vs. investigator-initiated trials (inclusion, 10% vs. 21%). Key reasons for exclusion included karyotype (average exclusion rate, 58%), comorbidities (40%), and previous therapies (55%)

Study details: A simulation exercise was performed to estimate the average proportion of MDS patients eligible for participation in a clinical trial. A total of 1,809 patients were included in the cohort.

Disclosures: This study did not receive any funding. K Nachtkamp, T Schroeder, E Schuler, J Kaivers, A Giagounidis, C Rautenberg, N Gattermann, and U Germing reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Nachtkamp K et al. Leuk Res. 2021 May 11. doi: 10.1016/j.leukres.2021.106611.

Key clinical point: Less restrictive inclusion and exclusion criteria are warranted to improve the participation of patients with myelodysplastic syndrome (MDS) in clinical trials.

Major finding: Each trial was suitable for ~18% of patients in the cohort, whereas 34% of the patients were eligible for at least 1 of the 9 trials. Pharma-initiated trials excluded more than twice the fraction of patients vs. investigator-initiated trials (inclusion, 10% vs. 21%). Key reasons for exclusion included karyotype (average exclusion rate, 58%), comorbidities (40%), and previous therapies (55%)

Study details: A simulation exercise was performed to estimate the average proportion of MDS patients eligible for participation in a clinical trial. A total of 1,809 patients were included in the cohort.

Disclosures: This study did not receive any funding. K Nachtkamp, T Schroeder, E Schuler, J Kaivers, A Giagounidis, C Rautenberg, N Gattermann, and U Germing reported relationships with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Nachtkamp K et al. Leuk Res. 2021 May 11. doi: 10.1016/j.leukres.2021.106611.

Key clinical point: Inhibition of T cells by programmed death-ligand 1 (PD-L1)-expressing hematopoietic stem cells could be an underlying mechanism in the development of myelodysplastic syndrome (MDS). The findings support the potential use of immune checkpoint inhibitors in the treatment of suitable MDS patients.

Major finding: Significantly increased proportions of PD-L1⁺CD34⁺ stem cells were seen in MDS patients compared with hematopoietic stem cell transplantation (HSCT) recipients in remission for both the CD38⁻ subset (P = .0127) and CD38⁺ subset (P = .0336).

Study details: The study included 7 MDS and 9 acute myeloid leukemia samples. Six HSCT recipients who remained in remission for more than 6 months were considered controls.

Disclosures: The study was supported by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf). The authors declared no conflicts of interest.

Source: Moskorz W et al. Br J Haematol. 2021 May 6. doi: 10.1111/bjh.17461.

Key clinical point: Inhibition of T cells by programmed death-ligand 1 (PD-L1)-expressing hematopoietic stem cells could be an underlying mechanism in the development of myelodysplastic syndrome (MDS). The findings support the potential use of immune checkpoint inhibitors in the treatment of suitable MDS patients.

Major finding: Significantly increased proportions of PD-L1⁺CD34⁺ stem cells were seen in MDS patients compared with hematopoietic stem cell transplantation (HSCT) recipients in remission for both the CD38⁻ subset (P = .0127) and CD38⁺ subset (P = .0336).

Study details: The study included 7 MDS and 9 acute myeloid leukemia samples. Six HSCT recipients who remained in remission for more than 6 months were considered controls.

Disclosures: The study was supported by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf). The authors declared no conflicts of interest.

Source: Moskorz W et al. Br J Haematol. 2021 May 6. doi: 10.1111/bjh.17461.

Key clinical point: Inhibition of T cells by programmed death-ligand 1 (PD-L1)-expressing hematopoietic stem cells could be an underlying mechanism in the development of myelodysplastic syndrome (MDS). The findings support the potential use of immune checkpoint inhibitors in the treatment of suitable MDS patients.

Major finding: Significantly increased proportions of PD-L1⁺CD34⁺ stem cells were seen in MDS patients compared with hematopoietic stem cell transplantation (HSCT) recipients in remission for both the CD38⁻ subset (P = .0127) and CD38⁺ subset (P = .0336).

Study details: The study included 7 MDS and 9 acute myeloid leukemia samples. Six HSCT recipients who remained in remission for more than 6 months were considered controls.

Disclosures: The study was supported by the Düsseldorf School of Oncology (funded by the Comprehensive Cancer Center Düsseldorf/Deutsche Krebshilfe and the Medical Faculty HHU Düsseldorf). The authors declared no conflicts of interest.

