Krista Reznik – Derm In-Review

May 2024 Case Study

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May 2024 Case Study

Authors: Sara Abdel Azim, MS1,2, Kamaria Nelson, MD1, Karl Saardi, MD1

  1. Department of Dermatology, George Washington University School of Medicine and Health Sciences
  2. Georgetown University School of Medicine

A 63-year-old female with a past medical history of substance use disorder and breast cancer status post bilateral mastectomy presented with large, violaceous, hemorrhagic purpuric plaques on the chest and bilateral axilla (Fig 1). She had a fever of 104 F and heart rate of 140 bpm. She was admitted to the hospital for atrial fibrillation with rapid ventricular response and was found to be thrombocytopenic with a positive blood culture for streptococcus pyogenes. Coagulation studies revealed a prolonged PTT, an elevated INR level and a low fibrinogen level.

Which of the following is the diagnosis?

A.) Anti-phospholipid syndrome
B.) Calciphylaxis
C.) ANCA associated vasculitis
D.) Purpura fulminans
E.) Warfarin-induced skin necrosis

 

Correct Answer: D – Purpura fulminans

Explanation/Literature review:

Based on the patient’s manifestation of large, hemorrhagic purpuric plaques, acute systemic infection, and concurrent findings of disseminated intravascular coagulation on laboratory tests, she was diagnosed with purpura fulminans (choice D).

Purpura fulminans is a dermatologic emergency involving dysfunction of hemostasis, leading to a hypercoagulable state and ultimately disseminated intravascular coagulation and dermal vascular thrombosis.1  Patients present with ecchymotic skin lesions that may progress to gangrene and result in amputation. Acute infectious purpura fulminans is the most common subtype and occurs in the setting of sepsis, with endotoxin producing gram-negative bacteria triggering an acquired consumption of protein C and S and antithrombin III. 2,3 The most common pathogens are meningococcus and streptococcus pneumoniae, though streptococcus pyogenes has also been implicated.4

Antiphospholipid syndrome (APS) (choice A) is an autoimmune disease characterized by the presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibody, and anti-B2-glycoprotein antibody, that damage endothelial cells and disrupt procoagulation defenses, promoting thrombosis.5 Livedo reticularis the most frequently observed lesion, though APS can also cause ulcerations, digital gangrene, subungual splinter hemorrhages, superficial venous thrombosis, and thrombocytopenic purpura. APS occurs secondary to autoimmune disease, most commonly systemic lupus erythematosus (40% of secondary cases)6 or can be primary. Though infections such as borrelia burgdorferi, treponema, HIV, and leptospira have been implicated in the induction of antiphospholipid antibody formation, septicemia is not a common cause of APS and associated disseminated intravascular coagulation is a less common outcome(choice A).7

Calciphylaxis  (choice B) is caused by cutaneous arteriolar calcification that leads to subsequent tissue ischemia.8 It presents as violaceous or erythematous, painful cutaneous lesions or subcutaneous nodules and nonhealing wounds, commonly involving adipose-dense regions such as the abdomen, thighs, and buttocks. Calciphylaxis most commonly presents in patients with end stage renal disease but can also occur in patients with acute renal failure, normal renal function, or early stages of chronic kidney disease.

Antineutrophilic cytoplasmic antibody (ANCA) (choice C) associated vasculitis are a heterogenous group of autoimmune conditions that cause inflammation of blood vessels.9 The most common cutaneous manifestation is palpable purpura, though presentation may consist of polymorphic lesions on a background of livedo reticularis.10 This group of conditions has multisystemic effects, often involving the kidneys, sinopulmonary tract, gastrointestinal tract, and lungs, depending on subtype. Infection should be excluded before making the diagnosis.

