Rumień wielopostaciowy – Etiologia i przyczyny

Rumień wielopostaciowy
Etiologia i przyczyny

Rumień wielopostaciowy (erythema multiforme, EM) jest ostrą, immunologiczną reakcją nadwrażliwości typu IV, charakteryzującą się tarczowatymi wykwitami skórnymi i zmianami śluzówkowymi, najczęściej na kończynach. Etiologia jest wieloczynnikowa, z dominującą rolą infekcji, które odpowiadają za około 90% przypadków. Najczęstszym patogenem jest wirus Herpes simplex (HSV), odpowiedzialny za 50-70% EM, głównie HSV-1, z mechanizmem patogenezy opartym na transportowaniu fragmentów DNA wirusa do naskórka przez komórki CD34+ i indukcji odpowiedzi immunologicznej z udziałem IFN-γ. Drugą istotną przyczyną jest zakażenie Mycoplasma pneumoniae, szczególnie w EM typu major u dzieci. Inne czynniki infekcyjne obejmują wirusy CMV, EBV, HAV, HBV, HCV, VZV, SARS-CoV-2 oraz bakterie i grzyby. Reakcje polekowe stanowią około 10% EM minor i 50% EM major, z mechanizmem opartym na apoptozie keratynocytów indukowanej przez TNF-α, a najczęściej wywołującymi lekami są sulfonamidy (30% przypadków), penicyliny, NLPZ, leki przeciwdrgawkowe i inne. Szczepionki oraz choroby współistniejące (autoimmunologiczne, nowotworowe) również mogą wywoływać EM.

Etiologia rumienia wielopostaciowego

Infekcje jako główna przyczyna
Leki jako przyczyna EM
Szczepionki
Choroby współistniejące
Czynniki fizyczne i inne
Idiopatyczny rumień wielopostaciowy

Genetyczne predyspozycje
Mechanizm patogenetyczny

Mechanizm EM związanego z HSV
Mechanizm EM polekowego

Nawracający i przetrwały rumień wielopostaciowy
Czynniki ryzyka
Etiologia rumienia wielopostaciowego – podsumowanie

Kolejne rozdziały

Etiologia rumienia wielopostaciowego

Rumień wielopostaciowy (erythema multiforme, EM) jest ostrą, immunologicznie mediowaną reakcją nadwrażliwości, która manifestuje się charakterystycznymi zmianami skórnymi i śluzówkowymi w postaci tarczowatych wykwitów, najczęściej zlokalizowanych na kończynach¹². Etiologia tego schorzenia jest złożona i wieloczynnikowa. Rumień wielopostaciowy może być wywołany przez różne czynniki, a mechanizm jego powstawania opiera się na reakcji nadwrażliwości typu IV, w której uczestniczą zarówno komórki T CD4+ pomocnicze, jak i CD8+ cytotoksyczne³⁴.

Infekcje jako główna przyczyna

Infekcje są zdecydowanie najczęstszą przyczyną rumienia wielopostaciowego, odpowiadając za około 90% wszystkich przypadków⁵⁶. Wśród czynników infekcyjnych dominują:

Wirusy Herpes simplex

Zakażenie wirusem Herpes simplex (HSV) jest najczęstszą przyczyną EM, odpowiedzialną za 50-70% wszystkich przypadków⁷⁸. HSV typu 1 (HSV-1) jest częstszym czynnikiem etiologicznym niż HSV-2, choć obydwa typy mogą wywoływać to schorzenie⁹¹⁰. Rumień wielopostaciowy wywołany przez HSV określany jest jako herpes-associated erythema multiforme (HAEM)¹¹.

Co istotne, DNA wirusa HSV jest wykrywane u prawie połowy pacjentów z idiopatycznym EM, co sugeruje, że rzeczywista częstość występowania EM związanego z HSV jest nawet wyższa niż się powszechnie uważa¹². Warto podkreślić, że EM może wystąpić nawet bez aktywnych zmian opryszczkowych, co oznacza, że infekcja HSV może być subkliniczna¹³¹⁴.

Mechanizm patogenezy EM związanego z HSV jest dobrze poznany. Fragmenty DNA wirusa HSV są transportowane do naskórka przez komórki CD34+, gdzie komórki T gromadzą się w odpowiedzi na antygeny HSV i uszkodzone komórki¹⁵. W zmianach skórnych charakterystycznych dla HAEM stwierdza się obecność interferonu gamma (IFN-γ)¹⁶¹⁷.

Mycoplasma pneumoniae

Drugą najczęstszą przyczyną infekcyjną EM, szczególnie u dzieci, jest zakażenie bakterią Mycoplasma pneumoniae¹⁸¹⁹. Jest to najczęstsza przyczyna rumienia wielopostaciowego typu major²⁰. Bakteria ta jest odpowiedzialna za rozwój atypowego zapalenia płuc, które może poprzedzać wystąpienie zmian skórnych²¹.

Inne czynniki infekcyjne

Oprócz HSV i Mycoplasma pneumoniae, EM może być wywołany przez szereg innych patogenów²²:

Inne wirusy: cytomegalowirus (CMV), wirus Epsteina-Barr (EBV), wirusy zapalenia wątroby (HAV, HBV, HCV), wirus ospy wietrznej i półpaśca (VZV), adenowirusy, wirus grypy, wirus SARS-CoV-2, parwowirus B19, orf²³²⁴
Bakterie: paciorkowce hemolizujące, Borelia, Neisseria meningitidis, Pseudomonas, Salmonella, Staphylococcus, Yersinia, Treponema pallidum²⁵
Grzyby: kandydoza sromu i pochwy, histoplazmoza²⁶²⁷

Leki jako przyczyna EM

Reakcje polekowe są drugą najczęstszą przyczyną rumienia wielopostaciowego, odpowiadając za około 10% przypadków EM minor, ale aż 50% przypadków EM major²⁸²⁹. W przeciwieństwie do EM wywołanego przez HSV, w zmianach polekowych stwierdza się obecność czynnika martwicy nowotworów alfa (TNF-α), a nie interferonu gamma³⁰³¹.

Mechanizm uszkodzenia w EM wywołanym przez leki różni się od mechanizmu w EM wywołanym przez wirusy. W EM polekowym reaktywne metabolity konkretnego leku indukują chorobę, a apoptoza keratynocytów jest wywołana przez TNF-α uwalniany z keratynocytów, makrofagów i monocytów, co prowadzi do uszkodzenia tkanki³².

Do leków najczęściej wywołujących rumień wielopostaciowy należą³³³⁴:

Antybiotyki: sulfonamidy (najczęstsza przyczyna, stanowiąca około 30% przypadków), penicyliny, cefalosporyny, makrolidy, tetracykliny, nitrofurantoina³⁵³⁶
Niesteroidowe leki przeciwzapalne (NLPZ): ibuprofen, diklofenak, salicylany³⁷³⁸
Leki przeciwdrgawkowe: fenytoina, barbiturany, karbamazepina, lamotrygina³⁹⁴⁰
Inne: allopurynol, statyny, inhibitory TNF-α, leki przeciwgruźlicze, leki hormonalne (estrogeny, progesteron), leki przeciwmalaryczne⁴¹

Warto zaznaczyć, że ryzyko rozwoju EM major po zastosowaniu trimetoprimu-sulfametoksazolu (Bactrim) jest nawet 40 razy wyższe u osób zakażonych HIV⁴².

Szczepionki

Szczepionki są rzadszą, ale udokumentowaną przyczyną rumienia wielopostaciowego, szczególnie u niemowląt⁴³⁴⁴. Do szczepionek związanych z EM należą⁴⁵⁴⁶:

Szczepionka przeciwko odrze, śwince i różyczce (MMR)
Szczepionka przeciwko ospie prawdziwej
Szczepionka przeciwko wirusowemu zapaleniu wątroby typu B
Szczepionka przeciwko błonicy, tężcowi i krztuścowi (Tdap)
Szczepionka przeciwko grypie
Szczepionka przeciwko meningokokom
Szczepionka przeciwko pneumokokom
Szczepionka BCG (Bacille Calmette-Guérin)

Choroby współistniejące

Rumień wielopostaciowy może być również związany z różnymi chorobami współistniejącymi⁴⁷⁴⁸:

Choroby autoimmunologiczne: toczeń rumieniowaty układowy (SLE), zespół Rowella, choroby zapalne jelit (choroba Leśniowskiego-Crohna, wrzodziejące zapalenie jelita grubego)⁴⁹⁵⁰
Nowotwory: białaczka, chłoniak, rak nerkowokomórkowy, gruczolakorak żołądka (często związane z przewlekłym i opornym na leczenie EM)⁵¹⁵²
Sarkoidoza⁵³

Czynniki fizyczne i inne

Do rzadszych przyczyn rumienia wielopostaciowego należą⁵⁴⁵⁵:

Czynniki fizyczne: promieniowanie słoneczne, zimno, radioterapia
Tatuaże
Konserwanty i aromaty w żywności (kwas benzoesowy, cynamon)
Czynniki hormonalne (menstruacja, ciąża)

Idiopatyczny rumień wielopostaciowy

Pomimo licznych zidentyfikowanych czynników etiologicznych, u 25-50% pacjentów z rumieniem wielopostaciowym nie udaje się ustalić konkretnej przyczyny⁵⁶⁵⁷. Przypadki te określa się jako idiopatyczny rumień wielopostaciowy⁵⁸.

