fifth issue
March 9, 2022
RDW/Hb ratio: the new best predictor of Mortality in Patients With Epidermal Necrolysis
JAMA Dermatology
You can only order one lab for prognosis–what is it going to be?! Epidermal necrolysis is a life-threatening blistering disorder that can lead to necrosis. Many providers have utilized Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for prognosis, but it has been shown to overestimate mortality so there was a need to revitalize this.. A retrospective cohort study was conducted from 2003 to 2019 from Singapore General Hospital, the national referral center for epidermal necrolysis (n = 192). They considered the ratios of red cell distribution width to hemoglobin, neutrophil to lymphocyte, platelet to lymphocyte, lymphocyte to monocyte, and mean platelet volume to platelets. Of these markers, only red cell distribution width to hemoglobin ratio was significant in predicting in-hospital mortality (odds ratio [OR] 3.55; 95% CI, 1.76-7.16; P < .001) after adjusting for SCORTEN. The optimal cutoff for RDW/Hb based on ROC curve analysis was 1.19 (OR, 9.68; 95% CI, 3.83-24.42; P < .001). When RDW/Hb was added to SCORTEN, the composite score Re-SCORTEN showed significantly better discrimination than SCORTEN alone (AUC [95% CI]: Re-SCORTEN, 0.83 [0.77-0.89], vs SCORTEN, 0.78 [0.70-0.85], P = .02). RDW/Hb ratio is inexpensive to order and should be calculated when evaluating a patient with epidermal necrolysis. Furthermore, SCORTEN can be updated to include this value and further improve prognostic accuracy.
Which medications are highest risk for skin cancer in organ transplant patients?
Journal of American Academy of Dermatology
When you solve one problem, another appears. Transplant patients are at higher risk for developing skin cancers, especially cutaneous squamous cell carcinoma (cSCC). You may be thinking…why? This is due largely to the use of immunosuppressants used in transplant patients. Over the years, we’ve learned that not all medications are created equal with respect to their risk for skin cancers and so transplant medications should be chosen carefully! This cohort and nested case-control study sought to identify the risk of cSCC based on medications by reviewing pathology data and medications for 3,308 solid organ transplant recipients and 65,883 persons without transplantation during 2000-2019. They found that the the biggest culprit medications were 1) voriconazole (hazard ratio of 1.14 for each month of voriconazole use [95% CI, 1.04-1.26]), which was used to treat lung recipients with fungal infections, and 2) azathioprine, when used in those intolerant to mycophenolate mofetil (cellcept) (4.22-fold increased risk of cSCC [95% CI, 1.90-9.40]). Lung transplant patients had the highest risk of developing cSCC with a hazard ratio of 14.83 (95% CI, 9.85-22.33). Other risk factors include White and Latinx race/ethnicity, older age, and history of skin cancer. Limitations include the small number of patients who had cSCC (n=246) and that they could not carefully analyze drug switches. Regardless, it is important to counsel transplant patients about the increased risk of cSCC when using medications such as azathioprine and voriconazole and make sure they see their dermatologists for regular skin checks!
β-defensins: the role of peptides in chronic pruritus
Journal of Investigative Dermatology
Ever wondered why patients can have long-standing pruritic symptoms despite taking antihistamines? Shouldn’t they block mast cell degranulation and prevent itch? Scientists have wondered this too and are interested in the role the β-defensin family of peptides play in itch. Studying publicly available RNA-sequencing data of skin biopsies of patients with psoriasis and atopic dermatitis, researchers identified that the DEFB103 and DEFB4 genes, which encode β-defensins, were upregulated in psoriasis and AD patients. Using immortalized human mast cells, they examined the effect of gene activation on mast cell degranulation and found the DEFB103 gene was ten times more potent in causing mast cell degranulation. Results were confirmed using mouse models. An unexpected finding of the mouse model experiments was that β-defensins also stimulate sensory neurons, potentially to a greater degree than they do mast cells. The findings of this study are significant because they elucidate how peptides are involved in itch response, and additionally highlight neuronal involvement in pruritus. While considerable further research must be done, this is exciting news for patients suffering from conditions with chronic pruritus that new therapies may one day become available!
