Commentary - Journal of Experimental Neurology (2020) Volume 1, Issue 4
Cutaneous Side Effects of First-Second Line Oral Disease - Modifying Treatments in Patients with Multiple Sclero
Doruk Arslan*, Asli Tuncer
Department of Neurology, School of Medicine, University of Hacettepe, Ankara, Turkey
- *Corresponding Author:
- Doruk Arslan
Received date: June 06, 2020; Accepted date: December 03, 2020
Citation: Arslan D, Tuncer A. Cutaneous Side Effects of First / Second Line Oral Disease - Modifying Treatments in Patients with
Multiple Sclerosis. J Exp Neurol. 2020;1(4): 152-157.
Copyright: © 2020 Arslan D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Multiple sclerosis (MS) is a progressive autoimmune and sometimes disabling disease of the central nervous system (CNS), characterized
by formation of white matter lesions in the CNS due to inflammation, demyelination and axonal loss. Disease-modifying treatments
(DMTs) are being investigated as a treatment choice in patients with MS. Teriflunomide, fingolimod and dimethyl fumarate are the
most popular oral forms of the DMTs that are used usually for relapsing forms of MS (RMS), the most common disease phenotype. In
this complementary, we have compiled the reports about cutaneous adverse reactions associated with oral first or second line DMTs.
There have been recently published rare cases to point out serious cutaneous adverse effects associated with fingolimod therapy such
as Kaposi sarcoma, peripheral vascular adverse effects, ecchymotic angioedema-like cutaneous lesions, lymphomatoid papulosis.
There are also a few case reports about cutaneous adverse effects of teriflunomide, such as eczema, rash and palmar pustular psoriasis.
In addition, a recently published case report has demonstrated another serious adverse effect associated with teriflunomide; drug –
induced bullous pemphigoid. However, there aren’t many reported skin changes associated with dimethyl fumarate use in patients
with MS, just a newly reported case report about transient hair loss. By examining the specific clinical, pharmacological and safety
features of all drugs, we tried to provide an overview. In addition, it is important to point out some immunosuppressants may trigger
autoimmune diseases. These DMTs may also have led to similar autoimmune phenomenon, attending to the development of some
cutaneous autoimmune reactions. The molecular mechanisms behind these reactions are still unknown and further studies are
needed to reveal them.
Multiple Sclerosis, Teriflunomide, Fingolimod, Dimethyl fumarate, Cutaneous adverse effects
Multiple sclerosis (MS) is a progressive autoimmune and sometimes disabling disease of the central nervous system (CNS), characterized by formation of white matter lesions in the CNS due to inflammation, demyelination and axonal loss [1-3]. However, the disease also affects gray matter as well as white matter, and possibly this effect is related to irreversible disability and progressive symptoms. MS is the second most common cause of disability in young adults. It appears as a result of genetic and environmental factors that serve as activators of the immune response. The age of onset is generally between the mid to late 20s, while the female/male ratio is about 3:1 [4-6].
When the pathophysiology of the disease is reviewed, the migration of inflammatory cells to the CNS, through the blood-brain barrier, shows the first mechanism of disease formation. This inflammation causes white matter lesions or plaques and usually these white matter lesions tend to be noticeable in highly myelinated areas. The most common affected areas are optic nerves, periventricular and subcortical white matter and descending traces in the pons, and midbrain. The spinal cord is also often affected. Depending on their location in the CNS, these lesions typically manifest as symptomatic ‘attacks’ and indicate ‘active’ disease [7-9]. Since MS plaques can occur
in a variety of neuroanatomic locations, patients may
be presented with a wide variety of symptoms. Patients
usually report problems related to ambulation, weakness,
sensory loss, loss of balance, fatigue, depression, memory
loss and urination. However, MS is a very heterogeneous
disease. Each patient with a diagnosis of MS may behave
differently and the severity of the disease may alter in wide
Disease-modifying treatments (DMTs) are being investigated as a treatment choice in patients with MS . Their effect in reducing CNS damage has been proved with lots of clinical trials so far . Teriflunomide, fingolimod and dimethyl fumarate are the most popular oral forms of the DMTs that are used usually for relapsing forms of MS (RMS), the most common disease phenotype . In approximately 85 % of all cases, MS initially manifests as RMS, which is characterized by episodes of neurological worsening followed by partial or total recovery [1,3]. DMTs, all of which have immunomodulatory or immunosuppressive properties, have shown efficacy to improve the course of RMS . Early DMT therapy has been recommended to control clinical and subclinical inflammatory disease activity , but new treatmentrelated risks have also arisen, including immune - related cutaneous side effects, such as drug induced bullous pemphigoid . The various efficacy and safety profiles of DMTs put more emphasis on ‘personalized’ approaches that adapt treatment decisions to the patient’s disease characteristics and preferences . Although all of the mentioned DMTs act through variable immunological mechanisms, all improve the course of RMS as assessed by reductions in annualized relapse rate and MRI outcomes . Before using fingolimod in the treatment of RMS, the disease was treated with injectable drugs. Next, two other oral agents, teriflunomide and dimethyl fumarate were approved for the treatment of RMS.