Genetyczne predyspozycje

Istnieją dowody sugerujące genetyczną predyspozycję do rozwoju rumienia wielopostaciowego. Wykazano związek między EM a obecnością określonych antygenów zgodności tkankowej (HLA), w tym HLA B-15, HLA Aw33, HLA DRw53, HLA DQB-1 i HLA DQ3⁵⁹. Może to tłumaczyć, dlaczego tylko niektóre osoby z infekcją HSV rozwijają EM, podczas gdy u większości zakażonych osób takie powikłanie nie występuje⁶⁰.

Mechanizm patogenetyczny

Rumień wielopostaciowy jest wynikiem reakcji nadwrażliwości typu IV, w której uczestniczą limfocyty T⁶¹. Mechanizm powstawania EM różni się w zależności od czynnika wywołującego⁶²:

Mechanizm EM związanego z HSV

W przypadku EM wywołanego przez HSV, wirus jest fagocytowany przez komórki jednojądrzaste, które ekspresjonują antygen limfocytów skórnych (receptor kierujący do skóry). Pochłonięte wirusowe DNA jest następnie przenoszone do naskórka i do keratynocytów. W warstwie keratynocytów ekspresja fragmentów wirusowego DNA indukuje odpowiedź immunologiczną komórkową, w tym produkcję interferonu gamma, który nasila proces zapalny⁶³. W zmianach skórnych związanych z HSV wykrywa się 100% DNA dla wirusowej polimerazy DNA (genu Pol) w keratynocytach⁶⁴.

Mechanizm EM polekowego

W przeciwieństwie do EM wywołanego przez wirusy, mechanizm EM polekowego nie wydaje się być wynikiem opóźnionego typu nadwrażliwości. W tym przypadku reaktywne metabolity konkretnego leku indukują chorobę, a apoptoza keratynocytów jest wywołana przez czynnik martwicy nowotworów alfa (TNF-α) uwalniany z keratynocytów, makrofagów i monocytów, co prowadzi do uszkodzenia tkanki⁶⁵⁶⁶.

Nawracający i przetrwały rumień wielopostaciowy

Rumień wielopostaciowy może występować jako pojedynczy epizod, ale u niektórych pacjentów ma charakter nawracający⁶⁷. Nawracający EM jest najczęściej związany z reaktywacją wirusa HSV-1 i HSV-2, choć infekcja może być klinicznie bezobjawowa⁶⁸⁶⁹.

Rzadszą postacią jest przetrwały EM, charakteryzujący się ciągłym pojawianiem się zmian skórnych i znaczną opornością na leczenie. Przypadki przetrwałego EM były wiązane z chorobami nowotworowymi, zapalnymi chorobami jelit oraz infekcjami wirusem Epsteina-Barr, cytomegalowirusem, wirusem zapalenia wątroby typu C i wirusem grypy⁷⁰.

Czynniki ryzyka

Do czynników zwiększających ryzyko wystąpienia rumienia wielopostaciowego należą⁷¹:

Płeć męska
Wcześniejsza historia EM
Zakażenie HIV (zwiększa ryzyko EM związanego z lekami)
Ciąża
Predyspozycje genetyczne

Rumień wielopostaciowy może występować w każdym wieku, ale najczęściej dotyka młodych dorosłych w wieku 20-40 lat⁷². U dzieci najczęściej występuje po 4 roku życia, z najwyższą częstością w wieku około 11-12 lat⁷³.

Etiologia rumienia wielopostaciowego – podsumowanie

Rumień wielopostaciowy jest złożonym schorzeniem o wieloczynnikowej etiologii. Główne przyczyny to:

Infekcje (90% przypadków), z dominującą rolą wirusa Herpes simplex (50-70% przypadków)
Reakcje polekowe (10% przypadków EM minor, 50% przypadków EM major)
Szczepionki (rzadko, głównie u niemowląt)
Choroby współistniejące (autoimmunologiczne, nowotworowe)
Czynniki fizyczne i inne

Zrozumienie etiologii rumienia wielopostaciowego ma kluczowe znaczenie dla właściwego postępowania terapeutycznego, które powinno obejmować leczenie choroby podstawowej, jeśli jest ona znana⁷⁴. W przypadku EM wywołanego przez HSV, profilaktyczne stosowanie acyklowiru może zapobiegać nawrotom⁷⁵, podczas gdy w przypadku EM wywołanego przez leki kluczowe jest odstawienie podejrzanego preparatu⁷⁶⁷⁷.