Source: Moskorz W et al. Br J Haematol. 2021 May 6. doi: 10.1111/bjh.17461.

Key clinical point: Increased cumulative exposure to the alkylating agent melphalan increases the subsequent risk for developing acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Major finding: Cumulative exposure to melphalan was significantly higher (odds ratio, 2.8; P less than .001) among patients with MM and AML/MDS (median, 988 mg) than control participants (median, 578 mg). The median time to development of AML/MDS was 3.8 years.

Study details: The study included 26,627 patients diagnosed with MM between 1985 and 2011, of which 124 (0.5%) patients developed subsequent AML/MDS. Each patient with MM and AML/MDS diagnosis was matched with a control MM patient without AML/MDS.

Disclosures: The study was supported by grants from the Asrun Einarsdottir Foundation in Iceland, University of Iceland Research Fund, Icelandic Centre for Research, Landspitali University Hospital Research Fund, Thorman’s foundation, and Sylvester Comprehensive Cancer Center NCI Core Grant. O Landgren and M Björkholm reported ties with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Jonsdottir G et al. Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650.

Key clinical point: Increased cumulative exposure to the alkylating agent melphalan increases the subsequent risk for developing acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Major finding: Cumulative exposure to melphalan was significantly higher (odds ratio, 2.8; P less than .001) among patients with MM and AML/MDS (median, 988 mg) than control participants (median, 578 mg). The median time to development of AML/MDS was 3.8 years.

Study details: The study included 26,627 patients diagnosed with MM between 1985 and 2011, of which 124 (0.5%) patients developed subsequent AML/MDS. Each patient with MM and AML/MDS diagnosis was matched with a control MM patient without AML/MDS.

Disclosures: The study was supported by grants from the Asrun Einarsdottir Foundation in Iceland, University of Iceland Research Fund, Icelandic Centre for Research, Landspitali University Hospital Research Fund, Thorman’s foundation, and Sylvester Comprehensive Cancer Center NCI Core Grant. O Landgren and M Björkholm reported ties with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Jonsdottir G et al. Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650.

Key clinical point: Increased cumulative exposure to the alkylating agent melphalan increases the subsequent risk for developing acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM).

Major finding: Cumulative exposure to melphalan was significantly higher (odds ratio, 2.8; P less than .001) among patients with MM and AML/MDS (median, 988 mg) than control participants (median, 578 mg). The median time to development of AML/MDS was 3.8 years.

Study details: The study included 26,627 patients diagnosed with MM between 1985 and 2011, of which 124 (0.5%) patients developed subsequent AML/MDS. Each patient with MM and AML/MDS diagnosis was matched with a control MM patient without AML/MDS.

Disclosures: The study was supported by grants from the Asrun Einarsdottir Foundation in Iceland, University of Iceland Research Fund, Icelandic Centre for Research, Landspitali University Hospital Research Fund, Thorman’s foundation, and Sylvester Comprehensive Cancer Center NCI Core Grant. O Landgren and M Björkholm reported ties with various pharmaceutical companies. The remaining authors declared no conflicts of interest.

Source: Jonsdottir G et al. Eur J Haematol. 2021 May 9. doi: 10.1111/ejh.13650.

As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.¹ Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.

Cutaneous Vaccine Reactions and Facial Fillers

As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.² The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).^2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.⁴

Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.⁵ A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.⁶ The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.⁷

After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.^2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.⁹ The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.⁹

The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.³

Counseling Patients and Reducing Risks

As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.³

Managing Vaccine Reactions

If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.^3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,⁹ but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.

If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.² In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.

Final Thoughts

As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.

As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.¹ Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.

Cutaneous Vaccine Reactions and Facial Fillers

As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.² The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).^2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.⁴

Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.⁵ A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.⁶ The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.⁷

After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.^2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.⁹ The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.⁹

The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.³

Counseling Patients and Reducing Risks

As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.³

Managing Vaccine Reactions

If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.^3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,⁹ but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.

If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.² In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.

Final Thoughts

As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.