Warfarin-induced skin necrosis (choice E) occurs in individuals under warfarin treatment with a thrombophilic history or after initiating warfarin therapy with a large loading dose or without concomitant heparin

References

  1. Bektas F, Soyuncu S. Idiopathic purpura fulminans. Am J Emerg Med. May 2011;29(4):475.e5-6. doi:10.1016/j.ajem.2010.04.022
  2. Perera T, Murphy-Lavoie H. Purpura Fulminans. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
  3. Kim MC, Patel J. Recognition and Management of Acute Purpura Fulminans: A Case Report of a Complication of Neisseria meningitidis Bacteremia. Cureus. Mar 04 2021;13(3):e13704. doi:10.7759/cureus.13704
  4. Okuzono S, Ishimura M, Kanno S, et al. Streptococcus pyogenes-purpura fulminans as an invasive form of group A streptococcal infection. Ann Clin Microbiol Antimicrob. Jul 09 2018;17(1):31. doi:10.1186/s12941-018-0282-9
  5. Magdaleno-Tapial J, Valenzuela-Oñate C, Pitarch-Fabregat J, et al. Purpura fulminans-like lesions in antiphospholipid syndrome with endothelial C3 deposition. JAAD Case Rep. Oct 2018;4(9):956-958. doi:10.1016/j.jdcr.2018.09.006
  6. Bustamant J, Goyal A, Singhal M. Antiphospholipid Syndrome. Treasure Island (FL): StatPearls Publishing. Accessed May 2, 2024. https://www.ncbi.nlm.nih.gov/books/NBK430980/
  7. Asherson RA, Espinosa G, Cervera R, et al. Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients. Ann Rheum Dis. Jun 2005;64(6):943-6. doi:10.1136/ard.2004.026377
  8. Westphal S, Plumb T. Calciphylaxis. Treasure Island (FL): StatPearls Publishing. Accessed May 2, 2024. https://www.ncbi.nlm.nih.gov/books/NBK519020/
  9. Qasim A, Patel J. ANCA Positive Vasculitis. Treasure Island (FL): StatPearls Publishing. Accessed May 2, 2024. https://www.ncbi.nlm.nih.gov/books/NBK554372/

April 2024 Case Study

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April 2024 Case Study

Author: Adam Rosenfeld, MD1

  1. Department of Dermatology, George Washington University School of Medicine and Health Sciences

A 79-year-old gentleman presented to the ED with altered mental status. The day prior, his family had found him “confused and weak” which resolved by later that evening. However, the next day, he was “dazed” had difficulty walking, which sparked the presentation to the emergency room. On examination, the patient was found to have an erythematous to violaceous, somewhat reticulated plaque on the posterior neck with a background of mottled, reddish-brown patches (figure 1). On the left hand, he was found to have eroded erythematous papules of the MCPs, PIPs, DIPs and in between the joint spaces (figure 2).

Based on the most likely diagnosis, which of the following would not be a reasonable part of the work up in adult patients?

A.) Pulmonary function tests
B.) CA 19-9
C.) CT chest/abdomen/pelvis
D.) MRI brain
E.) EKG/echocardiogram

  

 

Correct Answer: D – MRI Brain

Explanation/Literature review:

Poikiloderma of the neck, with classic “Gottron’s papules” on the left hand, are most concerning for a diagnosis of dermatomyositis. Dermatomyositis (DM) is an idiopathic multi-system inflammatory condition that is of presumed autoimmune pathogenesis1. It classically presents with a symmetric, proximal, extensor inflammatory myopathy and a characteristic cutaneous eruption. Dermatomyositis has a bimodal age distribution, with both adult and juvenile forms. The pathogenesis is believed to be a result of an immune mediated process triggered by external factors (malignancy, infectious agents) in genetically predisposed individuals1. Additionally, the interferon pathway has recently been implicated as critical in its pathophysiology2. Serum antinuclear autoantibodies are often present which further supports an autoimmune etiology. The cutaneous features include pathognomonic findings of Gottron’s papules (pink to violaceous papules on dorsal hands) and heliotrope eruption (pink-violaceous erythema involving the upper eyelids). Other findings include poikiloderma of the upper back (“shawl” sign) and upper chest, nailfold abnormalities (periungal erythema, dilated capillary nail bed loops) as well as scaly erythema of the lateral thighs (holster sign) and scalp involvement3. In juvenile DM, calcinosis cutis is common, particular on the extensor surfaces1. When evaluating muscle disease, a detailed history assessing proximal muscle groups as well as strength testing should be performed. Cutaneous disease precedes the appearance of myositis by 3-6 months in almost 50% of cases while 10% have myositis prior to any skin findings3. Importantly, DM exists on a spectrum where either skin or muscle phenotype can predominate and can also present as amyopathic. Diagnosis is often made clinically without a skin biopsy however it may be helpful if exam findings are subtle or atypical. Histopathology shows an interface dermatitis with dermal mucin deposition, which would be indistinguishable from lupus erythematosus3. Myositis specific autoantibodies in recent years have been helpful in identifying associated phenotypes. Anti-Mi-2 is associated with both adult and juvenile DM, with milder muscle disease and a good response to treatment1. Anti-MDA5 is associated with rapidly progressive interstitial lung disease and cutaneous ulcerations3. Anti-TIF-1 gamma and Anti-NXP-2 are most closely associated with malignancy3. Once DM is diagnosed, additional work up is required including but not limited to serum CK/aldolase, EMG or MRI of muscle, pulmonary function tests (answer choice A), EKG/echocardiogram (answer choice E) and barium swallow or manometry1. Dermatomyositis and its association with malignancy is well known, with a recent study showing the risk to be 6x higher than the general population4.  Most common malignancies include ovarian, colon, breast, lung, hematopoietic and nasopharyngeal cancer, particularly in Asian populations5. Although no specific guidelines exist, initial work up includes CBC, CMP and UA as well as chest x-ray and age-appropriates screening. CT chest/abdomen/pelvis (answer choice C) is typically performed if the initial work up is worrisome or in patients that are considered high risk. CA 125 and CA 19-9 (answer choice B) can be considered based on individual patient risk factors. Brain MRI (answer choice D) is not routinely part of the work up as brain neoplasms/malignancies are not strongly associated with DM. Treatment includes skin directed therapy with topical steroids, calcineurin inhibitors and photoprotection1. Historically for patients with severe disease, first line therapy included systemic steroids plus disease modifying antirheumatic drugs such as methotrexate, azathioprine, or mycophenolate mofetil2. However, IVIG was recently FDA approved for DM and has shown to be very effective regardless of disease severity6. Rituximab or cyclophosphamide are sometimes added, particularly when there is lung or severe muscle involvement7.  Apremilast has been shown to help with recalcitrant disease and can be considered as an adjunct treatment8. JAK inhibitors as well as more targeted therapy (anti-IFN antibodies) will likely play a more substantial role in the future 9,.10.

Incorrect answer choices

(choice A) – Pulmonary complications are a well-known cause of morbidity and mortality in dermatomyositis and are a critical part of the work up.

(choice B) – CA19-9 screens for pancreatic cancer and is sometimes indicated as part of the work up based on patient risk factors.

(choice C) – CT chest/abdomen/pelvis is often indicated in adult patients to evaluate for malignancy.

(choice E) – EKG or echocardiogram is performed as conduction defects or other arrhythmias can be seen and do not always present with symptoms.

References

    1. Bolognia, J., Schaffer, J., & Cerroni, L. (2018). Dermatology (Fourth edition.). Philadelphia,Pa: Elsevier.
    2. Bolko L, Jiang W, Tawara N, Landon-Cardinal O, Anquetil C, Benveniste O, Allenbach Y. The role of interferons type I, II and III in myositis: A review. Brain Pathol. 2021 May;31(3):e12955. doi: 10.1111/bpa.12955. PMID: 34043262; PMCID: PMC8412069.
    3. Cobos GA, Femia A, Vleugels RA. Dermatomyositis: An Update on Diagnosis and Treatment. Am J Clin Dermatol. 2020 Jun;21(3):339-353. doi: 10.1007/s40257-020-00502-6. PMID: 32096127.
    4. Hu T, Vinik O. Dermatomyositis and malignancy. Can Fam Physician. 2019 Jun;65(6):409-411. PMID: 31189628; PMCID: PMC6738379.
    5. Leatham H, Schadt C, Chisolm S, Fretwell D, Chung L, Callen JP, Fiorentino D. Evidence supports blind screening for internal malignancy in dermatomyositis: Data from 2 large US dermatology cohorts. Medicine (Baltimore). 2018 Jan;97(2):e9639. doi: 10.1097/MD.0000000000009639. PMID: 29480875; PMCID: PMC5943873.
    6. Werth VP, Aggarwal R, Charles-Schoeman C, Schessl J, Levine T, Kopasz N, Worm M, Bata-Csörgő Z. Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study. EClinicalMedicine. 2023 Oct 2;64:102234. doi: 10.1016/j.eclinm.2023.102234. PMID: 37799613; PMCID: PMC10550512.
    7. (n.d.). Retrieved April 10,2024, from https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-dermatomyositis-and-polymyositis-in-adults.
    8. Bitar C, Ninh T, Brag K, Foutouhi S, Radosta S, Meyers J, Baddoo M, Liu D, Stumpf B, Harms PW, Saba NS, Boh E. Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022 Dec 1;158(12):1357-1366. doi: 10.1001/jamadermatol.2022.3917. PMID: 36197661; PMCID: PMC9535502.
    9. Paik JJ, Lubin G, Gromatzky A, Mudd PN Jr, Ponda MP, Christopher-Stine L. Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review. Clin Exp Rheumatol. 2023 Mar;41(2):348-358. doi: 10.55563/clinexprheumatol/hxin6o. Epub 2022 Jun 28. PMID: 35766013; PMCID: PMC10105327.
    10. Aggarwal, R., Domyslawska, I., Carreira, P., Fiorentino, D., Sluzevich, J., Werth, V., Banerjee, A., Chu, M., Oemar, B., Salganik, M., Sloan, A., Vincent, M., & Peeva, E. (2023, June 1).POS1207 efficacy and safety of ANTI-IFNΒ-SPECIFIC monoclonal antibody, PF-06823859, on myositis: Phase 2 study in patients with moderate-to-severe dermatomyositis. Annals of the Rheumatic Diseases. https://ard.bmj.com/content/82/Suppl_1/936.1.citation-tools