Fingolimod is the first oral agent approved by the United States Food and Drug Administration (2010) and European Medicines Agency (2011) for maintenance therapy of relapsing–remitting multiple sclerosis. It is a modulator of S1P (sphingosine-1-phosphate) receptor, which is located on the surface of lymphocytes and CNS cells. After phosphorylation, fingolimod phosphate, which is its active form, binds to the S1P receptor. Then, it inhibits the outflow of lymphocytes from the lymph nodes, causing the lymphocytes to redistribute. This redistribution reduces infiltration of pathogenic lymphocytes into the CNS. However, it reduces the potential of the abnormal autoimmune processes to occur. Furthermore, this molecule may also cross the blood-brain barrier and bind to S1P receptors on CNS cells. As a result of lymphocyte retention, the number of peripheral blood lymphocytes decreases during fingolimod therapy. The lymphocyte counts become normal within 1 to 2 months after cessation of treatment. This indicates that the existing effect is reversible and allows the redistribution of lymphocytes to lymphoid tissues [16,17]. The risk-benefit profiles of fingolimod have been specified in one phase II study , three phase III studies and in a long-term follow-up study [19-21]. In addition, post-marketing clinical experience is still being shared. The most common adverse events related to fingolimod (incidence ≥10% and > placebo) found in various clinical trials are headache, influenza, diarrhea, nausea, cough, back pain and elevation of liver enzymes . However, first dose bradycardia or atrioventricular
block formation due to fingolimod use are known in
some patients, hence vital signs and electrocardiograms
must be monitored clinically before and after the first
dose is administered. Apart from the first dose effect
of the drug, there are also some other well-known side
effects associated with fingolimod including QT interval
prolongation, hypertension, macular edema, pulmonary
toxicity, and possibly hepatotoxicity. It is also important
to point out that 18 patients treated with fingolimod have
developed progressive multifocal leukoencephalopathy,
including 3 patients without prior natalizumab exposure
[23,24]. Although some certain adverse events exist
among the patients including some cardiac abnormalities,
macular edema, some hepatic laboratory abnormalities
and possible infection risks, there have been recently
published rare cases to point out serious cutaneous
adverse effects associated with fingolimod therapy such as
Kaposi sarcoma , peripheral vascular adverse effects
, ecchymotic angioedema-like cutaneous lesions ,
lymphomatoid papulosis . Fingolimod has increased
the risk of varicella zoster virus infection compared to
placebo in clinical trials. Fatal disseminated varicella
zoster virus  and herpes simplex virus-1 infections
 have occurred. Cryptococcal central nervous system
and skin infections have also been reported [31,32].
There is also a temporal association between fingolimod
exposure and immune thrombocytopenic purpura (ITP),
however dose–effect association or pathogenesis is still
unclear . Furthermore, skin cancers including basal
cell carcinoma, squamous cell carcinoma and melanoma
have been reported in the clinical trials [21,34].