As we marked the 1-year anniversary of the COVID-19 pandemic, nearly 100 million Americans had received their first dose of the COVID-19 vaccine, heralding some sense of relief and enabling us to envision a return to something resembling life before lockdown.¹ Amid these breakthroughs and vaccination campaigns forging ahead worldwide, we saw new questions and problems arise. Vaccine hesitancy was already an issue in many segments of society where misinformation and mistrust of the medical establishment have served as barriers to the progress of public health. Once reports of adverse reactions following COVID-19 vaccination—such as those linked to use of facial fillers—made news headlines, many in the dermatology community began facing inquiries from patients questioning if they should wait to receive the vaccine or skip it entirely. As dermatologists, we must be informed and prepared to address these situations, to manage adverse reactions when they arise, and to encourage and promote vaccination during this critical time for public health in our society.

Cutaneous Vaccine Reactions and Facial Fillers

As public COVID-19 vaccinations move forward, dermatologic side effects, which were first noted during clinical trials, have received amplified attention, despite the fact that these cutaneous reactions—including localized injection-site redness and swelling, generalized urticarial and morbilliform eruptions, and even facial filler reactions—have been reported as relatively minor and self-limited.² The excipient polyethylene glycol has been suspected as a possible etiology of vaccine-related allergic and hypersensitivity reactions, suggesting care be taken in those who are patch-test positive or have a history of allergy to polyethylene glycol–containing products (eg, penicillin, laxatives, makeup, certain dermal fillers).^2,3 Although rare, facial and lip swelling reactions in those with a prior history of facial fillers in COVID-19 vaccine trials have drawn particular public concern and potential vaccine hesitancy given that more than 2.7 million Americans seek treatment with dermal fillers annually. There has been continued demand for these treatments during the pandemic, particularly due to aesthetic sensitivity surrounding video conferencing.⁴

Release of trial data from the Moderna COVID-19 vaccine prompted a discourse around safety and recommended protocols for filler procedures in the community of aesthetic medicine, as 3 participants in the experimental arm—all of whom had a history of treatment with facial filler injections—were reported to have facial or lip swelling shortly following vaccination. Two of these cases were considered to be serious adverse events due to extensive facial swelling, with the participants having received filler injections 6 months and 2 weeks prior to vaccination, respectively.⁵ A third participant experienced lip swelling only, which according to the US Food and Drug Administration briefing document was considered “medically significant” but not a serious adverse event, with unknown timing of the most recent filler injection. In all cases, symptom onset began 1 or 2 days following vaccination, and all resolved with either no or minimal intervention.⁶ The US Food and Drug Administration briefing document does not detail which type of fillers each participant had received, but subsequent reports indicated hyaluronic acid (HA) fillers. Of note, one patient in the placebo arm of the trial also developed progressive periorbital and facial edema in the setting of known filler injections performed 5 weeks prior, requiring treatment with corticosteroids and barring her from receiving a second injection in the trial.⁷

After public vaccination started, additional reports have emerged of facial edema occurring following administration of both the Pfizer and Moderna COVID-19 vaccines.^2,8,9 In one series, 4 cases of facial swelling were reported in patients who had HA filler placed more than 1 year prior to vaccination.⁹ The first patient, who had a history of HA fillers in the temples and cheeks, developed moderate periorbital swelling 2 days following her second dose of the Pfizer vaccine. Another patient who had received a series of filler injections over the last 3 years experienced facial swelling 24 hours after her second dose of the Moderna vaccine and also reported a similar reaction in the past following an upper respiratory tract infection. The third patient developed perioral and infraorbital edema 18 hours after her first dose of the Moderna vaccine. The fourth patient developed inflammation in filler-treated areas 10 days after the first dose of the Pfizer vaccine and notably had a history of filler reaction to an unknown trigger in 2019 that was treated with hyaluronidase, intralesional steroids, and 5-fluorouracil. All cases of facial edema reportedly resolved.⁹

The observed adverse events have been proposed as delayed-type hypersensitivity reactions (DTRs) to facial fillers and are suspected to be triggered by the COVID-19 spike protein and subsequent immunogenic response. This reaction is not unique to the COVID-19 vaccines; in fact, many inflammatory stimuli such as sinus infections, flulike illnesses, facial injury, dental procedures, and exposure to certain medications and chemotherapeutics have triggered DTRs in filler patients, especially in those with genetic or immunologic risk factors including certain human leukocyte antigen subtypes or autoimmune disorders.³