March 2024 Case Study

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March 2024 Case Study

Authors: Cleo Whiting, BA1, Emily Murphy, MD1, Karl Saardi, MD1

  1. Department of Dermatology, George Washington University School of Medicine and Health Sciences

A 57-year-old female with a past medical history of hypertension presented with numerous pink to skin-colored, soft, mildly tender papules and nodules on the right posterior shoulder, upper arm, and forearm (figure 1A and 1B) that appeared 15 years ago. She also complained of several deeper and larger growths on the bilateral thighs and left hip that appeared a few years ago. A shave biopsy of one of the papules was performed (figure 2A and 2B, hematoxylin-eosin staining). Immunohistochemistry was positive for S100 and negative for smooth muscle actin. A buccal swab was obtained for sequencing of the NF1 gene and the results were negative for pathogenic mutations.

Based on the clinical presentation and biopsy findings, what risks should the patient be counseled about?

A.) None, reassurance only
B.) Risk of renal cell carcinoma
C.) Risk of malignant peripheral nerve sheath tumor
D.) Potential inheritance of condition by offspring
E.) B & D
F.) C & D

         

 

Correct Answer: F

Explanation/Literature review:

Given the segmental distribution of biopsy-confirmed neurofibromas and negative genetic testing, the patient was diagnosed with mosaic neurofibromatosis type 1 (NF1). Also referred to as segmental or localized NF1, this condition results from a post-zygotic pathogenic mutation in one copy of the NF1 gene.1 Mosaic NF1 is a rare, heterogeneous disorder characterized by localized cutaneous or neural findings typical of generalized NF1, such as neurofibromas, intertriginous freckling, and multiple, large cafe-au-lait macules.2 The affected NF1 gene encodes for the tumor suppressor protein neurofibromin, a GTPase-activating protein that regulates the RAS-MAPK pathway; biallelic loss of function of NF1 leads to the development of neurofibromas and other NF1-associated tumors.3

There are no specific guidelines for the management of mosaic NF1, although individuals with this condition may experience complications typical of generalized NF1, including the transformation of plexiform neurofibromas to malignant peripheral nerve sheath tumors (MPNSTs) (choice C), so reassurance alone is not appropriate (choice A).2,4,5 Although rare, gonadal mosaicism is also possible and offspring of the individual can acquire generalized NF1 (choice D).5 The diagnostic criteria for mosaic NF1 have been recently re-established, and revealing NF1 mutations in affected skin, but not in seemingly unaffected tissues like saliva and blood, is one way to make the diagnosis.6

While individuals with mosaic NF1 have an increased risk of malignancy during their lifetime, renal cell carcinoma is associated with hereditary leiomyomatosis and renal cell cancer [HLRCC], also known as Reed syndrome,7 and neurofibromatosis type 2 (choice B, E).8 Characterized by cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma, HLRCC is caused by a pathogenic mutation in the fumarate hydratase gene and inherited in an autosomal dominant pattern with variable penetrance.7