Teriflunomide is the second oral agent approved by the United States Food and Drug Administration (2012) and European Medicines Agency (2013) for maintenance therapy of relapsing–remitting multiple sclerosis. The drug reversibly inhibits dihydro-orotate dehydrogenase, an enzyme in de novo pyrimidine synthesis and facilitates a contrary effect on proliferation of activated T and B lymphocytes  limiting their contribution to MS pathogenesis . Oral daily therapy of Teriflunomide has shown efficacy on disability, annualized relapse rate, and magnetic resonance imaging markers of disease in patients with RMS, and in those with a first clinical episode of suggestive MS [35-38]. The safety analysis of teriflunomide-treated patients was obtained from three placebo-controlled trials: TEMSO, TOWER, and TOPIC [35-37]. Adverse events reported in 10 % of patients treated with teriflunomide were diarrhea, nausea, increased alanine aminotransferase, headache and hair thinning . Minor reductions in white blood cells have been observed in patients receiving teriflunomide in clinical trials. No increase in the incidence of serious infections has been observed with teriflunomide. There has been no increased risk of malignancy with teriflunomide treatment. Peripheral neuropathy, including both polyneuropathy and mononeuropathy has been reported. There aren’t many reported skin changes associated with teriflunomide use in patients with MS. Only one life-threatening gross skin change has been reported so far; a patient with toxic epidermal necrolysis (TEN) . There are also a few case
reports about cutaneous adverse effects of teriflunomide,
such as eczema, rash and palmar pustular psoriasis [40-43]. In addition, a recently published case report has
demonstrated another serious adverse effect associated
with teriflunomide; drug – induced bullous pemphigoid
. Totally five cases of teriflunomide associated
cutaneous drug reactions can be found in literature search
via PubMed. Psoriasiform changes were mentioned in 2 of
the cases after drug use. The other associated skin changes
were drug – induced bullous pemphigoid, nail loss and
toxic epidermal necrolysis. Considering recently reported
skin reactions associated with teriflunomide, neurologists
and patients should be aware of warning signs and
symptoms that might be associated with a cutaneous drug
reaction caused by this drug.
Dimethyl fumarate is the third oral agent approved by the United States Food and Drug Administration (2013) and European Medicines Agency (2014) for maintenance therapy of relapsing–remitting multiple sclerosis. Dimethyl fumarate has been studied for its effects since 1959 . The exact mode of action of this drug remains a topic of discussion, but it is known that dimethyl fumarate acts on the nuclear factor-like-2 (Nrf2) pathway and has immunomodulatory effects . The efficacy and safety of dimethyl fumarate were investigated in two large randomized, placebo-controlled Phase III studies DEFINE and CONFIRM. These studies confirmed the efficacy of dimethyl fumarate on relapse rates, and only one of them confirmed it effect on progressive disability [46,47]. It is a safe and efficient drug with no reported
increased risk of infection, including opportunistic
infections and no increased risk of malignancy. The most
common adverse effects are gastrointestinal symptoms
and flushing. These placebo-controlled Phase III studies
have also demonstrated that flushing occurred in 40% of
patients and caused discontinuation in 3% of them. On
the other hand, gastrointestinal effects such as abdominal
pain, diarrhea and nausea, occurred in approximately 12-
18% of patients. Furthermore, an elevation in the level
of hepatic enzymes, increased proteinuria, leukopenia
and progressive multifocal leukoencephalopathy were
observed . There are also some recent reports about
newly noticed rare adverse effects of this drug, including
articular and musculoskeletal pain . There aren’t many
reported skin changes associated with dimethyl fumarate
use in patients with MS, just a newly reported case report
about transient hair loss . In addition, it is important
to point out that this drug is nowadays being used for the
treatment of dermatological diseases such as psoriasis and
bullous pemphigoid [51,52].
We have compiled the reports about cutaneous adverse reactions associated with oral first or second line DMTs. Some of the reports are recently published, thus they may not have created sufficient awareness among neurologists yet. By examining the specific clinical, pharmacological and safety features of all drugs, we tried to provide an overview. In addition, it is important to point out some immunosuppressants may trigger autoimmune diseases. The dysregulation of the immune system with inactivation of regulatory T-cells and stimulation of B-cell clones can be suggested as the main determining factor that leads to the emergence of autoimmune diseases [53,54]. These DMTs may also have led to similar
autoimmune phenomenon, attending to the development
of some cutaneous autoimmune reactions. To summarize,
considering recently reported skin reactions associated
with these drugs, neurologists and patients should be
aware of warning signs and symptoms. The molecular
mechanisms behind these reactions are still unknown and
further studies are needed to reveal them.
|Drugs||Cutaneous Side Effects|
|Fingolimod||Kaposi sarcoma , peripheral vascular adverse effects|
, ecchymotic angioedema-like cutaneous lesions ,
lymphomatoid papulosis , disseminated varicella
zoster virus , herpes simplex virus-1 infections
, cryptococcal skin infections , immune
thrombocytopenic purpura , skin cancers (basal cell
carcinoma, squamous cell carcinoma and melanoma) [21,
|Teriflunomide||Drug – induced bullous pemphigoid , toxic epidermal|
necrolysis , nail loss , palmar pustular psoriasis
, psoriasiform changes of fingernails 
|Dimethyl Fumarate||Transient hair loss |
Table 1: Cutaneous side effects of first/second line oral disease- modifying treatments.