Counseling Patients and Reducing Risks

As reports of DTRs to facial fillers after COVID-19 vaccination continue to emerge, it is not surprising that patients may become confused by potential side effects and postpone vaccination as a result. This evolving situation has called upon aesthetic physicians to adapt our practice and prepare our patients. Most importantly, we must continue to follow the data and integrate evidence-based COVID-19 vaccine–related counseling into our office visits. It is paramount to encourage vaccination and inform patients that these rare adverse events are both temporary and treatable. Given the currently available data, patients with a history of treatment with dermal fillers should not be discouraged from receiving the vaccine; however, we may provide suggestions to lessen the likelihood of adverse reactions and ease patient concerns. For example, it may be helpful to consider a time frame between vaccination and filler procedures that is longer than 2 weeks, just as would be advised for those having dental procedures or with recent infections, and potentially longer windows for those with risk factors such as prior sensitivity to dermal fillers, autoimmune disorders, or those on immunomodulatory medications. Dilution of fillers with saline or lidocaine or use of non-HA fillers also may be suggested around the time of vaccination to mitigate the risk of DTRs.³

Managing Vaccine Reactions

If facial swelling does occur despite these precautions and lasts longer than 48 hours, treatment with antihistamines, steroids, and/or hyaluronidase has been successful in vaccine trial and posttrial patients, both alone or in combination, and are likely to resolve edema promptly without altering the effectiveness of the vaccine.^3,5,9 Angiotensin-converting enzyme inhibitors such as lisinopril more recently have been recommended for treatment of facial edema following COVID-19 vaccination,⁹ but questions remain regarding the true efficacy in this scenario given that the majority of swelling reactions resolve without this treatment. Additionally, there were no controls to indicate treatment with the angiotensin-converting enzyme inhibitor demonstrated an actual impact. Dermatologists generally are wary of adding medications of questionable utility that are associated with potential side effects and drug reactions, given that we often are tasked with managing the consequences of such mistakes. Thus, to avoid additional harm in the setting of insufficient evidence, as was seen following widespread use of hydroxychloroquine at the outset of the COVID-19 pandemic, well-structured studies are required before such interventions can be recommended.

If symptoms arise following the first vaccine injection, they can be managed if needed while patients are reassured and advised to obtain their second dose, with pretreatment considerations including antihistamines and instruction to present to the emergency department if a more severe reaction is suspected.² In a larger sense, we also can contribute to the collective knowledge, growth, and preparedness of the medical community by reporting cases of adverse events to vaccine reporting systems and registries, such as the US Department of Health and Human Services’ Vaccine Adverse Event Reporting System, the Centers for Disease Control and Prevention’s V-Safe After Vaccination Health Checker, and the American Academy of Dermatology’s COVID-19 Dermatology Registry.

Final Thoughts

As dermatologists, we now find ourselves in the familiar role of balancing the aesthetic goals of our patients with our primary mission of public health and safety at a time when their health and well-being is particularly vulnerable. Adverse reactions will continue to occur as larger segments of the world’s population become vaccinated. Meanwhile, we must continue to manage symptoms, dispel myths, emphasize that any dermatologic risk posed by the COVID-19 vaccines is far outweighed by the benefits of immunization, and promote health and education, looking ahead to life beyond the pandemic.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

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

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

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

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

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

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Pretransplant cytoreductive therapy is not associated with improved outcomes in patients with myelodysplastic syndromes (MDS) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Five-year overall survival after diagnosis was 73.6% (95% confidence interval [CI], 70.3%-76.9%), 43.4% (95% CI, 39.2%-47.6%), and 46.9% (95% CI, 44.7%-49.1%) in the upfront transplantation (upfront), induction chemotherapy (CT), and hypomethylating agents alone (HMA) groups, respectively (P = .033). Treatment-related mortality was 13.0% (95% CI, 11.4%-15.1%), 32.4% (95% CI, 30.1%-35.3%), and 28.4% (95% CI, 26.2%-30.3%) in the 3 groups, respectively (P = .028).

Study details: A total of 157 MDS patients were categorized into 3 groups based on the pretransplantation therapy: upfront (n=54), CT (n=66), and HMA (n=37). In addition, 124 patients underwent allo-HSCT.

Disclosures: This study was supported by the National Natural Science Foundation of China, Research and Development Program in Key Areas of Guangdong Province, Science and Technology Program of Guangzhou, and Clinical Research Start-up Project of Southern Medical University. The authors declared no conflicts of interest.

Source: Chen Y et al. Int J Cancer. 2021 Apr 25. doi: 10.1002/ijc.33608.

