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More than skin deep
YAJEM-57571; No of Pages 2 American Journal of Emergency Medicine xxx (2018) xxx–xxx
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
More than skin deep☆ Constanza Riquelme-Mc Loughlin, MD, Priscila Giavedoni, MD, José M. Mascaró Jr, MD ⁎ Department of Dermatology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
a r t i c l e
i n f o
Article history: Received 27 May 2018 Accepted 29 May 2018 Available online xxxx Keywords: Methotrexate Intoxication Pancytopenia Mucositis Psoriasis
a b s t r a c t We present the case of a woman in her 50s with past medical history significant for psoriasis treated with methotrexate on a stable dose for the past 20 years, diabetes mellitus and chronic kidney disease. In the setting of a long flight, dehydration and non steroidal anti-inflammatory drug consumption, the patient presented to the emergency department with oral mucositis and cutaneous erosions and ulcers of the psoriasis plaques. MTX levels were normal corroborated by three different measurements in 24 h. Initially the complete blood count tests were significant for macrocytic, thrombocytopenia (82.000 103/L) and impaired kidney function. The patient was diagnosed of acute methotrexate toxicity and started on intravenous folinic acid. In 24 h the patient developed severe pancytopenia. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10 days, the CBC improved to normal levels and the cutaneous lesions resolved. © 2018 Elsevier Inc. All rights reserved.
We present the case of a woman in her 50s, with psoriasis diagnosed on her 20s treated with 25 mg of methotrexate (MTX) with weekly oral folic acid supplements, on the same MTX prescription dose for the past 20 years. She also had a PMH significant for diabetes mellitus with associated stage 2 chronic kidney disease (CKD). After a 15-h flight, the patient complained of pain on her psoriasis plaques, for which she took 600 mg of ibuprofen and of odynophagia decreasing oral intake. She consulted a general practitioner that prescribed amoxicillin/clavulanic acid 875/125 mg every 8 h. The patient consulted the emergency department within 48 h due to ulcerations of the oral mucosa (Fig. 1) and all of her psoriasis plaques (Fig. 2). Complete blood count (CBC) tests were significant for macrocytic anemia (hemoglobin 7.5 g/L, mean corpuscular volume (MCV) 103.8 fL), thrombocytopenia (82.000 103/L) and impaired kidney function (creatinine of 5 mg/dL, glomerular filtration rate of 9.48 mL/min/1.73m2). Due to the characteristic medical presentation and CBC results, the patient was diagnosed of acute MTX toxicity in the clinical setting of acute on CKD due to dehydration and nonsteroidal anti-inflammatory drug (NSAID) intake. She was started on initial doses of 75 mg/m2 intravenous folinic acid. MTX levels were normal (b0.3 μmol/L) corroborated by three different measurements in 24 h. Although the initial leukocyte count was normal, within 24 h she developed severe neutropenia with
Abbreviations: CKD, chronic kidney disease; CBC, complete blood count; MCV, mean corpuscular volume; MTX, methotrexate; NSAID, nonsteroidal anti-inflammatory drug. ☆ This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. ⁎ Corresponding author at: C/de Villarroel 170, 08036 Barcelona, Spain. E-mail address: [email protected] (J.M. Mascaró).
neutrophil counts below 100 103/L. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10 days, the CBC improved to normal levels and the cutaneous lesions resolved. The patient was discharged from the hospital after 13 days since her admission. Oral mucositis and cutaneous erosions and ulcers, particularly on psoriasis plaques, and pancytopenia are characteristic clinical findings in patients developing severe acute MTX toxicity [1]. MTX inhibits cells with a fast turnover, such as hematopoietic, gastrointestinal and cutaneous cells, which are mitotically more active and more prone to
Fig. 1. Oral mucositis on arrival to the emergency department.
https://doi.org/10.1016/j.ajem.2018.05.069 0735-6757/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: Riquelme-Mc Loughlin C, et al, More than skin deep, American Journal of Emergency Medicine (2018), https://doi.org/ 10.1016/j.ajem.2018.05.069
2
C. Riquelme-Mc Loughlin et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
intake of drugs such as NSAIDs, cyclosporine and certain antibiotics such as co-trimoxazole or amoxicillin/clavulanic acid can alter renal function and increase MTX accumulation. The half-life of MTX is approximately 6 to 8 h in healthy individuals, and plasma concentrations are usually b0.01 μM by 24 h after drug withdrawal [4]. Therefore, a negative MTX level should not deviate from the suspicion of acute MTX toxicity if other clinical signs are present. Clinicians must know the alert signs of acute MTX toxicity, such as mucocutaneous ulcerations, mucositis or elevated MCV, and treat the intoxication accordingly. Conflict of interest disclosures None reported. Fig. 2. Painful erosions and ulceration of psoriasis plaques on the abdomen.