- Bar-Or A, Pachner A, Menguy-Vacheron F, Kaplan J,
Wiendl H. Teriflunomide and its mechanism of action in
multiple sclerosis. Drugs. 2014 Apr 1;74(6):659-74.
- Hauser SL, Oksenberg JR. The neurobiology of multiple
sclerosis: genes, inflammation, and neurodegeneration.
Neuron. 2006 Oct 5;52(1):61-76.
- Trapp BD, Nave KA. Multiple sclerosis: an immune or
neurodegenerative disorder?. Annu. Rev. Neurosci. 2008
Jul 21;31: 247-69.
- Noseworthy JH, Lucchinetti C, Rodriguez M,
Weinshenker BG. Medical progress. Multiple Sclerosis. N
Engl J Med. 2000 Sep 28;343(13):938-52.
- Handel AE, Giovannoni G, Ebers GC, Ramagopalan
SV. Environmental factors and their timing in adultonset
multiple sclerosis. Nature Reviews Neurology. 2010
- Magyari M, Koch-Henriksen N, Pfleger CC, Sørensen
PS. Gender and autoimmune comorbidity in multiple
sclerosis. Multiple Sclerosis Journal. 2014 Aug;
- Loma I, Heyman R. Multiple sclerosis: pathogenesis
and treatment. Current Neuropharmacology. 2011 Sep
- Weissert R. The immune pathogenesis of multiple
sclerosis. Journal of Neuroimmune Pharmacology. 2013
- Lehmann PV, Rottlaender A, Kuerten S. The
autoimmune pathogenesis of multiple sclerosis. Die
Pharmazie-An International Journal of Pharmaceutical
Sciences. 2015 Jan 12;70(1):5-11.
- Vargas DL, Tyor WR. Update on disease-modifying
therapies for multiple sclerosis. Journal of Investigative
Medicine. 2017 Jun 1;65(5):883-91.
- Sospedra M, Martin R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 2005 Apr 23;23: 683-747.
- Wingerchuk DM, Carter JL. Multiple sclerosis: current
and emerging disease-modifying therapies and treatment
strategies. InMayo Clinic Proceedings 2014 Feb 1 (Vol. 89,
No. 2, pp. 225-240). Elsevier.
- Wingerchuk DM, Weinshenker BG. Disease modifying
therapies for relapsing multiple sclerosis. Bmj. 2016 Aug
- Arslan D, Aksakal AB, Erdem Ö, Tuncer MA. A case
of drug-induced bullous pemphigoid associated with
teriflunomide: A patient with relapsing multiple sclerosis.
Multiple Sclerosis and Related Disorders. 2020 May
- Derfuss T. Personalized medicine in multiple sclerosis:
hope or reality? BMC medicine. 2012 Dec 1;10(1):116.
- Chun J, Hartung HP. Mechanism of action of oral
fingolimod (FTY720) in multiple sclerosis. Clinical
neuropharmacology. 2010 Mar;33(2):91.
- Guarnera C, Bramanti P, Mazzon E. Comparison
of efficacy and safety of oral agents for the treatment of
relapsing–remitting multiple sclerosis. Drug Design,
Development and Therapy. 2017;11: 2193.
- Calabresi PA, Radue EW, Goodin D, Jeffery D,
Rammohan KW, Reder AT, et al. Safety and efficacy of
fingolimod in patients with relapsing-remitting multiple
sclerosis (FREEDOMS II): a double-blind, randomised,
placebo-controlled, phase 3 trial. The Lancet Neurology.