Key clinical point: Pretransplant cytoreductive therapy is not associated with improved outcomes in patients with myelodysplastic syndromes (MDS) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Five-year overall survival after diagnosis was 73.6% (95% confidence interval [CI], 70.3%-76.9%), 43.4% (95% CI, 39.2%-47.6%), and 46.9% (95% CI, 44.7%-49.1%) in the upfront transplantation (upfront), induction chemotherapy (CT), and hypomethylating agents alone (HMA) groups, respectively (P = .033). Treatment-related mortality was 13.0% (95% CI, 11.4%-15.1%), 32.4% (95% CI, 30.1%-35.3%), and 28.4% (95% CI, 26.2%-30.3%) in the 3 groups, respectively (P = .028).

Study details: A total of 157 MDS patients were categorized into 3 groups based on the pretransplantation therapy: upfront (n=54), CT (n=66), and HMA (n=37). In addition, 124 patients underwent allo-HSCT.

Disclosures: This study was supported by the National Natural Science Foundation of China, Research and Development Program in Key Areas of Guangdong Province, Science and Technology Program of Guangzhou, and Clinical Research Start-up Project of Southern Medical University. The authors declared no conflicts of interest.

Source: Chen Y et al. Int J Cancer. 2021 Apr 25. doi: 10.1002/ijc.33608.

Key clinical point: Pretransplant cytoreductive therapy is not associated with improved outcomes in patients with myelodysplastic syndromes (MDS) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Five-year overall survival after diagnosis was 73.6% (95% confidence interval [CI], 70.3%-76.9%), 43.4% (95% CI, 39.2%-47.6%), and 46.9% (95% CI, 44.7%-49.1%) in the upfront transplantation (upfront), induction chemotherapy (CT), and hypomethylating agents alone (HMA) groups, respectively (P = .033). Treatment-related mortality was 13.0% (95% CI, 11.4%-15.1%), 32.4% (95% CI, 30.1%-35.3%), and 28.4% (95% CI, 26.2%-30.3%) in the 3 groups, respectively (P = .028).

Study details: A total of 157 MDS patients were categorized into 3 groups based on the pretransplantation therapy: upfront (n=54), CT (n=66), and HMA (n=37). In addition, 124 patients underwent allo-HSCT.

Disclosures: This study was supported by the National Natural Science Foundation of China, Research and Development Program in Key Areas of Guangdong Province, Science and Technology Program of Guangzhou, and Clinical Research Start-up Project of Southern Medical University. The authors declared no conflicts of interest.

Source: Chen Y et al. Int J Cancer. 2021 Apr 25. doi: 10.1002/ijc.33608.

Case Report

A 67-year-old woman presented with a painful expanding ulcer on the left leg and a new nearby ulcer of 2 months’ duration. She initially was seen 2 months prior for a wound on the left knee due to a fall as well as cellulitis, which was treated with intravenous vancomycin and ceftriaxone. Wound cultures were negative for bacteria, and she was discharged without antibiotics. She presented to the emergency department 1 month later for malodorous discharge of the first ulcer with zero systemic inflammatory response syndrome criteria; no fever; and no abnormal heart rate, respiratory rate, or leukocyte count. She was discharged with wound care. After 3 weeks, she returned with a second ulcer and worsening drainage but zero systemic inflammatory response syndrome criteria. She had a medical history of Crohn disease with 9-year remission, atrial fibrillation, pacemaker, mitral valve replacement, chronic obstructive pulmonary disease, and a 51 pack-year smoking history.

Physical examination of the left leg revealed a 3×3-cm deep lesion (ulcer A) on the distal left thigh located superomedial to the knee (Figure 1) as well as a 2×1-cm deep lesion (ulcer B) on the anteromedial knee with undermining and tunneling (Figure 2). A large amount of malodorous tan bloody discharge was present on both ulcers. There were no signs of induration or crepitus.Due to concerns of skin and soft tissue infection (SSTI) or osteomyelitis, a bone scan and wound and blood cultures were ordered. The patient was started on vancomycin and piperacillin-tazobactam in the emergency department, which later was augmented with cefepime. Trauma surgery scheduled debridement for the following morning with suspicion of necrotizing fasciitis. Additional consultations were requested, including infectious disease, wound care, and dermatology. Dermatology evaluated the wound, performed a punch biopsy, and canceled debridement due to unclear diagnosis. The clinical differential at that time included pyoderma gangrenosum (PG), atypical vasculitis, or infection. Additional workup revealed positive antineutrophil cytoplasmic antibodies but negative proteinase 3 and myeloperoxidase, disfavoring vasculitis. Wound cultures grew Staphylococcus aureus and Pseudomonas aeruginosa.