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Materiały źródłowe

#1 Erythema Multiforme – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470259/
Erythema multiforme is an immune-mediated hypersensitivity reaction affecting both the skin and mucous membranes, characterized by the appearance of macular, papular, or bullous lesions that often form distinct „target lesions,” primarily found on the extremities. […] Erythema multiforme is most often triggered by infections, particularly herpes simplex virus, but can also be caused by medications, autoimmune disorders, and occasionally vaccines. […] Erythema multiforme’s etiologies are variable and numerous, and its clinical course is generally favorable. […] The etiology of erythema multiforme is multifactorial, including infections, medications, autoimmune disease, malignancy, immunizations, radiation exposure, allergic contact dermatitis, sarcoidosis, and menstruation. […] Approximately 90% of cases of erythema multiforme are caused by infections (viral, bacterial, or fungal), with herpes simplex virus being the most common culprit.
#2 Erythema multiforme – Wikipedia
https://en.wikipedia.org/wiki/Erythema_multiforme
Erythema multiforme (EM) is an immune-mediated inflammatory skin condition associated with several viral infections, that appears with red patches evolving into target lesions, typically on both hands. It is typically associated with infection by either herpes simplex virus or Mycoplasma pneumoniae. […] Erythema multiforme typically arises as a type IV hypersensitivity reaction to certain infections or, rarely, certain medications. The most common trigger is an infection with any type of the herpes simplex virus. The second most common trigger, and the most common in children, is infection with Mycoplasma pneumoniae, most commonly as an atypical pneumonia. […] The pathogenic immune response in EM involves both CD4+ helper T cells and CD8+ cytotoxic T cells, which orchestrate a type IV hypersensitivity reaction.
#3 Erythema multiforme – Wikipedia
https://en.wikipedia.org/wiki/Erythema_multiforme
Erythema multiforme (EM) is an immune-mediated inflammatory skin condition associated with several viral infections, that appears with red patches evolving into target lesions, typically on both hands. It is typically associated with infection by either herpes simplex virus or Mycoplasma pneumoniae. […] Erythema multiforme typically arises as a type IV hypersensitivity reaction to certain infections or, rarely, certain medications. The most common trigger is an infection with any type of the herpes simplex virus. The second most common trigger, and the most common in children, is infection with Mycoplasma pneumoniae, most commonly as an atypical pneumonia. […] The pathogenic immune response in EM involves both CD4+ helper T cells and CD8+ cytotoxic T cells, which orchestrate a type IV hypersensitivity reaction.
#4 Erythema multiforme: a case series and review of literature – MedCrave online
https://medcraveonline.com/OAJTMR/erythema-multiforme-a-case-series-and-review-of-literature.html
Drug-associated EM is reported in less than 10% of cases and common medications that induce EM are nonsteroidal anti-inflammatory drugs such as diclofenac, ibuprofen, and salicylates, sulfa drugs -sulfonamides, co-trimoxazole, anti-consultants such as phenytoin and carbamazepine. […] EM seems to be a T- cell-mediated immune reaction to precipitating stimuli, leading to a cytotoxic immunological attack on non-self-antigen expressing keratinocytes followed by sub-epithelial and intra-epithelial vesicle formation, eventually leading to widespread blistering and erosion. […] In HSV associated EM, HSV-DNA fragments in the skin or mucosa trigger the disease. Virus fragments get transported to the epithelium by CD34+ cells, and T cells accumulate in response to HSV antigens and damaged cells.
#5 Erythema Multiforme – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470259/
Erythema multiforme is an immune-mediated hypersensitivity reaction affecting both the skin and mucous membranes, characterized by the appearance of macular, papular, or bullous lesions that often form distinct „target lesions,” primarily found on the extremities. […] Erythema multiforme is most often triggered by infections, particularly herpes simplex virus, but can also be caused by medications, autoimmune disorders, and occasionally vaccines. […] Erythema multiforme’s etiologies are variable and numerous, and its clinical course is generally favorable. […] The etiology of erythema multiforme is multifactorial, including infections, medications, autoimmune disease, malignancy, immunizations, radiation exposure, allergic contact dermatitis, sarcoidosis, and menstruation. […] Approximately 90% of cases of erythema multiforme are caused by infections (viral, bacterial, or fungal), with herpes simplex virus being the most common culprit.
#6 Erythema Multiforme
https://fpnotebook.com/ENT/Derm/ErythmMltfrm.htm
Erythema Multiforme Major (Stevens Johnson Syndrome) […] Infections (90% of cases) […] Herpes Simplex Virus and Mycoplasma pneumoniae are most common […] Medications (10% of cases)
#7 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme […] However, up to 90% of Erythema Multiforme Minor cases are thought due to infections […] Herpes Simplex Virus (50%) […] HSV may be cause even without active lesions […] Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme […] Mycoplasma pneumoniae […] Second most common cause (esp. children) […] Most common cause of erythema mutiforme major […] Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma) […] Medications cause 50% of Stevens Johnson […] Medications cause 90% of Toxic Epidermal Necrolysis […] Most common with NSAIDS, antiepileptics and Antibiotics […] Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
#8 Erythema multiforme – Wikipedia
https://en.wikipedia.org/wiki/Erythema_multiforme
Rarely, some patients may suffer from a persistent and treatment-resistant form of erythema multiforme caused by the Epstein-Barr virus. […] Herpes simplex virus (HSV) is by far the most frequent cause of erythema multiforme. HSV DNA is also detected in nearly half of patients with idiopathic EM, suggesting that the true frequency is even higher than traditionally thought. […] 100% of HSV-associated EM cases are found to have DNA for viral-type DNA polymerase (Pol) gene within keratinocytes. Despite this association, an active and infectious form of HSV has never been found in a patient suffering from EM, indicating that it is exclusively a post-viral hypersensitivity syndrome in these patients, rather than a symptom of the virus itself.
#9 Erythema Multiforme – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470259/
Moreover, a strong association between the COVID-19 vaccine and erythema multiforme has recently been found. […] Autoimmune conditions (eg, systemic lupus erythematosus) are also associated with erythema multiforme, particularly causing a typical but rare syndrome called Rowell syndrome. […] Another common cause of erythema multiforme, particularly in children, is Mycoplasma pneumoniae infection. […] Although herpes simplex virus (HSV) types 1 and 2 and Mycoplasma pneumonia are the common causes of erythema multiforme, many other viral, fungal, and bacterial infections have been implicated. […] Human immunodeficiency virus (HIV) infection and HIV treatment medications have been found to have a direct or indirect effect on the development of erythema multiforme. […] Also, various vaccines leading to erythema multiforme have been reported, including Bacille Calmette-Gurin, oral polio, vaccinia, and tetanus/diphtheria vaccines. […] Drugs associated with erythema multiforme include antibiotics (eg, penicillins, cephalosporins, macrolides, and sulfonamides), antituberculosis agents, and antipyretics.
#10 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme […] However, up to 90% of Erythema Multiforme Minor cases are thought due to infections […] Herpes Simplex Virus (50%) […] HSV may be cause even without active lesions […] Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme […] Mycoplasma pneumoniae […] Second most common cause (esp. children) […] Most common cause of erythema mutiforme major […] Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma) […] Medications cause 50% of Stevens Johnson […] Medications cause 90% of Toxic Epidermal Necrolysis […] Most common with NSAIDS, antiepileptics and Antibiotics […] Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
#11 What Does Erythema Multiforme Look Like?
https://www.icliniq.com/articles/skin-care/erythema-multiforme
Erythema multiforme is a skin condition that may be caused by an infection or an adverse response to medication. […] Herpes simplex virus (HSV) infection is the most common cause of erythema multiforme; other potential triggers include various infections, drugs, and immunizations. […] The primary causes of erythema multiforme include herpes simplex virus (HSV) type 1 and 2 infections. The other causes may include the following: Antibiotics include Penicillins, cephalosporins, macrolides, sulfonamides, anti-tuberculosis agents, and antipyretics. […] The herpes simplex virus typically brings on this disorder. It has also been linked to fungus infections and Mycoplasma pneumonia. These additional factors might be to blame, a reaction to a particular drug. […] HAEM (herpes simplex virus-associated erythema multiforme) is a viral disease with an autoimmune component caused by the herpes simplex virus (HSV). It is considered to be a hypersensitive reaction associated with certain medications and infections.
#12 Erythema multiforme – Wikipedia
https://en.wikipedia.org/wiki/Erythema_multiforme
Rarely, some patients may suffer from a persistent and treatment-resistant form of erythema multiforme caused by the Epstein-Barr virus. […] Herpes simplex virus (HSV) is by far the most frequent cause of erythema multiforme. HSV DNA is also detected in nearly half of patients with idiopathic EM, suggesting that the true frequency is even higher than traditionally thought. […] 100% of HSV-associated EM cases are found to have DNA for viral-type DNA polymerase (Pol) gene within keratinocytes. Despite this association, an active and infectious form of HSV has never been found in a patient suffering from EM, indicating that it is exclusively a post-viral hypersensitivity syndrome in these patients, rather than a symptom of the virus itself.