2014 Jun 1;13(6):545-56.
- Cohen JA, Khatri B, Barkhof F, Comi G, Hartung HP,
Montalban X, et al. Long-term (up to 4.5 years) treatment
with fingolimod in multiple sclerosis: results from the
extension of the randomised TRANSFORMS study.
Journal of Neurology, Neurosurgery & Psychiatry. 2016
- Khatri B, Barkhof F, Comi G, Hartung HP, Kappos
L, Montalban X, et al. Comparison of fingolimod with
interferon beta-1a in relapsing-remitting multiple
sclerosis: a randomised extension of the TRANSFORMS
study. The Lancet Neurology. 2011 Jun 1;10(6):520-9.
- Lublin F, Miller DH, Freedman MS, Cree BA, Wolinsky
JS, Weiner H, et al. Oral fingolimod in primary progressive
multiple sclerosis (INFORMS): a phase 3, randomised,
double-blind, placebo-controlled trial. The Lancet. 2016
- FDA. 2016; Available from: https://www.accessdata.
- Berger JR, Cree BA, Greenberg B, Hemmer B,
Ward BJ, Dong VM, et al. Progressive multifocal
leukoencephalopathy after fingolimod treatment.
Neurology. 2018 May 15;90(20): e1815-21.
- Chaudhry BZ, Cohen JA, Conway DS. Sphingosine
1-phosphate receptor modulators for the treatment
of multiple sclerosis. Neurotherapeutics. 2017 Oct
- Tully T, Barkley A, Silber E. Kaposi sarcoma in a patient
with relapsing-remitting multiple sclerosis receiving
fingolimod. Neurology. 2015 May 12;84(19):1999-2001.
- Russo M, Guarneri C, Mazzon E, Sessa E, Bramanti
P, Calabrò RS. Fingolimod-associated peripheral vascular
adverse effects. InMayo Clinic Proceedings 2015 Oct 1
(Vol. 90, No. 10, pp. 1424-1427). Elsevier.
- Masera SI, Chiavazza C, Mattioda A, Superti G,
Beggiato E, Crosasso P, et al. Occurrence of ecchymotic
angioedema-like cutaneous lesions as a possible side
effect of fingolimod. Multiple Sclerosis Journal. 2014 Oct
- Samaraweera AP, Cohen SN, Akay EM, Evangelou N.
Lymphomatoid papulosis: a cutaneous lymphoproliferative
disorder in a patient on fingolimod for multiple sclerosis.
Multiple Sclerosis Journal. 2016 Jan;22(1):122-4.
- Tyler KL. Fingolimod and risk of varicella-zoster virus
infection: back to the future with an old infection and a
new drug. JAMA neurology. 2015 Jan 1;72(1):10-3.
- Pfender N, Jelcic I, Linnebank M, Schwarz U, Martin
R. Reactivation of herpesvirus under fingolimod: a case of
severe herpes simplex encephalitis. Neurology. 2015 Jun
- Achtnichts L, Obreja O, Conen A, Fux CA, Nedeltchev
K. Cryptococcal meningoencephalitis in a patient
with multiple sclerosis treated with fingolimod. Jama
Neurology. 2015 Oct 1;72(10):1203-5.
- Huang D. Disseminated cryptococcosis in a patient
with multiple sclerosis treated with fingolimod. Neurology.
2015 Sep 15;85(11):1001-3.
- Yuen HL, Brown S, Chan N, Grigoriadis G. Immune
thrombocytopenic purpura associated with fingolimod.
Case Reports. 2017 Sep 8;2017.
- Kappos L, Radue EW, O’Connor P, Polman C,
Hohlfeld R, Calabresi P, et al. A placebo-controlled trial
of oral fingolimod in relapsing multiple sclerosis. New
England Journal of Medicine. 2010 Feb 4;362(5):387-401.
- Confavreux C, O’Connor P, Comi G, Freedman MS, Miller AE, Olsson TP, et al. Oral teriflunomide for patients
with relapsing multiple sclerosis (TOWER): a randomised,
double-blind, placebo-controlled, phase 3 trial. The Lancet
Neurology. 2014 Mar 1;13(3):247-56.
- O’Connor P, Comi G, Freedman MS, Miller AE,
Kappos L, Bouchard JP, et al. Long-term safety and efficacy
of teriflunomide: nine-year follow-up of the randomized
TEMSO study. Neurology. 2016 Mar 8;86(10):920-30.