References

  1. Tinschert S, Naumann I, Stegmann E, et al. Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene. Eur J Hum Genet. 2000;8(6):455-459. doi:10.1038/sj.ejhg.5200493
  2. Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. Neurology. 2001;56(11):1433-1443. doi:10.1212/wnl.56.11.1433
  3. Maertens O, De Schepper S, Vandesompele J, et al. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet. 2007;81(2):243-251. doi:10.1086/519562
  4. Stewart DR, Korf BR, Nathanson KL, Stevenson DA, Yohay K. Care of adults with neurofibromatosis type 1: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018;20(7):671-682. doi:10.1038/gim.2018.28
  5. García-Romero MT, Parkin P, Lara-Corrales I. Mosaic Neurofibromatosis Type 1: A Systematic Review. Pediatr Dermatol. 2016;33(1):9-17. doi:10.1111/pde.12673
  6. Legius E, Messiaen L, Wolkenstein P, et al. Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med. 2021;23(8):1506-1513. doi:10.1038/s41436-021-01170-5
  7. Scharnitz T, Nakamura M, Koeppe E, et al. The spectrum of clinical and genetic findings in hereditary leiomyomatosis and renal cell cancer (HLRCC) with relevance to patient outcomes: a retrospective study from a large academic tertiary referral center. Am J Cancer Res. 2023;13(1):236-244. Published 2023 Jan 15.
  8. Paintal A, Tjota MY, Wang P, et al. NF2-mutated Renal Carcinomas Have Common Morphologic Features Which Overlap With Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma: A Comprehensive Study of 14 Cases. Am J Surg Pathol. 2022;46(5):617-627. doi:10.1097/PAS.0000000000001846

February 2024 Case Study

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February 2024 Case Study

Authors: Nagasai Adusumilli, MD, MBA1

1. Department of Dermatology, The George Washington University School of Medicine and Health Sciences

A 75-year-old male with a medical history of metastatic renal cell carcinoma, undergoing treatment with multiple systemic therapies, presented with 3 weeks of pink lesions on his hands, feet, and scrotum, with exquisite pain limiting ability to hold a pen and ambulate. Findings on the hands and feet are shown in Figure 1, and scrotal findings are shown in Figure 2. Notably, mucosa of the eyes, nose, mouth, urethral meatus, and anus were not involved. The patient experienced symptomatic improvement with 2 days of high potency topical corticosteroids and topical keratolytics.

Based on the clinical presentation, which of the following categories of medications has been most extensively implicated for this drug reaction?

A.) PD-1 inhibitors
B.) Beta-lactam antibiotics
C.) Aromatic anticonvulsants
D.) Sulfonamides
E.) Multikinase inhibitors

 

                   

Correct Answer: E.) Multikinase inhibitors

Explanation of Correct Answer:

This patient’s clinical history and findings of multiple tender, pink-red thin macules and patches with a dusky center in the interdigital spaces of the hands, on the palmar surfaces of the fingers, and on the heels of the feet, along with scrotal desquamation, were consistent with hand-foot skin reaction (HFSR) and scrotal erythema, secondary to axitinib, a tyrosine kinase inhibitor of the vascular endothelial growth factor (VEGF) pathway. HFSR is classically characterized by discrete, exquisitely painful lesions with a halo of erythema, and hyperkeratotic lesions localized to sites of high contact, friction, and pressure, such as tips of fingers and toes, skin overlying metacarpophalangeal or interphalangeal joints, and heels.1,2 HFSR tends to develop within 2-4 weeks of starting multikinase inhibitors, such as sorafenib, sunitinib, cabozantinib, and axitinib (choice E), with pain that can impair range of motion, weight bearing, and overall function.1,2 Although scrotal involvement secondary to multikinase inhibitors is not as common, scrotal erythema, desquamation, and even ulceration have been reported.3