References be affected by the anti-proliferative effect of MTX [2]. Elevated MCV, may indicate folate depletion, which can be an early sign of bone marrow intoxication. This is important, because the most common severe side effect associated with MTX is bone marrow toxicity, which is found in 2.5–10% of patients, and is potentially lethal [3]. Pancytopenia is usually dose related and can be observed in patients who were unintentionally taking MTX on a daily basis, patients with CKD, elderly patients or patients taking concomitant medications [4]. Renal insufficiency can increase MTX toxicity because its elimination depends on glomerular filtration and tubular secretion. In addition, concomitant
[1] Fridlington DD, Jl Tripple JW, Reichenberg JS, Hall CS. Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: a diagnostic clue. Dermatol Online J 2011;17:2. [2] Bookstaver FJ, Pb Norris L, Rudisill C, DeWitt T, Aziz S. Multiple toxic effects of lowdose methotrexate in a patient treated for psoriasis. Am J Health Syst Pharm 2008; 65:2117–21. [3] Haustein RM. UF, methotrexate in psoriasis: 26 years' experience with low-dose longterm treatment. J Eur Acad Dermatol Venereol 2000;14:382–8. [4] Chen TJ, Chung WH, Chen CB, Hui RCY, Huang YH, Lu YT, Wang CW, Wang KH, Yang LC, Hung SI. Methotrexate-induced epidermal necrosis: a case series of 24 patients. J Am Acad Dermatol 2017;77:247–55.
Please cite this article as: Riquelme-Mc Loughlin C, et al, More than skin deep, American Journal of Emergency Medicine (2018), https://doi.org/ 10.1016/j.ajem.2018.05.069
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
More than skin deep☆ Constanza Riquelme-Mc Loughlin, MD, Priscila Giavedoni, MD, José M. Mascaró Jr, MD ⁎ Department of Dermatology, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
a r t i c l e
i n f o
Article history: Received 27 May 2018 Accepted 29 May 2018 Available online xxxx Keywords: Methotrexate Intoxication Pancytopenia Mucositis Psoriasis
a b s t r a c t We present the case of a woman in her 50s with past medical history significant for psoriasis treated with methotrexate on a stable dose for the past 20 years, diabetes mellitus and chronic kidney disease. In the setting of a long flight, dehydration and non steroidal anti-inflammatory drug consumption, the patient presented to the emergency department with oral mucositis and cutaneous erosions and ulcers of the psoriasis plaques. MTX levels were normal corroborated by three different measurements in 24 h. Initially the complete blood count tests were significant for macrocytic, thrombocytopenia (82.000 103/L) and impaired kidney function. The patient was diagnosed of acute methotrexate toxicity and started on intravenous folinic acid. In 24 h the patient developed severe pancytopenia. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10 days, the CBC improved to normal levels and the cutaneous lesions resolved. © 2018 Elsevier Inc. All rights reserved.