#13 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme […] However, up to 90% of Erythema Multiforme Minor cases are thought due to infections […] Herpes Simplex Virus (50%) […] HSV may be cause even without active lesions […] Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme […] Mycoplasma pneumoniae […] Second most common cause (esp. children) […] Most common cause of erythema mutiforme major […] Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma) […] Medications cause 50% of Stevens Johnson […] Medications cause 90% of Toxic Epidermal Necrolysis […] Most common with NSAIDS, antiepileptics and Antibiotics […] Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
#14 Erythema Multiforme | AAFP
https://www.aafp.org/pubs/afp/issues/2006/1201/p1883.html
Erythema multiforme is a skin condition considered to be a hypersensitivity reaction to infections or drugs. […] Erythema multiforme usually occurs in adults 20 to 40 years of age, although it can occur in patients of all ages. Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50 percent of cases. Mycoplasma pneumoniae is another commonly reported etiology, especially in children, as is fungal infection. The medications most often associated with erythema multiforme are barbiturates, hydantoins, nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, and sulfonamides. […] Recurrent erythema multiforme often is secondary to HSV-1 and -2 reactivation, although the HSV may be clinically silent. […] The pathogenesis of herpes-associated erythema multiforme has been well studied and is consistent with a delayed-type hypersensitivity reaction. […] Drug-associated erythema multiforme lesions test positive for tumor necrosis factor and not interferon- as in herpes-associated erythema multiforme lesions, suggesting a varying mechanism.
#15 Erythema multiforme: a case series and review of literature – MedCrave online
https://medcraveonline.com/OAJTMR/erythema-multiforme-a-case-series-and-review-of-literature.html
Drug-associated EM is reported in less than 10% of cases and common medications that induce EM are nonsteroidal anti-inflammatory drugs such as diclofenac, ibuprofen, and salicylates, sulfa drugs -sulfonamides, co-trimoxazole, anti-consultants such as phenytoin and carbamazepine. […] EM seems to be a T- cell-mediated immune reaction to precipitating stimuli, leading to a cytotoxic immunological attack on non-self-antigen expressing keratinocytes followed by sub-epithelial and intra-epithelial vesicle formation, eventually leading to widespread blistering and erosion. […] In HSV associated EM, HSV-DNA fragments in the skin or mucosa trigger the disease. Virus fragments get transported to the epithelium by CD34+ cells, and T cells accumulate in response to HSV antigens and damaged cells.
#16 Erythema Multiforme | AAFP
https://www.aafp.org/pubs/afp/issues/2006/1201/p1883.html
Erythema multiforme is a skin condition considered to be a hypersensitivity reaction to infections or drugs. […] Erythema multiforme usually occurs in adults 20 to 40 years of age, although it can occur in patients of all ages. Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50 percent of cases. Mycoplasma pneumoniae is another commonly reported etiology, especially in children, as is fungal infection. The medications most often associated with erythema multiforme are barbiturates, hydantoins, nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, and sulfonamides. […] Recurrent erythema multiforme often is secondary to HSV-1 and -2 reactivation, although the HSV may be clinically silent. […] The pathogenesis of herpes-associated erythema multiforme has been well studied and is consistent with a delayed-type hypersensitivity reaction. […] Drug-associated erythema multiforme lesions test positive for tumor necrosis factor and not interferon- as in herpes-associated erythema multiforme lesions, suggesting a varying mechanism.
#17
https://www.jpad.com.pk/index.php/jpad/article/view/2403
Erythema multiforme is a common reactive skin disease to different endogenous and exogenous triggers with characteristic clinical features of variable severity. […] Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. […] Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions.
#18 Erythema Multiforme – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470259/
Moreover, a strong association between the COVID-19 vaccine and erythema multiforme has recently been found. […] Autoimmune conditions (eg, systemic lupus erythematosus) are also associated with erythema multiforme, particularly causing a typical but rare syndrome called Rowell syndrome. […] Another common cause of erythema multiforme, particularly in children, is Mycoplasma pneumoniae infection. […] Although herpes simplex virus (HSV) types 1 and 2 and Mycoplasma pneumonia are the common causes of erythema multiforme, many other viral, fungal, and bacterial infections have been implicated. […] Human immunodeficiency virus (HIV) infection and HIV treatment medications have been found to have a direct or indirect effect on the development of erythema multiforme. […] Also, various vaccines leading to erythema multiforme have been reported, including Bacille Calmette-Gurin, oral polio, vaccinia, and tetanus/diphtheria vaccines. […] Drugs associated with erythema multiforme include antibiotics (eg, penicillins, cephalosporins, macrolides, and sulfonamides), antituberculosis agents, and antipyretics.
#19 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme […] However, up to 90% of Erythema Multiforme Minor cases are thought due to infections […] Herpes Simplex Virus (50%) […] HSV may be cause even without active lesions […] Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme […] Mycoplasma pneumoniae […] Second most common cause (esp. children) […] Most common cause of erythema mutiforme major […] Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma) […] Medications cause 50% of Stevens Johnson […] Medications cause 90% of Toxic Epidermal Necrolysis […] Most common with NSAIDS, antiepileptics and Antibiotics […] Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
#20 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme […] However, up to 90% of Erythema Multiforme Minor cases are thought due to infections […] Herpes Simplex Virus (50%) […] HSV may be cause even without active lesions […] Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme […] Mycoplasma pneumoniae […] Second most common cause (esp. children) […] Most common cause of erythema mutiforme major […] Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma) […] Medications cause 50% of Stevens Johnson […] Medications cause 90% of Toxic Epidermal Necrolysis […] Most common with NSAIDS, antiepileptics and Antibiotics […] Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
#21 Erythema Multiforme – UF Health
https://ufhealth.org/conditions-and-treatments/erythema-multiforme
Erythema multiforme (EM) is an acute skin reaction that comes from an infection or another trigger. EM is a type of allergic reaction. In most cases, it occurs in response to an infection. In rare cases, it is caused by certain medicines or body-wide (systemic) illness. […] Infections that may lead to EM include: Viruses, such as herpes simplex that cause cold sores and genital herpes (most common). Bacteria, such as Mycoplasma pneumoniae that cause lung infection. Fungi, such as Histoplasma capsulatum, that cause histoplasmosis. […] Medicines that may cause EM include: NSAIDs, Allopurinol (treats gout), Certain antibiotics, such as sulfonamides and aminopenicillins, Anti-seizure medicines. […] Systemic illnesses that are associated with EM include: Inflammatory bowel disease, such as Crohn disease, Systemic lupus erythematosus.
#22 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
EM minor is regarded as being commonly triggered by HSV types 1 and 2, and HSV is the most common cause in young adults; in fact, many instances of idiopathic EM minor may be precipitated by subclinical HSV infection. […] Bacterial infections that may trigger EM include the following: Borreliosis, Catscratch disease, Diphtheria, Hemolytic streptococci, Legionellosis, Leprosy, Neisseria meningitidis, Mycobacterium avium complex, Mycoplasma pneumoniae, Pneumococci, Tuberculosis, Proteus/Pseudomonas/Salmonella/Staphylococcus/Yersinia species, Treponema pallidum, Tularemia, Vibrio parahaemolyticus, Vincent disease, Rickettsial infections. […] Viral infections that may trigger EM include the following: Adenovirus, Coxsackievirus B5, Cytomegalovirus (CMV), Echovirus, Enterovirus, EBV, Hepatitis A/B/C viruses (HAV/HBV/HCV), HSV, Influenza, Measles, Mumps, Paravaccinia, Parvovirus B19, Poliomyelitis, Varicella-zoster virus (VZV), Variola.
#23 Erythema multiforme – DermNet
https://dermnetnz.org/topics/erythema-multiforme
Erythema multiforme is precipitated by herpes simplex virus (HSV) infection; alternative triggers include other infections, medications, and vaccinations. […] Infection precipitates 90% of cases, with HSV type 1 being the predominant cause. Other infectious triggers include: HSV type 2, Cytomegalovirus, Epstein-Barr virus, Influenza virus, Vulvovaginal candidiasis, SARS-CoV-2, Orf. […] Medications which may trigger erythema multiforme include: Antibiotics (including erythromycin, nitrofurantoin, penicillins, sulfonamides, and tetracyclines), Anti-epileptics, Non-steroidal anti-inflammatory drugs, Vaccinations (most common cause in infants). […] Other conditions associated with erythema multiforme (usually in persistent disease) include: Inflammatory bowel disease, Hepatitis C, Leukaemia, Lymphoma, Solid organ cancer malignancy.
#24 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