As newer immunotherapies and small molecule inhibitors are increasingly approved for more indications, identifying common and distinct drug reactions is integral to dermatology. Although skin reactions to any medication can be varied and atypical for individual patients, the morphology can be the key to diving deeper into the medical history to pinpoint the culprit, particularly as comorbidities and polypharmacy increase. Adverse skin eruptions from programmed cell death protein 1 (PD-1) inhibitors (choice A), such as pembrolizumab and nivolumab, more frequently present as morbilliform dermatoses, pruritus, lichenoid eruptions, psoriasiform dermatitis, and bullous pemphigoid.4 Although beta-lactam antibiotics encompass many medications, such as penicillins, cephalosporins, carbapenems, and monobactams, with a wide range of clinical presentations for drug reactions, the class overall is one of the most common causes of acute generalized exanthematous pustulosis5 (choice B). Aromatic anticonvulsants, such as phenytoin, carbamazepine, and phenobarbital (choice C) are commonly implicated in drug induced hypersensitivity syndrome (DIHS), previously drug reaction with eosinophilia and systemic symptoms (DRESS), and in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).5 Similarly, drug reactions from sulfonamides (choice D) have multiple possible presentations, but exanthematous eruption, fixed drug eruption, and SJS/TEN are the most characteristic.5

HFSR is often used interchangeably with palmoplantar erythrodysthesia, or hand-foot syndrome, which was initially described as a subset of toxic erythema of chemotherapies, such as taxanes, cytarabine, capecitabine, anthracyclines, and systemic 5-fluorouracil. Although HFSR can clinically appear similar to hand-foot syndrome, they are separate drug reactions, with the localized hyperkeratotic lesions with a rim of erythema distinct from the symmetric erythema, edema, paresthesia, and dysesthesia seen with hand-foot syndrome from cytotoxic chemotherapies. A high density of eccrine glands is thought to drive the skin manifestations of hand-foot syndrome5 whereas inhibited vascular repair mechanisms in fibroblasts and endothelial cells via VEGF and platelet-derived growth receptor (PDGFR) are hypothesized to predispose areas of trauma to HFSR.6 In fact VEGF and PDGFR inhibitors, such as sorafenib, sunitinib, cabozantinib, and axitinib are among the multikinase inhibitors reported to cause HFSR.1,3,6

Contrary to the nomenclature, the tender erythematous patches and plaques are not limited to just the hands and feet. Flexural surfaces and bony prominences can also be affected. Identifying that each figure of this case illustrates areas of high friction or pressure is key to clinching the diagnosis, even without knowing the specific medications that can treat metastatic renal cell carcinoma. Grading the severity of cutaneous adverse events dictates the overall management strategy.7 Because these symptoms are limiting self-care activities of daily living, this patient has a grade 3 cutaneous adverse event,7 warranting collaboration with oncology colleagues to consider dose reduction, discontinuation, or temporary cessation of the causative anticancer agent.1 In the interim, high potency topical corticosteroids and topical keratolytics, such as urea cream, may provide symptomatic relief.1,8

References:

  1. Lacouture ME, Wu S, Robert C, at al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008 Sep;13(9):1001-11. PMID: 18779536.
  2. Kaul S, Kaffenberger BH, Choi JN, Kwatra SG. Cutaneous adverse reactions of anticancer agents. Dermatol Clin. 2019 Oct;37(4):555-568. PMID: 3146695.
  3. Zuo RC, Apolo AB, DiGiovanna JJ, et al. Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib. JAMA Dermatol. 2015 Feb;151(2):170-7. PMID: 25427282.
  4. Adusumilli NC, Friedman AJ. Treating cutaneous immune-related adverse events from immune checkpoint blockade. J Drugs Dermatol. 2021 Oct 1;20(10):1133-1134. PMID: 34636526.
  5. Valeyrie-Allanore L, Obeid G, Revuz J. Chapter 21 – Drug Reactions. In: Dermatology. Fourth Edition. Elsevier; 348-375.
  6. Fischer A, Wu S, Ho AL, Lacouture ME. The risk of hand-foot skin reaction to axitinib, a novel VEGF inhibitor: a systematic review of literature and meta-analysis. Investigational new drugs. 2013;31(3):787-797. PMID: 23345001.
  7. NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 data files. 2017. https://evs.nci.nih.gov/ftp1/CTCAE/About.html. Accessed 20 Jan 2024.
  8. Ren Z, Zhu K, Kang H, et al. Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2015 Mar 10;33(8):894-900. PMID: 25667293.