JAMA Dermatology
You can only order one lab for prognosis–what is it going to be?! Epidermal necrolysis is a life-threatening blistering disorder that can lead to necrosis. Many providers have utilized Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for prognosis, but it has been shown to overestimate mortality so there was a need to revitalize this.. A retrospective cohort study was conducted from 2003 to 2019 from Singapore General Hospital, the national referral center for epidermal necrolysis (n = 192). They considered the ratios of red cell distribution width to hemoglobin, neutrophil to lymphocyte, platelet to lymphocyte, lymphocyte to monocyte, and mean platelet volume to platelets. Of these markers, only red cell distribution width to hemoglobin ratio was significant in predicting in-hospital mortality (odds ratio [OR] 3.55; 95% CI, 1.76-7.16; P < .001) after adjusting for SCORTEN. The optimal cutoff for RDW/Hb based on ROC curve analysis was 1.19 (OR, 9.68; 95% CI, 3.83-24.42; P < .001). When RDW/Hb was added to SCORTEN, the composite score Re-SCORTEN showed significantly better discrimination than SCORTEN alone (AUC [95% CI]: Re-SCORTEN, 0.83 [0.77-0.89], vs SCORTEN, 0.78 [0.70-0.85], P = .02). RDW/Hb ratio is inexpensive to order and should be calculated when evaluating a patient with epidermal necrolysis. Furthermore, SCORTEN can be updated to include this value and further improve prognostic accuracy.
Which medications are highest risk for skin cancer in organ transplant patients?
Journal of American Academy of Dermatology
When you solve one problem, another appears. Transplant patients are at higher risk for developing skin cancers, especially cutaneous squamous cell carcinoma (cSCC). You may be thinking…why? This is due largely to the use of immunosuppressants used in transplant patients. Over the years, we’ve learned that not all medications are created equal with respect to their risk for skin cancers and so transplant medications should be chosen carefully! This cohort and nested case-control study sought to identify the risk of cSCC based on medications by reviewing pathology data and medications for 3,308 solid organ transplant recipients and 65,883 persons without transplantation during 2000-2019. They found that the the biggest culprit medications were 1) voriconazole (hazard ratio of 1.14 for each month of voriconazole use [95% CI, 1.04-1.26]), which was used to treat lung recipients with fungal infections, and 2) azathioprine, when used in those intolerant to mycophenolate mofetil (cellcept) (4.22-fold increased risk of cSCC [95% CI, 1.90-9.40]). Lung transplant patients had the highest risk of developing cSCC with a hazard ratio of 14.83 (95% CI, 9.85-22.33). Other risk factors include White and Latinx race/ethnicity, older age, and history of skin cancer. Limitations include the small number of patients who had cSCC (n=246) and that they could not carefully analyze drug switches. Regardless, it is important to counsel transplant patients about the increased risk of cSCC when using medications such as azathioprine and voriconazole and make sure they see their dermatologists for regular skin checks!
β-defensins: the role of peptides in chronic pruritus
Journal of Investigative Dermatology
Ever wondered why patients can have long-standing pruritic symptoms despite taking antihistamines? Shouldn’t they block mast cell degranulation and prevent itch? Scientists have wondered this too and are interested in the role the β-defensin family of peptides play in itch. Studying publicly available RNA-sequencing data of skin biopsies of patients with psoriasis and atopic dermatitis, researchers identified that the DEFB103 and DEFB4 genes, which encode β-defensins, were upregulated in psoriasis and AD patients. Using immortalized human mast cells, they examined the effect of gene activation on mast cell degranulation and found the DEFB103 gene was ten times more potent in causing mast cell degranulation. Results were confirmed using mouse models. An unexpected finding of the mouse model experiments was that β-defensins also stimulate sensory neurons, potentially to a greater degree than they do mast cells. The findings of this study are significant because they elucidate how peptides are involved in itch response, and additionally highlight neuronal involvement in pruritus. While considerable further research must be done, this is exciting news for patients suffering from conditions with chronic pruritus that new therapies may one day become available!