EM minor is regarded as being commonly triggered by HSV types 1 and 2, and HSV is the most common cause in young adults; in fact, many instances of idiopathic EM minor may be precipitated by subclinical HSV infection. […] Bacterial infections that may trigger EM include the following: Borreliosis, Catscratch disease, Diphtheria, Hemolytic streptococci, Legionellosis, Leprosy, Neisseria meningitidis, Mycobacterium avium complex, Mycoplasma pneumoniae, Pneumococci, Tuberculosis, Proteus/Pseudomonas/Salmonella/Staphylococcus/Yersinia species, Treponema pallidum, Tularemia, Vibrio parahaemolyticus, Vincent disease, Rickettsial infections. […] Viral infections that may trigger EM include the following: Adenovirus, Coxsackievirus B5, Cytomegalovirus (CMV), Echovirus, Enterovirus, EBV, Hepatitis A/B/C viruses (HAV/HBV/HCV), HSV, Influenza, Measles, Mumps, Paravaccinia, Parvovirus B19, Poliomyelitis, Varicella-zoster virus (VZV), Variola.
#25 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
EM minor is regarded as being commonly triggered by HSV types 1 and 2, and HSV is the most common cause in young adults; in fact, many instances of idiopathic EM minor may be precipitated by subclinical HSV infection. […] Bacterial infections that may trigger EM include the following: Borreliosis, Catscratch disease, Diphtheria, Hemolytic streptococci, Legionellosis, Leprosy, Neisseria meningitidis, Mycobacterium avium complex, Mycoplasma pneumoniae, Pneumococci, Tuberculosis, Proteus/Pseudomonas/Salmonella/Staphylococcus/Yersinia species, Treponema pallidum, Tularemia, Vibrio parahaemolyticus, Vincent disease, Rickettsial infections. […] Viral infections that may trigger EM include the following: Adenovirus, Coxsackievirus B5, Cytomegalovirus (CMV), Echovirus, Enterovirus, EBV, Hepatitis A/B/C viruses (HAV/HBV/HCV), HSV, Influenza, Measles, Mumps, Paravaccinia, Parvovirus B19, Poliomyelitis, Varicella-zoster virus (VZV), Variola.
#26 Erythema multiforme Information | Mount Sinai – New York
https://www.mountsinai.org/health-library/diseases-conditions/erythema-multiforme
Erythema multiforme (EM) is an acute skin reaction that comes from an infection or another trigger. EM is a self-limiting condition. This means it usually resolves on its own without treatment. […] EM is a type of allergic reaction. In most cases, it occurs in response to an infection. In rare cases, it is caused by certain medicines or body-wide (systemic) illness. […] Infections that may lead to EM include: Viruses, such as herpes simplex virus (HSV) that cause cold sores and genital herpes (most common). Bacteria, such as Mycoplasma pneumoniae that cause lung infection. Fungi, such as Histoplasma capsulatum, that cause histoplasmosis. […] Medicines that may cause EM include: Nonsteroidal anti-inflammatory drugs (NSAIDs). Allopurinol (treats gout). Certain antibiotics, such as sulfonamides and aminopenicillins. Anti-seizure medicines. […] Systemic illnesses that are associated with EM include: Inflammatory bowel disease, such as Crohn disease. Systemic lupus erythematosus (SLE).
#27 Erythema multiforme – DermNet
https://dermnetnz.org/topics/erythema-multiforme
Erythema multiforme is precipitated by herpes simplex virus (HSV) infection; alternative triggers include other infections, medications, and vaccinations. […] Infection precipitates 90% of cases, with HSV type 1 being the predominant cause. Other infectious triggers include: HSV type 2, Cytomegalovirus, Epstein-Barr virus, Influenza virus, Vulvovaginal candidiasis, SARS-CoV-2, Orf. […] Medications which may trigger erythema multiforme include: Antibiotics (including erythromycin, nitrofurantoin, penicillins, sulfonamides, and tetracyclines), Anti-epileptics, Non-steroidal anti-inflammatory drugs, Vaccinations (most common cause in infants). […] Other conditions associated with erythema multiforme (usually in persistent disease) include: Inflammatory bowel disease, Hepatitis C, Leukaemia, Lymphoma, Solid organ cancer malignancy.
#28 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
Erythema multiforme (EM) is an acute, self-limited, and sometimes recurring skin condition that is considered to be a type IV hypersensitivity reaction associated with certain infections, medications, and various other triggers. […] Precipitating factors include herpes simplex virus (HSV), Epstein-Barr virus (EBV), and histoplasmosis. […] More than 50% of all cases are attributed to medications. […] Many suspected etiologic factors have been reported to cause EM. Both EM and SJS may be induced by medications, but infectious agents are also considered to be a major cause of EM. […] Other reported risk factors include male sex and a previous history of EM; pregnancy may contribute to the development of EM as well. […] Infectious causes are more common in children and are implicated commonly in EM.
#29 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Erythema Multiforme Causes, Medication Causes of Erythema Mutiforme, Infectious Causes of Erythema Multiforme […] However, up to 90% of Erythema Multiforme Minor cases are thought due to infections […] Herpes Simplex Virus (50%) […] HSV may be cause even without active lesions […] Typically associated with HSV-1, but HSV-2 can also cause Erythema Multiforme […] Mycoplasma pneumoniae […] Second most common cause (esp. children) […] Most common cause of erythema mutiforme major […] Contrast with Erythema Multiforme Minor which is typically caused infections (esp. HSV, Mycoplasma) […] Medications cause 50% of Stevens Johnson […] Medications cause 90% of Toxic Epidermal Necrolysis […] Most common with NSAIDS, antiepileptics and Antibiotics […] Trimethoprim-Sulfamethoxazole (Bactrim) is the most common cause of Erythema Multiforme Major
#30 Erythema Multiforme: Recognition and Management | AAFP
https://www.aafp.org/pubs/afp/issues/2019/0715/p82.html
Erythema multiforme is caused by a cell-mediated immune response, and infections are associated with 90% of cases. Although herpes simplex virus (HSV) type 1 is the most commonly identified etiology, HSV-2 also has been shown to cause erythema multiforme. Mycoplasma pneumoniae is the second most common etiology, especially in children. Although medications cause less than 10% of erythema multiforme cases, many drugs have been associated with erythema multiforme, most commonly nonsteroidal anti-inflammatory drugs, antiepileptics, and antibiotics. Drug-associated lesions have tested positive for tumor necrosis factor- (TNF-), and HSV-associated lesions have tested positive for interferon. Types of antibiotics associated with erythema multiforme include sulfonamides, penicillins, erythromycin, nitrofurantoin, and tetracyclines. Other medications include barbiturates, phenothiazines, statins, and TNF- inhibitors.
#31
https://www.jpad.com.pk/index.php/jpad/article/view/2403
Erythema multiforme is a common reactive skin disease to different endogenous and exogenous triggers with characteristic clinical features of variable severity. […] Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. […] Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions.
#32 Erythema multiforme: a case series and review of literature – MedCrave online
https://medcraveonline.com/OAJTMR/erythema-multiforme-a-case-series-and-review-of-literature.html
Unlike virus-induced EM, mechanism of damage in drug-induced EM does not appear to be a result of the delayed type of hypersensitivity. In drug-induced EM, reactive metabolites of the particular drug induce the disease and keratinocyte apoptosis is induced by tumor necrosis factor alpha (TNF-) released from keratinocytes, macrophages, and monocytes leading to tissue damage.
#33 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
More than 50% of cases of EM major are related to medication use, but no test has conclusively established the link between a single case and a specific drug. […] The most common pharmacologic triggers are the sulfa drugs (30% of cases). […] Other agents that may cause EM include the following: Acarbose, Albendazole, Alendronate, Allopurinol, Arsenic, Bromofluorene, Quinine, Cimetidine, Clofibrate, Corticosteroids, Diclofenac, Didanosine, Dideoxycytidine, Dihydrocodeine phosphate, Diphosphonate, Estrogen, Etretinate, Fluconazole, Griseofulvin, Gabapentin, Granulocyte-macrophage colony-stimulating factor (GM-CSF), Hydralazine, Indapamide, Imiquimod, Indinavir, Lamotrigine, Methazolamide, Mefloquine, Methotrexate, Meprobamate, Mercurials, Minoxidil, Nifedipine, Nevirapine, Nivolumab, Nystatin, Nonsteroidal anti-inflammatory drugs (NSAIDs), Phenolphthalein, Piroxicam, Pyritinol, Progesterone, Potassium iodide, Secukinumab, Sulindac, Suramin, Saquinavir, Thiabendazole, Thiouracil, Terbinafine, Theophylline, Tramadol, Vandetanib, Verapamil.
#34 Erythema multiforme Information | Mount Sinai – New York
https://www.mountsinai.org/health-library/diseases-conditions/erythema-multiforme
Erythema multiforme (EM) is an acute skin reaction that comes from an infection or another trigger. EM is a self-limiting condition. This means it usually resolves on its own without treatment. […] EM is a type of allergic reaction. In most cases, it occurs in response to an infection. In rare cases, it is caused by certain medicines or body-wide (systemic) illness. […] Infections that may lead to EM include: Viruses, such as herpes simplex virus (HSV) that cause cold sores and genital herpes (most common). Bacteria, such as Mycoplasma pneumoniae that cause lung infection. Fungi, such as Histoplasma capsulatum, that cause histoplasmosis. […] Medicines that may cause EM include: Nonsteroidal anti-inflammatory drugs (NSAIDs). Allopurinol (treats gout). Certain antibiotics, such as sulfonamides and aminopenicillins. Anti-seizure medicines. […] Systemic illnesses that are associated with EM include: Inflammatory bowel disease, such as Crohn disease. Systemic lupus erythematosus (SLE).
#35 Erythema multiforme – DermNet
https://dermnetnz.org/topics/erythema-multiforme
Erythema multiforme is precipitated by herpes simplex virus (HSV) infection; alternative triggers include other infections, medications, and vaccinations. […] Infection precipitates 90% of cases, with HSV type 1 being the predominant cause. Other infectious triggers include: HSV type 2, Cytomegalovirus, Epstein-Barr virus, Influenza virus, Vulvovaginal candidiasis, SARS-CoV-2, Orf. […] Medications which may trigger erythema multiforme include: Antibiotics (including erythromycin, nitrofurantoin, penicillins, sulfonamides, and tetracyclines), Anti-epileptics, Non-steroidal anti-inflammatory drugs, Vaccinations (most common cause in infants). […] Other conditions associated with erythema multiforme (usually in persistent disease) include: Inflammatory bowel disease, Hepatitis C, Leukaemia, Lymphoma, Solid organ cancer malignancy.