We present the case of a woman in her 50s, with psoriasis diagnosed on her 20s treated with 25 mg of methotrexate (MTX) with weekly oral folic acid supplements, on the same MTX prescription dose for the past 20 years. She also had a PMH significant for diabetes mellitus with associated stage 2 chronic kidney disease (CKD). After a 15-h flight, the patient complained of pain on her psoriasis plaques, for which she took 600 mg of ibuprofen and of odynophagia decreasing oral intake. She consulted a general practitioner that prescribed amoxicillin/clavulanic acid 875/125 mg every 8 h. The patient consulted the emergency department within 48 h due to ulcerations of the oral mucosa (Fig. 1) and all of her psoriasis plaques (Fig. 2). Complete blood count (CBC) tests were significant for macrocytic anemia (hemoglobin 7.5 g/L, mean corpuscular volume (MCV) 103.8 fL), thrombocytopenia (82.000 103/L) and impaired kidney function (creatinine of 5 mg/dL, glomerular filtration rate of 9.48 mL/min/1.73m2). Due to the characteristic medical presentation and CBC results, the patient was diagnosed of acute MTX toxicity in the clinical setting of acute on CKD due to dehydration and nonsteroidal anti-inflammatory drug (NSAID) intake. She was started on initial doses of 75 mg/m2 intravenous folinic acid. MTX levels were normal (b0.3 μmol/L) corroborated by three different measurements in 24 h. Although the initial leukocyte count was normal, within 24 h she developed severe neutropenia with
Abbreviations: CKD, chronic kidney disease; CBC, complete blood count; MCV, mean corpuscular volume; MTX, methotrexate; NSAID, nonsteroidal anti-inflammatory drug. ☆ This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. ⁎ Corresponding author at: C/de Villarroel 170, 08036 Barcelona, Spain. E-mail address: [email protected] (J.M. Mascaró).
neutrophil counts below 100 103/L. She required treatment with colony-stimulating factors, platelet and blood transfusions. After 10 days, the CBC improved to normal levels and the cutaneous lesions resolved. The patient was discharged from the hospital after 13 days since her admission. Oral mucositis and cutaneous erosions and ulcers, particularly on psoriasis plaques, and pancytopenia are characteristic clinical findings in patients developing severe acute MTX toxicity [1]. MTX inhibits cells with a fast turnover, such as hematopoietic, gastrointestinal and cutaneous cells, which are mitotically more active and more prone to
Fig. 1. Oral mucositis on arrival to the emergency department.
https://doi.org/10.1016/j.ajem.2018.05.069 0735-6757/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: Riquelme-Mc Loughlin C, et al, More than skin deep, American Journal of Emergency Medicine (2018), https://doi.org/ 10.1016/j.ajem.2018.05.069
2
C. Riquelme-Mc Loughlin et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
intake of drugs such as NSAIDs, cyclosporine and certain antibiotics such as co-trimoxazole or amoxicillin/clavulanic acid can alter renal function and increase MTX accumulation. The half-life of MTX is approximately 6 to 8 h in healthy individuals, and plasma concentrations are usually b0.01 μM by 24 h after drug withdrawal [4]. Therefore, a negative MTX level should not deviate from the suspicion of acute MTX toxicity if other clinical signs are present. Clinicians must know the alert signs of acute MTX toxicity, such as mucocutaneous ulcerations, mucositis or elevated MCV, and treat the intoxication accordingly. Conflict of interest disclosures None reported. Fig. 2. Painful erosions and ulceration of psoriasis plaques on the abdomen.
References be affected by the anti-proliferative effect of MTX [2]. Elevated MCV, may indicate folate depletion, which can be an early sign of bone marrow intoxication. This is important, because the most common severe side effect associated with MTX is bone marrow toxicity, which is found in 2.5–10% of patients, and is potentially lethal [3]. Pancytopenia is usually dose related and can be observed in patients who were unintentionally taking MTX on a daily basis, patients with CKD, elderly patients or patients taking concomitant medications [4]. Renal insufficiency can increase MTX toxicity because its elimination depends on glomerular filtration and tubular secretion. In addition, concomitant
[1] Fridlington DD, Jl Tripple JW, Reichenberg JS, Hall CS. Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: a diagnostic clue. Dermatol Online J 2011;17:2. [2] Bookstaver FJ, Pb Norris L, Rudisill C, DeWitt T, Aziz S. Multiple toxic effects of lowdose methotrexate in a patient treated for psoriasis. Am J Health Syst Pharm 2008; 65:2117–21. [3] Haustein RM. UF, methotrexate in psoriasis: 26 years' experience with low-dose longterm treatment. J Eur Acad Dermatol Venereol 2000;14:382–8. [4] Chen TJ, Chung WH, Chen CB, Hui RCY, Huang YH, Lu YT, Wang CW, Wang KH, Yang LC, Hung SI. Methotrexate-induced epidermal necrosis: a case series of 24 patients. J Am Acad Dermatol 2017;77:247–55.
Please cite this article as: Riquelme-Mc Loughlin C, et al, More than skin deep, American Journal of Emergency Medicine (2018), https://doi.org/ 10.1016/j.ajem.2018.05.069