QUESTION OF THE WEEK
NEJM CHALLENGE QUESTION
A 49-year-old woman, who had undergone kidney transplantation 4 months earlier, presented to the emergency department with a 2-week history of headache, dizziness, and rash. On exam she had diffuse, umbilicated papules. What is the most likely pathogen?
- Blastomyces dermatitidis
- Cryptococcus neoformans
- Histoplasma capsulatum
- Molluscum contagiosum
- Mycobacterium tuberculosis
Answer:
Cryptococcus neoformans
Serum and cerebrospinal fluid (CSF) cryptococcal antigen titers were significantly elevated. Cryptococcus neoformans was grown on culture of the CSF. India ink stain of CSF showed encapsulated budding yeast. A biopsy specimen of the skin obtained from the patient’s left arm showed numerous yeastlike organisms surrounded by mucinous capsules, confirming a diagnosis of disseminated cryptococcosis. She was treated with liposomal amphotericin B and flucytosine. In immunocompromised patients, umbilicated skin lesions may be caused by cryptococcus. Treatment with liposomal amphotericin B and flucytosine was initiated, and the cutaneous and central nervous system symptoms resolved.
Other answers:
Blastomyces dermatitidis- This causes blastomycosis which is characterized by verrucous nodules, abscesses and ulcers. Pulmonary manifestations are very common. Microscopy shows broad-based buds (this is definitely a buzz word!). Geographic location includes Eastern united states, Great Lakes, Ohio, and Mississippi River valleys
Histoplasma capsulatum- This causes histoplasmosis, which is characterized clinically by secondary cutaneous molluscoid nodules (so this can also present with umbilicated papules), cellulitis, panniculitis and oral lesions. Pulmonary complications are the most common presentation. Geographic location includes Ohio and Mississippi River valley. Pathology would show tuberculoid granuloma with intracellular 2-4 micrometer yeast in histiocytes.
Molluscum contagiosum- dome-shaped papules that can be seen in immunocompetent individuals, especially children, and also can be disseminated in immunocompromised such as HIV patients. Interestingly, in HIV, patients typically lack classic dome shaped appearance and central umbilication. Pathology shows molluscum bodies in dermis
Mycobacterium tuberculosis- can have various dermatologic presentations and pathology shows granulomas with central caseation and the presence of acid-fast bacilli
Cryptococcus neoformans
Serum and cerebrospinal fluid (CSF) cryptococcal antigen titers were significantly elevated. Cryptococcus neoformans was grown on culture of the CSF. India ink stain of CSF showed encapsulated budding yeast. A biopsy specimen of the skin obtained from the patient’s left arm showed numerous yeastlike organisms surrounded by mucinous capsules, confirming a diagnosis of disseminated cryptococcosis. She was treated with liposomal amphotericin B and flucytosine. In immunocompromised patients, umbilicated skin lesions may be caused by cryptococcus. Treatment with liposomal amphotericin B and flucytosine was initiated, and the cutaneous and central nervous system symptoms resolved.
Other answers:
Blastomyces dermatitidis- This causes blastomycosis which is characterized by verrucous nodules, abscesses and ulcers. Pulmonary manifestations are very common. Microscopy shows broad-based buds (this is definitely a buzz word!). Geographic location includes Eastern united states, Great Lakes, Ohio, and Mississippi River valleys
Histoplasma capsulatum- This causes histoplasmosis, which is characterized clinically by secondary cutaneous molluscoid nodules (so this can also present with umbilicated papules), cellulitis, panniculitis and oral lesions. Pulmonary complications are the most common presentation. Geographic location includes Ohio and Mississippi River valley. Pathology would show tuberculoid granuloma with intracellular 2-4 micrometer yeast in histiocytes.
Molluscum contagiosum- dome-shaped papules that can be seen in immunocompetent individuals, especially children, and also can be disseminated in immunocompromised such as HIV patients. Interestingly, in HIV, patients typically lack classic dome shaped appearance and central umbilication. Pathology shows molluscum bodies in dermis
Mycobacterium tuberculosis- can have various dermatologic presentations and pathology shows granulomas with central caseation and the presence of acid-fast bacilli