#36 Erythema Multiforme: Recognition and Management | AAFP
https://www.aafp.org/pubs/afp/issues/2019/0715/p82.html
Erythema multiforme is caused by a cell-mediated immune response, and infections are associated with 90% of cases. Although herpes simplex virus (HSV) type 1 is the most commonly identified etiology, HSV-2 also has been shown to cause erythema multiforme. Mycoplasma pneumoniae is the second most common etiology, especially in children. Although medications cause less than 10% of erythema multiforme cases, many drugs have been associated with erythema multiforme, most commonly nonsteroidal anti-inflammatory drugs, antiepileptics, and antibiotics. Drug-associated lesions have tested positive for tumor necrosis factor- (TNF-), and HSV-associated lesions have tested positive for interferon. Types of antibiotics associated with erythema multiforme include sulfonamides, penicillins, erythromycin, nitrofurantoin, and tetracyclines. Other medications include barbiturates, phenothiazines, statins, and TNF- inhibitors.
#37 Erythema Multiforme: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/24475-erythema-multiforme
Erythema multiforme is your bodys reaction to an illness, infection or medicine. This condition affects your skin and causes a painful, itchy rash that looks like a bulls-eye or a target. […] Erythema multiforme is a skin reaction usually due to an infection or a medication. […] The exact cause of erythema multiforme is unknown, but studies show that erythema multiforme can be triggered by: An infection (mycoplasma pneumoniae or herpes simplex virus). A medication. […] A reaction to medication is a less common cause of erythema multiforme. Medications that trigger the condition vary for each person, but include: Antiseizure medications, Antibiotics, Nonsteroidal anti-inflammatory drugs (NSAIDs).
#38 Erythema multiforme
https://www.nhs.uk/conditions/erythema-multiforme/
Erythema multiforme is a skin condition that can be caused by an infection or some medicines. […] Erythema multiforme is usually caused by an infection, such as the herpes simplex virus (which also causes cold sores) or a bacteria that causes lung conditions like pneumonia. […] It can sometimes be caused by some vaccines or medicines such as non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, statins and medicines for epilepsy. […] If it’s caused by a medicine, you usually need to stop taking it. But do not stop taking any medicines without talking to a doctor first.
#39 Erythema Multiforme: Symptoms, Causes, Diagnosis, Treatment
https://www.verywellhealth.com/erythema-multiforme-7092731
Reactions to medications can also cause EM. The severe form of EM is often caused by medication rather than infection. […] Medication triggers for EM may include: Antibiotics (such as sulfonamides, tetracyclines, penicillins, amoxicillin, and ampicillin), Nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil/Motrin (ibuprofen), Anticonvulsants/antiepileptics (such as phenytoin and barbiturates), Some vaccines, Anesthesia, Allopurinol (used for gout). […] Some medical conditions associated with EM include: Inflammatory bowel disease (Crohn’s disease and ulcerative colitis), Systemic lupus erythematosus (lupus, an autoimmune disease), Hepatitis C (causes liver inflammation that can lead to liver damage), Leukemia (blood cancers), Lymphoma (cancers starting in the lymph system), Solid organ cancer malignancy.
#40 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
More than 50% of cases of EM major are related to medication use, but no test has conclusively established the link between a single case and a specific drug. […] The most common pharmacologic triggers are the sulfa drugs (30% of cases). […] Other agents that may cause EM include the following: Acarbose, Albendazole, Alendronate, Allopurinol, Arsenic, Bromofluorene, Quinine, Cimetidine, Clofibrate, Corticosteroids, Diclofenac, Didanosine, Dideoxycytidine, Dihydrocodeine phosphate, Diphosphonate, Estrogen, Etretinate, Fluconazole, Griseofulvin, Gabapentin, Granulocyte-macrophage colony-stimulating factor (GM-CSF), Hydralazine, Indapamide, Imiquimod, Indinavir, Lamotrigine, Methazolamide, Mefloquine, Methotrexate, Meprobamate, Mercurials, Minoxidil, Nifedipine, Nevirapine, Nivolumab, Nystatin, Nonsteroidal anti-inflammatory drugs (NSAIDs), Phenolphthalein, Piroxicam, Pyritinol, Progesterone, Potassium iodide, Secukinumab, Sulindac, Suramin, Saquinavir, Thiabendazole, Thiouracil, Terbinafine, Theophylline, Tramadol, Vandetanib, Verapamil.
#41 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
More than 50% of cases of EM major are related to medication use, but no test has conclusively established the link between a single case and a specific drug. […] The most common pharmacologic triggers are the sulfa drugs (30% of cases). […] Other agents that may cause EM include the following: Acarbose, Albendazole, Alendronate, Allopurinol, Arsenic, Bromofluorene, Quinine, Cimetidine, Clofibrate, Corticosteroids, Diclofenac, Didanosine, Dideoxycytidine, Dihydrocodeine phosphate, Diphosphonate, Estrogen, Etretinate, Fluconazole, Griseofulvin, Gabapentin, Granulocyte-macrophage colony-stimulating factor (GM-CSF), Hydralazine, Indapamide, Imiquimod, Indinavir, Lamotrigine, Methazolamide, Mefloquine, Methotrexate, Meprobamate, Mercurials, Minoxidil, Nifedipine, Nevirapine, Nivolumab, Nystatin, Nonsteroidal anti-inflammatory drugs (NSAIDs), Phenolphthalein, Piroxicam, Pyritinol, Progesterone, Potassium iodide, Secukinumab, Sulindac, Suramin, Saquinavir, Thiabendazole, Thiouracil, Terbinafine, Theophylline, Tramadol, Vandetanib, Verapamil.
#42 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Risk of Erythema Multiforme Major with Trimethoprim-Sulfamethoxazole is up to 40 fold higher in HIV […] Miscellaneous Medications […] Autoimmune Conditions […] Neoplasm […] Associated with Leukemia, Lymphoma […] Solid organ neoplasms (Renal Cell Carcinoma, Gastric Adenocarcinoma) may cause persistent and refractory cases […] May also be associated with Radiotherapy.
#43 Erythema multiforme – DermNet
https://dermnetnz.org/topics/erythema-multiforme
Erythema multiforme is precipitated by herpes simplex virus (HSV) infection; alternative triggers include other infections, medications, and vaccinations. […] Infection precipitates 90% of cases, with HSV type 1 being the predominant cause. Other infectious triggers include: HSV type 2, Cytomegalovirus, Epstein-Barr virus, Influenza virus, Vulvovaginal candidiasis, SARS-CoV-2, Orf. […] Medications which may trigger erythema multiforme include: Antibiotics (including erythromycin, nitrofurantoin, penicillins, sulfonamides, and tetracyclines), Anti-epileptics, Non-steroidal anti-inflammatory drugs, Vaccinations (most common cause in infants). […] Other conditions associated with erythema multiforme (usually in persistent disease) include: Inflammatory bowel disease, Hepatitis C, Leukaemia, Lymphoma, Solid organ cancer malignancy.
#44 Erythema multiforme in children | The College of Family Physicians of Canada
https://www.cfp.ca/content/68/7/507
Erythema multiforme (EM) is an immune-mediated, mucocutaneous condition frequently characterized by target lesions mostly involving the skin but also, at times, involving the mucous membranes (oral, ocular, or genital mucosa). These are annular macules, which later become papules, not infrequently coalescing to plaques. […] The causes of EM are mostly viral (80% to 90%) or drug related. Herpes simplex virus type 1 is the most commonly identified cause; other implicated viruses include herpes simplex virus type 2, cytomegalovirus, Epstein-Barr virus (infectious mononucleosis), influenza, and most recently COVID-19 (mostly in patients younger than 30 years or older than 55 years). Vulvovaginal candidiasis and mycoplasma pneumonia are also associated with EM. […] Medications that may trigger the appearance of EM include antibiotics (eg, erythromycin, nitrofurantoin, penicillins, sulfonamides, tetracyclines), antiepileptic medications, nonsteroidal anti-inflammatory drugs, and vaccines (which are the most common cause in young infants). Other conditions associated with EM are inflammatory bowel disease, hepatitis C, leukemia, lymphoma, and solid-organ cancer malignancy.
#45 Erythema Multiforme: Recognition and Management | AAFP
https://www.aafp.org/pubs/afp/issues/2019/0715/p82.html
Vaccines such as measles, mumps, and rubella; smallpox; hepatitis B; meningococcal; pneumococcal; varicella; influenza; and Haemophilus influenzae have also been associated with erythema multiforme, although incidence is low. Less commonly, erythema multiforme has been associated with autoimmune diseases, such as inflammatory bowel disease and malignancies, specifically leukemia and lymphoma. Persistent erythema multiforme and refractory erythema multiforme have been found in patients with solid organ cancers, such as renal cell carcinoma and gastric adenocarcinoma.
#46 Erythema multiforme: Pictures, causes, treatment, and more
https://www.medicalnewstoday.com/articles/323801
Other rare causes include vaccines and cancers. Vaccines associated with erythema multiforme include the MMR (measles, mumps, and rubella) vaccine, and those for smallpox, hepatitis B, varicella, and influenza. Cancers such as leukemia, lymphoma, renal cell carcinoma, and gastric adenocarcinoma have been linked to erythema multiforme.
#47 Erythema multiforme – DermNet
https://dermnetnz.org/topics/erythema-multiforme