- O’Connor P, Wolinsky JS, Confavreux C, Comi G,
Kappos L, Olsson TP, et al. Randomized trial of oral
teriflunomide for relapsing multiple sclerosis. New
England Journal of Medicine. 2011 Oct 6;365(14):1293-
- O’connor PW, Li D, Freedman MS, Bar-Or A, Rice
GP, Confavreux C, et al. A Phase II study of the safety
and efficacy of teriflunomide in multiple sclerosis with
relapses. Neurology. 2006 Mar 28;66(6):894-900.
- Europa, E. Aubagio. 2013 [cited 2013 27 June
2013]; Available from: https://www.ema.europa.eu/en/
- Gerschenfeld G, Servy A, Valeyrie-Allanore L, de
Prost N, Cecchini J. Fatal toxic epidermal necrolysis in a
patient on teriflunomide treatment for relapsing multiple
sclerosis. Multiple Sclerosis Journal. 2015 Oct;21(11):1476-
- Dereure O, Camu W. Teriflunomide-induced
psoriasiform changes of fingernails: a new example
of paradoxical side effect?. International Journal of
Dermatology. 2017 Sep 7;56(12):1479-81.
- Mancinelli L, Amerio P, di Ioia M, Di Tommaso V, De
Luca G, Onofrj M, Lugaresi A. Nail loss after teriflunomide
treatment: A new potential adverse event. Multiple
Sclerosis and Related Disorders. 2017 Nov 1;18: 170-2.
- Negrotto L, Correale J. Palmar pustular psoriasis
associated with teriflunomide treatment. Multiple sclerosis
and related disorders. 2019 Jan 1;27: 400-2.
- Schweckendiek W. Treatment of psoriasis vulgaris.
Medizinische Monatsschrift. 1959 Feb;13(2):103.
- Gold R, Linker RA, Stangel M. Fumaric acid and its
esters: an emerging treatment for multiple sclerosis with
antioxidative mechanism of action. Clinical Immunology.
2012 Jan 1;142(1):44-8.
- Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni
G, Selmaj K, et al. Placebo-controlled phase 3 study of
oral BG-12 for relapsing multiple sclerosis. New England
Journal of Medicine. 2012 Sep 20;367(12):1098-107.
- Fox RJ, Miller DH, Phillips JT, Hutchinson M,
Havrdova E, Kita M, et al. Placebo-controlled phase 3
study of oral BG-12 or glatiramer in multiple sclerosis. New
England Journal of Medicine. 2012 Sep 20;367(12):1087-
- Zadeh AR, Ghadimi K, Ataei A, Askari M, Sheikhinia
N, Tavoosi N, et al. Mechanism and adverse effects
of multiple sclerosis drugs: a review article. Part 2.
International Journal of Physiology, Pathophysiology and
Pharmacology. 2019; 11(4):105-114.
- Bernardini LR, Zecca C, Clerici VT, Gobbi C, Mantegazza
R, Rossi S. Severe articular and musculoskeletal pain: an
unexpected side effect of dimethyl-fumarate therapy for
multiple sclerosis. Journal of the neurological sciences.
2016 Oct 15; 369:139-40.
- Losavio FA, Lucchini M, De Fino C, Mirabella M, Nociti
V. Transient hair loss during treatment with dimethylfumarate
for multiple sclerosis. Multiple Sclerosis and Related Disorders. 2016 May 1;7: 68-9.
- Mrowietz U, Barker J, Boehncke WH, Iversen L,
Kirby B, Naldi L, et al. Clinical use of dimethyl fumarate
in moderate-to-severe plaque-type psoriasis: a European
expert consensus. Journal of the European Academy of
Dermatology and Venereology. 2018 Oct; 32:3-14.
- Bilgic-Temel A, Das S, Murrell DF. Successful
management of bullous pemphigoid with dimethyl
fumarate therapy: A case report. International Journal of
Women’s Dermatology. 2019 Jul 1;5(3):179-80.
- Miyamoto D, Santi CG, Aoki V, Maruta CW. Bullous
pemphigoid. Anais Brasileiros de Dermatologia. 2019
- Stavropoulos PG, Soura E, Antoniou C. Drug-induced
pemphigoid: a review of the literature. Journal of the
European Academy of Dermatology and Venereology.