Comment

Pyoderma gangrenosum is a rare inflammatory skin condition that classically presents as tender papules or pustules evolving into painful ulcers, most commonly on the lower extremities. Pyoderma gangrenosum has a propensity to exhibit pathergy, the hyperreactivity of the skin in response to minor trauma. This phenomenon in PG manifests as the rapid evolution from pustule to ulceration with violaceous undermining borders.

Diagnosis of PG
Pyoderma gangrenosum has been described as a diagnosis of exclusion, as its findings frequently mimic SSTIs. Important findings to obtain are histology, history, ulcer morphology, and response to treatment.

In 2018, Maverakis et al¹ proposed diagnostic criteria for classic ulcerative PG (Table 1). A diagnosis of PG can be made if the patient meets 1 major criterion and 4 minor criteria. Our case met 0 major criteria and 5 minor criteria: history of inflammatory bowel disease (IBD); history of pustule ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, with at least 1 on an anterior lower leg; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Although our patient’s biopsy demonstrated a mixed infiltrate, PG was not excluded due to spontaneous resolution at the time of biopsy, emphasizing the need to biopsy subsequent new lesions if neutrophils are not initially seen.¹ Pyoderma gangrenosum frequently is associated with IBD, most often Crohn disease, as seen in our patient.^2-4 Although IBD classically is associated with smoking, studies have yet to conclude if smoking is a predictive factor of PG.⁵ Our patient presented with an initial ulcer that evolved into 2 ulcers, similar to a case of bilateral ulcers.⁶

Management of PG
A gold standard of treatment of PG does not exist, but the goal is to promote wound healing. Patients with limited disease typically can be managed with wound care and topical steroids or calcineurin inhibitors, though data on efficacy are limited. However, our patient had more extensive disease and needed to be treated with systemic therapy. First-line therapy for extensive disease includes oral prednisone or cyclosporine for patients who cannot tolerate systemic corticosteroids.¹² Second-line and adjunctive therapy options include dapsone, minocycline, methotrexate, and infliximab. Our patient was prescribed a 7-month course of dapsone with outpatient dermatology and demonstrated resolution of both ulcers. Dapsone was tapered from a daily dose of 100 mg to 50 mg to 25 mg to none over the course of 2 to 3 months. Close monitoring with wound care is recommended, and petroleum jelly can be used for dry skin around the lesion for comfort.

Conclusion

The diagnosis of PG is challenging because it relies heavily on clinical signs and often mimics SSTI. Gathering a detailed medical history is critical to make the diagnosis of PG. In a patient with associated features of PG, dermatologic consultation and biopsy of skin lesions should be considered. Physicians should evaluate for suspected PG prior to proceeding with surgical intervention to avoid unnecessary amputation. The diagnostic criteria for classic ulcerative PG are gaining wider acceptance and are a useful tool for clinicians.

Case Report

A 67-year-old woman presented with a painful expanding ulcer on the left leg and a new nearby ulcer of 2 months’ duration. She initially was seen 2 months prior for a wound on the left knee due to a fall as well as cellulitis, which was treated with intravenous vancomycin and ceftriaxone. Wound cultures were negative for bacteria, and she was discharged without antibiotics. She presented to the emergency department 1 month later for malodorous discharge of the first ulcer with zero systemic inflammatory response syndrome criteria; no fever; and no abnormal heart rate, respiratory rate, or leukocyte count. She was discharged with wound care. After 3 weeks, she returned with a second ulcer and worsening drainage but zero systemic inflammatory response syndrome criteria. She had a medical history of Crohn disease with 9-year remission, atrial fibrillation, pacemaker, mitral valve replacement, chronic obstructive pulmonary disease, and a 51 pack-year smoking history.

