Fifty-fifth issue
March 6, 2024
Patient-reported outcomes and mortality in cutaneous chronic graft-vs-host disease
JAMA Dermatology
JAMA Dermatology
GVHD: putting the “host” in “hostility”
Chronic graft-versus-host disease (GVHD) complicates 30% to 50% of allogeneic hematopoietic cell transplants, is the primary cause of morbidity and non relapse mortality post-transplant, and has skin involvement in up to 80% of cases. This study aimed to examine the difference between sclerosis and epidermal-type chronic GVHD with longitudinal patient-reported outcomes (PROs) to assess if PROs can effectively identify individuals with a higher mortality risk.
This multicenter prospective cohort study, consisting of 436 patients with chronic GVHD with skin involvement requiring systemic immunosuppression, measured patient-reported symptom burden using the Lee Symptom Scale (LSS) skin subscale and quality of life using the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) instrument.
What did they find?
Limitations: It is hard to establish how the results may apply to patients with skin-limited chronic GVHD as most patients had extracutaneous involvement. The results may not apply to patients who are not treated with systemic immunosuppression.
Main Takeaway: Sclerotic and combination GVHD had the highest morbidity. Worse PROs of cutaneous GVHD at diagnosis are a potential prognostic marker of mortality, highlighting the possible utility of PROs for risk stratification.
Chronic graft-versus-host disease (GVHD) complicates 30% to 50% of allogeneic hematopoietic cell transplants, is the primary cause of morbidity and non relapse mortality post-transplant, and has skin involvement in up to 80% of cases. This study aimed to examine the difference between sclerosis and epidermal-type chronic GVHD with longitudinal patient-reported outcomes (PROs) to assess if PROs can effectively identify individuals with a higher mortality risk.
This multicenter prospective cohort study, consisting of 436 patients with chronic GVHD with skin involvement requiring systemic immunosuppression, measured patient-reported symptom burden using the Lee Symptom Scale (LSS) skin subscale and quality of life using the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) instrument.
What did they find?
- 131 patients with sclerotic chronic GVHD (52.5%), 229 patients with epidermal-type chronic GVHD (30.0%), and 76 patients with a combination (17.4%) were identified
- Patients with combination disease had an average LSS skin subscale score 9.0 points worse than patients with epidermal-type GVHD (95% CI, 4.2-13.8, P < 0.001)
- Patients with sclerotic chronic GVHD had an average FACT-BMT score 6.1 points less than patients with epidermal-type GVHD (95% CI, 11.7-0.4; P = 0.04)
- Clinical meaningful worsening in LSS skin subscale score (defined as 11 points higher) was associated with a 16.4% higher risk of non relapse mortality (95% CI, 5.4%-28.5%, P = 0.003)
- Clinical meaningful worsening in FACT-BMT score (defined as 7 points lower) at diagnosis was associated with a 9.1% higher risk of non relapse mortality (95% CI, 2.0%-16.7%, P = 0.01)
Limitations: It is hard to establish how the results may apply to patients with skin-limited chronic GVHD as most patients had extracutaneous involvement. The results may not apply to patients who are not treated with systemic immunosuppression.
Main Takeaway: Sclerotic and combination GVHD had the highest morbidity. Worse PROs of cutaneous GVHD at diagnosis are a potential prognostic marker of mortality, highlighting the possible utility of PROs for risk stratification.
Comparison of incidence and timing of subsequent squamous cell carcinomas in patients with organ transplant and hematologic malignancies vs. general population
Journal of American Academy Dermatology
Journal of American Academy Dermatology
Transplants: Giving you a second chance at life, but a first-row seat to the sun’s revenge. Stay shady, stay safe!
With an annual incidence of 2.4 million cases, cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the world. It has been reported that patients with a compromised immune system, such as solid organ transplant recipients (SOTRs) and patients with hematologic malignancy (HM), have a 65- to 250-times higher risk of developing cSCC. While the literature has addressed the initial risk of developing cSCC, minimal research has explored the risk of developing subsequent cSSCs. This study utilized a nationwide cohort of 12,345 patients with cSCC (250 SOTRs and 674 HM) from the Netherlands Cancer Registry to address this gap in the literature.
What did they find?
Of the 12,345 patients included in the cohort, approximately one third (35%, n=4325) developed at least one additional cSCC
Main takeaway: There is increased risk of subsequent cSCC development in immunocompromised patients, especially those who have undergone solid organ transplant. Time to development of subsequent cSCC is decreased in those who have already developed cSCC.
With an annual incidence of 2.4 million cases, cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the world. It has been reported that patients with a compromised immune system, such as solid organ transplant recipients (SOTRs) and patients with hematologic malignancy (HM), have a 65- to 250-times higher risk of developing cSCC. While the literature has addressed the initial risk of developing cSCC, minimal research has explored the risk of developing subsequent cSSCs. This study utilized a nationwide cohort of 12,345 patients with cSCC (250 SOTRs and 674 HM) from the Netherlands Cancer Registry to address this gap in the literature.