Erythema multiforme is precipitated by herpes simplex virus (HSV) infection; alternative triggers include other infections, medications, and vaccinations. […] Infection precipitates 90% of cases, with HSV type 1 being the predominant cause. Other infectious triggers include: HSV type 2, Cytomegalovirus, Epstein-Barr virus, Influenza virus, Vulvovaginal candidiasis, SARS-CoV-2, Orf. […] Medications which may trigger erythema multiforme include: Antibiotics (including erythromycin, nitrofurantoin, penicillins, sulfonamides, and tetracyclines), Anti-epileptics, Non-steroidal anti-inflammatory drugs, Vaccinations (most common cause in infants). […] Other conditions associated with erythema multiforme (usually in persistent disease) include: Inflammatory bowel disease, Hepatitis C, Leukaemia, Lymphoma, Solid organ cancer malignancy.
#48 Erythema multiforme in children | The College of Family Physicians of Canada
https://www.cfp.ca/content/68/7/507
Erythema multiforme (EM) is an immune-mediated, mucocutaneous condition frequently characterized by target lesions mostly involving the skin but also, at times, involving the mucous membranes (oral, ocular, or genital mucosa). These are annular macules, which later become papules, not infrequently coalescing to plaques. […] The causes of EM are mostly viral (80% to 90%) or drug related. Herpes simplex virus type 1 is the most commonly identified cause; other implicated viruses include herpes simplex virus type 2, cytomegalovirus, Epstein-Barr virus (infectious mononucleosis), influenza, and most recently COVID-19 (mostly in patients younger than 30 years or older than 55 years). Vulvovaginal candidiasis and mycoplasma pneumonia are also associated with EM. […] Medications that may trigger the appearance of EM include antibiotics (eg, erythromycin, nitrofurantoin, penicillins, sulfonamides, tetracyclines), antiepileptic medications, nonsteroidal anti-inflammatory drugs, and vaccines (which are the most common cause in young infants). Other conditions associated with EM are inflammatory bowel disease, hepatitis C, leukemia, lymphoma, and solid-organ cancer malignancy.
#49 Erythema Multiforme – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470259/
Moreover, a strong association between the COVID-19 vaccine and erythema multiforme has recently been found. […] Autoimmune conditions (eg, systemic lupus erythematosus) are also associated with erythema multiforme, particularly causing a typical but rare syndrome called Rowell syndrome. […] Another common cause of erythema multiforme, particularly in children, is Mycoplasma pneumoniae infection. […] Although herpes simplex virus (HSV) types 1 and 2 and Mycoplasma pneumonia are the common causes of erythema multiforme, many other viral, fungal, and bacterial infections have been implicated. […] Human immunodeficiency virus (HIV) infection and HIV treatment medications have been found to have a direct or indirect effect on the development of erythema multiforme. […] Also, various vaccines leading to erythema multiforme have been reported, including Bacille Calmette-Gurin, oral polio, vaccinia, and tetanus/diphtheria vaccines. […] Drugs associated with erythema multiforme include antibiotics (eg, penicillins, cephalosporins, macrolides, and sulfonamides), antituberculosis agents, and antipyretics.
#50 Erythema Multiforme: Symptoms, Causes, Diagnosis, Treatment
https://www.verywellhealth.com/erythema-multiforme-7092731
Reactions to medications can also cause EM. The severe form of EM is often caused by medication rather than infection. […] Medication triggers for EM may include: Antibiotics (such as sulfonamides, tetracyclines, penicillins, amoxicillin, and ampicillin), Nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil/Motrin (ibuprofen), Anticonvulsants/antiepileptics (such as phenytoin and barbiturates), Some vaccines, Anesthesia, Allopurinol (used for gout). […] Some medical conditions associated with EM include: Inflammatory bowel disease (Crohn’s disease and ulcerative colitis), Systemic lupus erythematosus (lupus, an autoimmune disease), Hepatitis C (causes liver inflammation that can lead to liver damage), Leukemia (blood cancers), Lymphoma (cancers starting in the lymph system), Solid organ cancer malignancy.
#51 Erythema Multiforme Causes
https://mobile.fpnotebook.com/ENT/Derm/ErythmMltfrmCs.htm
Risk of Erythema Multiforme Major with Trimethoprim-Sulfamethoxazole is up to 40 fold higher in HIV […] Miscellaneous Medications […] Autoimmune Conditions […] Neoplasm […] Associated with Leukemia, Lymphoma […] Solid organ neoplasms (Renal Cell Carcinoma, Gastric Adenocarcinoma) may cause persistent and refractory cases […] May also be associated with Radiotherapy.
#52 Recent Updates in the Treatment of Erythema Multiforme
https://www.mdpi.com/1648-9144/57/9/921
A rarer type of EM is known as persistent EM, which is defined by the continuous appearance of EM lesions with marked resistance to therapy. Lesions are typically widespread and are, by definition, uninterrupted. Cases of persistent EM have been associated with underlying malignancies, inflammatory bowel disease, as well as infections with EpsteinâBarr virus, cytomegalovirus, hepatitis C virus, and influenza.
#53 Erythema Multiforme – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK470259/
Erythema multiforme is an immune-mediated hypersensitivity reaction affecting both the skin and mucous membranes, characterized by the appearance of macular, papular, or bullous lesions that often form distinct „target lesions,” primarily found on the extremities. […] Erythema multiforme is most often triggered by infections, particularly herpes simplex virus, but can also be caused by medications, autoimmune disorders, and occasionally vaccines. […] Erythema multiforme’s etiologies are variable and numerous, and its clinical course is generally favorable. […] The etiology of erythema multiforme is multifactorial, including infections, medications, autoimmune disease, malignancy, immunizations, radiation exposure, allergic contact dermatitis, sarcoidosis, and menstruation. […] Approximately 90% of cases of erythema multiforme are caused by infections (viral, bacterial, or fungal), with herpes simplex virus being the most common culprit.
#54 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
The following have also been reported as causes of EM: Flavorings and preservatives (eg, benzoic acid and cinnamon), Immunologic disorders (eg, transient selective C4 deficiency of infancy, collagen diseases, vasculitides, sarcoidosis, non-Hodgkin lymphoma, leukemia, multiple myeloma, myeloid metaplasia, and polycythemia), Physical or mechanical factors (eg, tattooing, radiotherapy, cold, and sunlight), Foods (eg, salmon berries and margarine), Malignancy, Hormonal factors.
#55 Erythema multiforme – WikEM
https://wikem.org/wiki/Erythema_multiforme
Erythema Multiforme (EM) is an acute, self-limited skin condition […] Despite multiple associations, thought to be triggered by HSV in most cases […] HSV responsible for ~70% of cases, making it the most common etiology. […] Infections: Viral: HSV, hepatitis, influenza A […] Drugs: Antibiotics (penicillin, sulfonamides), anticonvulsants (phenytoin, barbiturates), NSAIDS, aspirin, anti-tuberculosis meds, allopurinol, etc. […] Collagen Vascular Disorders: RA, SLE, dermatomyositis, polyarteritis nodosa. […] Others: Pregnancy, cold weather, sunlight, contact exposure, foods, malignancy, hormonal.
#56 A case of erythema multiforme with unknown etiology
https://www.oatext.com/a-case-of-erythema-multiforme-with-unknown-etiology.php
Erythema Multiforme Major is an acute inflammatory hypersensitivity reaction usually due to infections and to medications. […] Erythema multiforme major is an acute hypersensitive reaction that can be seen at all ages due to medications and infections such as herpes simplex virus and mycoplasma pneumonia. […] No etiology can be detected in 25-50% of the cases. […] The etiological cause could not have detected in present case, either. […] Erythema Multiforme Major could be associated with anemia, lymphopenia, leukocytosis, elevated ESR and impaired kidney functions. […] In conclusion, Erythema Multiforme Major is a toxic hypersensitivity reaction with a rapid course.
#57 Erythema Information | Mount Sinai – New York
https://www.mountsinai.org/health-library/condition/erythema
In half of all cases of either erythema multiforme or erythema nodosum, the exact cause is not known. […] Erythema multiforme: Infection, primarily from the herpes simplex virus (HSV). […] Erythema multiforme: Medications, such as penicillin and sulfa drugs; antiseizure medications; nonsteroidal anti-inflammatory drugs (NSAIDs).
#58
https://step2.medbullets.com/dermatology/120087/erythema-multiforme
Common, acute mucocutaneous disease with classic target-shaped lesions with symmetric distribution. […] Most common = infection. […] Herpes simplex virus (most common cause). […] Mycoplasma pneumonia. […] Upper respiratory infections. […] Less common = drugs. […] Erythema multiforme (EM) major and minor. […] Major: involves mucous membranes and systemic signs. […] Minor: no mucous membrane involvement and no systemic signs. […] Idiopathic.
#59 Erythema multiforme – Dermatology Advisor
https://www.dermatologyadvisor.com/home/decision-support-in-medicine/pediatrics/erythema-multiforme/
Other medications: progesterone, gemfibrozil, methotrexate, barium contrast medium […] EM can be seen at any age and has no sex or racial predilection. […] There is likely a genetic predisposition to EM. HLA B-15, HLA Aw33, HLA DRw53, and HLA DQB-1 and HLA DQ3 have been associated. […] It is unclear how HSV induces EM, but the virus can be found by PCR in the acral lesions of EM. […] EM minor is most commonly caused by HSV, so prevention of flares of HSV may prevent flares of EM.
#60 Erythema Multiforme in Mouth: Symptoms, Causes, and More
https://www.healthline.com/health/erythema-multiforme-in-mouth
Erythema multiforme is an immune-mediated skin condition that may develop inside the mouth. […] In about 90% of cases, erythema multiforme develops following an infection. Herpes simplex virus (HSV) is the most common infection associated with the condition. […] More commonly, HSV-1 causes erythema multiforme. However, it can also develop as a result of HSV-2 infection. […] As erythema multiforme is a rare complication of HSV, its possible that theres also a genetic component. […] Although less common, other possible causes include certain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, antiepileptic drugs, and some vaccinations, particularly in infants. […] Other possible causes include hepatitis C and other infections, and systemic lupus erythematosus (SLE). […] Herpes simplex virus (HSV) infection is the main cause of erythema multiforme. Some medications and other infections can also lead to erythema multiforme.