Physical examination of the left leg revealed a 3×3-cm deep lesion (ulcer A) on the distal left thigh located superomedial to the knee (Figure 1) as well as a 2×1-cm deep lesion (ulcer B) on the anteromedial knee with undermining and tunneling (Figure 2). A large amount of malodorous tan bloody discharge was present on both ulcers. There were no signs of induration or crepitus.Due to concerns of skin and soft tissue infection (SSTI) or osteomyelitis, a bone scan and wound and blood cultures were ordered. The patient was started on vancomycin and piperacillin-tazobactam in the emergency department, which later was augmented with cefepime. Trauma surgery scheduled debridement for the following morning with suspicion of necrotizing fasciitis. Additional consultations were requested, including infectious disease, wound care, and dermatology. Dermatology evaluated the wound, performed a punch biopsy, and canceled debridement due to unclear diagnosis. The clinical differential at that time included pyoderma gangrenosum (PG), atypical vasculitis, or infection. Additional workup revealed positive antineutrophil cytoplasmic antibodies but negative proteinase 3 and myeloperoxidase, disfavoring vasculitis. Wound cultures grew Staphylococcus aureus and Pseudomonas aeruginosa.

Comment

Pyoderma gangrenosum is a rare inflammatory skin condition that classically presents as tender papules or pustules evolving into painful ulcers, most commonly on the lower extremities. Pyoderma gangrenosum has a propensity to exhibit pathergy, the hyperreactivity of the skin in response to minor trauma. This phenomenon in PG manifests as the rapid evolution from pustule to ulceration with violaceous undermining borders.

Diagnosis of PG
Pyoderma gangrenosum has been described as a diagnosis of exclusion, as its findings frequently mimic SSTIs. Important findings to obtain are histology, history, ulcer morphology, and response to treatment.

In 2018, Maverakis et al¹ proposed diagnostic criteria for classic ulcerative PG (Table 1). A diagnosis of PG can be made if the patient meets 1 major criterion and 4 minor criteria. Our case met 0 major criteria and 5 minor criteria: history of inflammatory bowel disease (IBD); history of pustule ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, with at least 1 on an anterior lower leg; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Although our patient’s biopsy demonstrated a mixed infiltrate, PG was not excluded due to spontaneous resolution at the time of biopsy, emphasizing the need to biopsy subsequent new lesions if neutrophils are not initially seen.¹ Pyoderma gangrenosum frequently is associated with IBD, most often Crohn disease, as seen in our patient.^2-4 Although IBD classically is associated with smoking, studies have yet to conclude if smoking is a predictive factor of PG.⁵ Our patient presented with an initial ulcer that evolved into 2 ulcers, similar to a case of bilateral ulcers.⁶

Management of PG
A gold standard of treatment of PG does not exist, but the goal is to promote wound healing. Patients with limited disease typically can be managed with wound care and topical steroids or calcineurin inhibitors, though data on efficacy are limited. However, our patient had more extensive disease and needed to be treated with systemic therapy. First-line therapy for extensive disease includes oral prednisone or cyclosporine for patients who cannot tolerate systemic corticosteroids.¹² Second-line and adjunctive therapy options include dapsone, minocycline, methotrexate, and infliximab. Our patient was prescribed a 7-month course of dapsone with outpatient dermatology and demonstrated resolution of both ulcers. Dapsone was tapered from a daily dose of 100 mg to 50 mg to 25 mg to none over the course of 2 to 3 months. Close monitoring with wound care is recommended, and petroleum jelly can be used for dry skin around the lesion for comfort.

Conclusion

The diagnosis of PG is challenging because it relies heavily on clinical signs and often mimics SSTI. Gathering a detailed medical history is critical to make the diagnosis of PG. In a patient with associated features of PG, dermatologic consultation and biopsy of skin lesions should be considered. Physicians should evaluate for suspected PG prior to proceeding with surgical intervention to avoid unnecessary amputation. The diagnostic criteria for classic ulcerative PG are gaining wider acceptance and are a useful tool for clinicians.

Case Report

A 67-year-old woman presented with a painful expanding ulcer on the left leg and a new nearby ulcer of 2 months’ duration. She initially was seen 2 months prior for a wound on the left knee due to a fall as well as cellulitis, which was treated with intravenous vancomycin and ceftriaxone. Wound cultures were negative for bacteria, and she was discharged without antibiotics. She presented to the emergency department 1 month later for malodorous discharge of the first ulcer with zero systemic inflammatory response syndrome criteria; no fever; and no abnormal heart rate, respiratory rate, or leukocyte count. She was discharged with wound care. After 3 weeks, she returned with a second ulcer and worsening drainage but zero systemic inflammatory response syndrome criteria. She had a medical history of Crohn disease with 9-year remission, atrial fibrillation, pacemaker, mitral valve replacement, chronic obstructive pulmonary disease, and a 51 pack-year smoking history.