What did they find?
Of the 12,345 patients included in the cohort, approximately one third (35%, n=4325) developed at least one additional cSCC
- 2,010 developed a third
- 1,138 developed a fourth
- 739 developed a fifth
- 501 developed a sixth cSCC
- Once a SOTR has developed a first cSCC, the average time to occurrence of a second cSCC is 8 months
- Broadly, males had a higher risk for a second and third cSCC (31% and 44% respectively) than females (23% and 38% respectively)
- The risk of subsequent cSCC development over the 5 years following initial diagnosis was 74% for SOTRs, 42% for HM, and 28% for non-SOTR/HM cohort members
Main takeaway: There is increased risk of subsequent cSCC development in immunocompromised patients, especially those who have undergone solid organ transplant. Time to development of subsequent cSCC is decreased in those who have already developed cSCC.
Does anatomic region matter regarding the duration of action of local lidocaine anesthesia?
Dermatologic Surgery
Dermatologic Surgery
Stop the pain with more Lidocaine!
The nose is a common anatomic site in dermatologic surgery - adequate pain control to this area is paramount. Previous studies have suggested that highly vascularized areas have both greater absorption and peak plasma concentrations of local anesthetic compared to lesser-vascularized areas. Few have examined how the duration of action of local anesthetics differs based on anatomic region.
This prospective clinical study assessed the duration of lidocaine anesthesia in the nasal ala and the shin, comparing highly and poorly vascularized anatomic regions respectively. Patients’ (N = 25) sensitivity to sharpness using pinprick testing was assessed at baseline and at 15 minute increments after lidocaine injection until return of sensation occurred.
What did they find?
The nose is a common anatomic site in dermatologic surgery - adequate pain control to this area is paramount. Previous studies have suggested that highly vascularized areas have both greater absorption and peak plasma concentrations of local anesthetic compared to lesser-vascularized areas. Few have examined how the duration of action of local anesthetics differs based on anatomic region.
This prospective clinical study assessed the duration of lidocaine anesthesia in the nasal ala and the shin, comparing highly and poorly vascularized anatomic regions respectively. Patients’ (N = 25) sensitivity to sharpness using pinprick testing was assessed at baseline and at 15 minute increments after lidocaine injection until return of sensation occurred.
What did they find?
- Participants regained sensation to the nose significantly faster (72.6 minutes) than to the shin (120.9 minutes) (p < .0001)
- At 1 hour: 60% of participants regained sensation to their nose and 8% regained sensation to their shin (p < .0008)
- On average, men regained sensation on their nose in 58 minutes while females on average regained sensation on their nose in 96 minutes (p = .01)
Homozygous Loss of CDKN2 in Primary Cutaneous CD8(+) Lymphoma NOS
American Journal of Dermatopathology
American Journal of Dermatopathology
Dispel PCAL
Primary cutaneous acral CD8+ lymphoma (PCAL) commonly presents on the ears as erythematous papules or nodules that follow a benign, indolent course. P16 protein is encoded by 9p21 and binds to cyclin dependent kinases 2 and 4 to inhibit cell cycle progression at the G1/S checkpoint. A single aggressive case of PCAL showed a deletion of the CDKN2 locus at 9p21, leading researchers to assess this gene in other cases of PCAL.
Researchers analyzed the expression of p16 protein and the integrity of CDKN2A locus in 4 cases of classical PCAL and 1 aggressive case of PCAL. P16 expression was assessed using immunohistochemistry and the integrity of the CDKN2A locus on 9p21 was analyzed using FISH.
What did they find?
Main Takeaways: Analysis of p16 protein expression and the CDKN2A locus on 9p21 may be useful predictors of the clinical severity of PCAL.
Primary cutaneous acral CD8+ lymphoma (PCAL) commonly presents on the ears as erythematous papules or nodules that follow a benign, indolent course. P16 protein is encoded by 9p21 and binds to cyclin dependent kinases 2 and 4 to inhibit cell cycle progression at the G1/S checkpoint. A single aggressive case of PCAL showed a deletion of the CDKN2 locus at 9p21, leading researchers to assess this gene in other cases of PCAL.
Researchers analyzed the expression of p16 protein and the integrity of CDKN2A locus in 4 cases of classical PCAL and 1 aggressive case of PCAL. P16 expression was assessed using immunohistochemistry and the integrity of the CDKN2A locus on 9p21 was analyzed using FISH.
What did they find?
- 3 cases showed p16 protein expression by a minority of neoplastic T-cells, varying from 5% to 20% on immunohistochemistry
- 2 cases including the atypical tumor were almost completely negative for p16 protein, with <1% expression and 0 expression on immunohistochemistry
- The 4 classical cases of PCAL showed a normal pattern for the CDKN2A locus at 9p21 on FISH analysis
- The atypical tumor showed an abnormal signal for the CDKN2A locus at 9p21, indicating loss of this locus
Main Takeaways: Analysis of p16 protein expression and the CDKN2A locus on 9p21 may be useful predictors of the clinical severity of PCAL.
Does vitamin D supplementation enhance the therapeutic effect of excimer laser on vitiligo?
Journal of Cosmetic Dermatology
Journal of Cosmetic Dermatology
Vitamin D and phototherapy: A ray of hope for vitiligo treatment!
Vitiligo is a skin condition characterized by autoimmune-mediated loss of melanocytes, resulting in non-pigmented patches on the skin. Treatment options include topical and systemic corticosteroids, phototherapy, and skin grafting though results vary from person to person. It’s suggested that vitamin D may influence the pathogenesis of vitiligo. Therefore, researchers investigated whether supplementation with vitamin D enhanced the therapeutic effects of excimer laser in vitiligo patients.
This prospective, randomized controlled study included patients with vitiligo with low serum 25(OH)D levels (n=26). Both groups received 308-nm excimer laser twice weekly and tacrolimus 0.1% ointment twice daily. The study group received additional one-time intramuscular vitamin D supplementation. Clinical assessments using the vitiligo area scoring index (VASI) were conducted monthly for 6 months.
What did they find:
Main takeaway: Vitamin D supplementation, when combined with phototherapy, shows promising synergistic effects in improving the therapeutic outcomes for vitiligo patients with vitamin D deficiency.
Vitiligo is a skin condition characterized by autoimmune-mediated loss of melanocytes, resulting in non-pigmented patches on the skin. Treatment options include topical and systemic corticosteroids, phototherapy, and skin grafting though results vary from person to person. It’s suggested that vitamin D may influence the pathogenesis of vitiligo. Therefore, researchers investigated whether supplementation with vitamin D enhanced the therapeutic effects of excimer laser in vitiligo patients.
This prospective, randomized controlled study included patients with vitiligo with low serum 25(OH)D levels (n=26). Both groups received 308-nm excimer laser twice weekly and tacrolimus 0.1% ointment twice daily. The study group received additional one-time intramuscular vitamin D supplementation. Clinical assessments using the vitiligo area scoring index (VASI) were conducted monthly for 6 months.
What did they find:
- Significant reduction in VASI score for the treatment group after 1 month (p=0.001)
- At 3 months of treatment, the study group had 70.1% improvement in VASI score compared to 39.2% in the control group (p=0.013)
- 75% of participants in the study group demonstrated over a 50% improvement in repigmentation after 6 months, whereas only 42.8% of the control group showed improvement in repigmentation though not statistically significant (p=0.098)
- After 6 months of treatment, the treatment group showed an 83.6% improvement in the initial VASI score, whereas the control group showed a 54.7% improvement
Main takeaway: Vitamin D supplementation, when combined with phototherapy, shows promising synergistic effects in improving the therapeutic outcomes for vitiligo patients with vitamin D deficiency.
Permanent cosmetic procedures, notably tattooing, have been identified as risk factors associated with the development of cutaneous granulomatous conditions, such as scar sarcoidosis.
Our case report features a 48-year-old Hispanic female who developed scar sarcoidosis progressing to a systemic sarcoidosis, underscoring the importance of early detection in cutaneous sarcoidosis within long standing scars due to potential systemic risks. The patient underwent three permanent makeup tattooing procedures on her eyebrows years before disease onset. Simultaneously, she experienced symptoms of pulmonary sarcoidosis for six months, including dry cough, shortness of breath, and intermittent wheezing.
While cutaneous sarcoidosis isolated to scars is uncommon, its cutaneous presentation is analogous to keloids, leading to potential misdiagnosis. Thus, when evaluating patients with enlarging or exacerbated pre-existing scars, sarcoidosis should be considered in the differential diagnoses. This case illustrates a rare presentation of cutaneous sarcoidosis induced by permanent makeup procedures on the eyebrows.
Our case report features a 48-year-old Hispanic female who developed scar sarcoidosis progressing to a systemic sarcoidosis, underscoring the importance of early detection in cutaneous sarcoidosis within long standing scars due to potential systemic risks. The patient underwent three permanent makeup tattooing procedures on her eyebrows years before disease onset. Simultaneously, she experienced symptoms of pulmonary sarcoidosis for six months, including dry cough, shortness of breath, and intermittent wheezing.
- Histopathological examination of a lesion excised from the left central eyebrow revealed non-caseating epithelioid cell granulomas, confirming the sarcoidosis diagnosis
- Inclusion bodies were observed in the clusters of granulomas, such as asteroid bodies and Schaumann bodies
- pulmonary function testing revealed small airway disease
While cutaneous sarcoidosis isolated to scars is uncommon, its cutaneous presentation is analogous to keloids, leading to potential misdiagnosis. Thus, when evaluating patients with enlarging or exacerbated pre-existing scars, sarcoidosis should be considered in the differential diagnoses. This case illustrates a rare presentation of cutaneous sarcoidosis induced by permanent makeup procedures on the eyebrows.