Physical examination of the left leg revealed a 3×3-cm deep lesion (ulcer A) on the distal left thigh located superomedial to the knee (Figure 1) as well as a 2×1-cm deep lesion (ulcer B) on the anteromedial knee with undermining and tunneling (Figure 2). A large amount of malodorous tan bloody discharge was present on both ulcers. There were no signs of induration or crepitus.Due to concerns of skin and soft tissue infection (SSTI) or osteomyelitis, a bone scan and wound and blood cultures were ordered. The patient was started on vancomycin and piperacillin-tazobactam in the emergency department, which later was augmented with cefepime. Trauma surgery scheduled debridement for the following morning with suspicion of necrotizing fasciitis. Additional consultations were requested, including infectious disease, wound care, and dermatology. Dermatology evaluated the wound, performed a punch biopsy, and canceled debridement due to unclear diagnosis. The clinical differential at that time included pyoderma gangrenosum (PG), atypical vasculitis, or infection. Additional workup revealed positive antineutrophil cytoplasmic antibodies but negative proteinase 3 and myeloperoxidase, disfavoring vasculitis. Wound cultures grew Staphylococcus aureus and Pseudomonas aeruginosa.

Comment

Pyoderma gangrenosum is a rare inflammatory skin condition that classically presents as tender papules or pustules evolving into painful ulcers, most commonly on the lower extremities. Pyoderma gangrenosum has a propensity to exhibit pathergy, the hyperreactivity of the skin in response to minor trauma. This phenomenon in PG manifests as the rapid evolution from pustule to ulceration with violaceous undermining borders.

Diagnosis of PG
Pyoderma gangrenosum has been described as a diagnosis of exclusion, as its findings frequently mimic SSTIs. Important findings to obtain are histology, history, ulcer morphology, and response to treatment.

In 2018, Maverakis et al¹ proposed diagnostic criteria for classic ulcerative PG (Table 1). A diagnosis of PG can be made if the patient meets 1 major criterion and 4 minor criteria. Our case met 0 major criteria and 5 minor criteria: history of inflammatory bowel disease (IBD); history of pustule ulcerating within 4 days of appearing; peripheral erythema, undermining border, and tenderness at ulceration site; multiple ulcerations, with at least 1 on an anterior lower leg; and decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Although our patient’s biopsy demonstrated a mixed infiltrate, PG was not excluded due to spontaneous resolution at the time of biopsy, emphasizing the need to biopsy subsequent new lesions if neutrophils are not initially seen.¹ Pyoderma gangrenosum frequently is associated with IBD, most often Crohn disease, as seen in our patient.^2-4 Although IBD classically is associated with smoking, studies have yet to conclude if smoking is a predictive factor of PG.⁵ Our patient presented with an initial ulcer that evolved into 2 ulcers, similar to a case of bilateral ulcers.⁶

Management of PG
A gold standard of treatment of PG does not exist, but the goal is to promote wound healing. Patients with limited disease typically can be managed with wound care and topical steroids or calcineurin inhibitors, though data on efficacy are limited. However, our patient had more extensive disease and needed to be treated with systemic therapy. First-line therapy for extensive disease includes oral prednisone or cyclosporine for patients who cannot tolerate systemic corticosteroids.¹² Second-line and adjunctive therapy options include dapsone, minocycline, methotrexate, and infliximab. Our patient was prescribed a 7-month course of dapsone with outpatient dermatology and demonstrated resolution of both ulcers. Dapsone was tapered from a daily dose of 100 mg to 50 mg to 25 mg to none over the course of 2 to 3 months. Close monitoring with wound care is recommended, and petroleum jelly can be used for dry skin around the lesion for comfort.

Conclusion

The diagnosis of PG is challenging because it relies heavily on clinical signs and often mimics SSTI. Gathering a detailed medical history is critical to make the diagnosis of PG. In a patient with associated features of PG, dermatologic consultation and biopsy of skin lesions should be considered. Physicians should evaluate for suspected PG prior to proceeding with surgical intervention to avoid unnecessary amputation. The diagnostic criteria for classic ulcerative PG are gaining wider acceptance and are a useful tool for clinicians.