#61 Erythema multiforme – Wikipedia
https://en.wikipedia.org/wiki/Erythema_multiforme
Erythema multiforme (EM) is an immune-mediated inflammatory skin condition associated with several viral infections, that appears with red patches evolving into target lesions, typically on both hands. It is typically associated with infection by either herpes simplex virus or Mycoplasma pneumoniae. […] Erythema multiforme typically arises as a type IV hypersensitivity reaction to certain infections or, rarely, certain medications. The most common trigger is an infection with any type of the herpes simplex virus. The second most common trigger, and the most common in children, is infection with Mycoplasma pneumoniae, most commonly as an atypical pneumonia. […] The pathogenic immune response in EM involves both CD4+ helper T cells and CD8+ cytotoxic T cells, which orchestrate a type IV hypersensitivity reaction.
#62
https://www.jpad.com.pk/index.php/jpad/article/view/2403
Erythema multiforme is a common reactive skin disease to different endogenous and exogenous triggers with characteristic clinical features of variable severity. […] Erythema multiforme with mucous membrane involvement and Stevens-Johnson syndrome are clinically different disorders with distinct causes. […] Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions.
#63 Erythema multiforme – DermNet
https://dermnetnz.org/topics/erythema-multiforme
In many cases, the inciting factor remains unknown. […] Most research on the mechanism of disease has focused on the herpes-associated presentation. The herpes virus is phagocytosed by mononuclear cells which express cutaneous lymphocyte antigen (a skin-homing receptor). Engulfed viral DNA is then transferred to the epidermis and into keratinocytes. Within the keratinocyte layer, expression of viral DNA fragments induces a cell-mediated immune response, including the production of interferon- which upregulates the inflammatory process.
#64 Erythema multiforme – Wikipedia
https://en.wikipedia.org/wiki/Erythema_multiforme
Rarely, some patients may suffer from a persistent and treatment-resistant form of erythema multiforme caused by the Epstein-Barr virus. […] Herpes simplex virus (HSV) is by far the most frequent cause of erythema multiforme. HSV DNA is also detected in nearly half of patients with idiopathic EM, suggesting that the true frequency is even higher than traditionally thought. […] 100% of HSV-associated EM cases are found to have DNA for viral-type DNA polymerase (Pol) gene within keratinocytes. Despite this association, an active and infectious form of HSV has never been found in a patient suffering from EM, indicating that it is exclusively a post-viral hypersensitivity syndrome in these patients, rather than a symptom of the virus itself.
#65 Erythema multiforme: a case series and review of literature – MedCrave online
https://medcraveonline.com/OAJTMR/erythema-multiforme-a-case-series-and-review-of-literature.html
Unlike virus-induced EM, mechanism of damage in drug-induced EM does not appear to be a result of the delayed type of hypersensitivity. In drug-induced EM, reactive metabolites of the particular drug induce the disease and keratinocyte apoptosis is induced by tumor necrosis factor alpha (TNF-) released from keratinocytes, macrophages, and monocytes leading to tissue damage.
#66 Erythema Multiforme | AAFP
https://www.aafp.org/pubs/afp/issues/2006/1201/p1883.html
Erythema multiforme is a skin condition considered to be a hypersensitivity reaction to infections or drugs. […] Erythema multiforme usually occurs in adults 20 to 40 years of age, although it can occur in patients of all ages. Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50 percent of cases. Mycoplasma pneumoniae is another commonly reported etiology, especially in children, as is fungal infection. The medications most often associated with erythema multiforme are barbiturates, hydantoins, nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, and sulfonamides. […] Recurrent erythema multiforme often is secondary to HSV-1 and -2 reactivation, although the HSV may be clinically silent. […] The pathogenesis of herpes-associated erythema multiforme has been well studied and is consistent with a delayed-type hypersensitivity reaction. […] Drug-associated erythema multiforme lesions test positive for tumor necrosis factor and not interferon- as in herpes-associated erythema multiforme lesions, suggesting a varying mechanism.
#67 Erythema multiforme: Pathogenesis, clinical features, and diagnosis – UpToDate
https://www.uptodate.com/contents/erythema-multiforme-pathogenesis-clinical-features-and-diagnosis
Erythema multiforme (EM) is an acute, immune-mediated condition characterized by the appearance of distinctive target-like lesions on the skin. A variety of factors have been implicated in the pathogenesis of EM. The disorder is most commonly induced by infection, with herpes simplex virus being the most frequent precipitator. […] However, in a minority of cases, the disease recurs frequently over the course of years.
#68 Erythema Multiforme | AAFP
https://www.aafp.org/pubs/afp/issues/2006/1201/p1883.html
Erythema multiforme is a skin condition considered to be a hypersensitivity reaction to infections or drugs. […] Erythema multiforme usually occurs in adults 20 to 40 years of age, although it can occur in patients of all ages. Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50 percent of cases. Mycoplasma pneumoniae is another commonly reported etiology, especially in children, as is fungal infection. The medications most often associated with erythema multiforme are barbiturates, hydantoins, nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, and sulfonamides. […] Recurrent erythema multiforme often is secondary to HSV-1 and -2 reactivation, although the HSV may be clinically silent. […] The pathogenesis of herpes-associated erythema multiforme has been well studied and is consistent with a delayed-type hypersensitivity reaction. […] Drug-associated erythema multiforme lesions test positive for tumor necrosis factor and not interferon- as in herpes-associated erythema multiforme lesions, suggesting a varying mechanism.
#69 Erythema Multiforme Pictures and Diagnosis Guidelines
https://ostrowonline.usc.edu/what-is-erythema-multiforme/
Erythema Multiforme causes lesions of the mucous membranes and the skin. This is autoimmune but its thought to be more of a hypersensitivity-type reaction or immune complex condition. Its not the same etiology as the other vesiculobullous conditions we talked about like mucous membrane pemphigoid. […] If its recurrent it is oftentimes secondary to herpes reactivation and as the bodys response to herpes reactivation.
#70 Recent Updates in the Treatment of Erythema Multiforme
https://www.mdpi.com/1648-9144/57/9/921
A rarer type of EM is known as persistent EM, which is defined by the continuous appearance of EM lesions with marked resistance to therapy. Lesions are typically widespread and are, by definition, uninterrupted. Cases of persistent EM have been associated with underlying malignancies, inflammatory bowel disease, as well as infections with EpsteinâBarr virus, cytomegalovirus, hepatitis C virus, and influenza.
#71 Erythema Multiforme: Background, Pathophysiology, Etiology
https://emedicine.medscape.com/article/1122915-overview
Erythema multiforme (EM) is an acute, self-limited, and sometimes recurring skin condition that is considered to be a type IV hypersensitivity reaction associated with certain infections, medications, and various other triggers. […] Precipitating factors include herpes simplex virus (HSV), Epstein-Barr virus (EBV), and histoplasmosis. […] More than 50% of all cases are attributed to medications. […] Many suspected etiologic factors have been reported to cause EM. Both EM and SJS may be induced by medications, but infectious agents are also considered to be a major cause of EM. […] Other reported risk factors include male sex and a previous history of EM; pregnancy may contribute to the development of EM as well. […] Infectious causes are more common in children and are implicated commonly in EM.
#72 Erythema Multiforme | AAFP
https://www.aafp.org/pubs/afp/issues/2006/1201/p1883.html
Erythema multiforme is a skin condition considered to be a hypersensitivity reaction to infections or drugs. […] Erythema multiforme usually occurs in adults 20 to 40 years of age, although it can occur in patients of all ages. Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50 percent of cases. Mycoplasma pneumoniae is another commonly reported etiology, especially in children, as is fungal infection. The medications most often associated with erythema multiforme are barbiturates, hydantoins, nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, and sulfonamides. […] Recurrent erythema multiforme often is secondary to HSV-1 and -2 reactivation, although the HSV may be clinically silent. […] The pathogenesis of herpes-associated erythema multiforme has been well studied and is consistent with a delayed-type hypersensitivity reaction. […] Drug-associated erythema multiforme lesions test positive for tumor necrosis factor and not interferon- as in herpes-associated erythema multiforme lesions, suggesting a varying mechanism.
#73 Paediatric Erythema Multiforme: Epidemiological, Clinical and Laboratory Characteristics | HTML | Acta Dermato-Venereologica
https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2569
In our study, medications were associated with EM in only 16% of cases. […] In our cohort, the mean age of affected children with EM was 11.34.4 years, ranging from 4 to 18 years. […] We did not identify other specific viral pathogens as possible triggers for EM; however, more than one-third of patients reported a recent non-specific febrile illness prior to the appearance of EM, which may have been a viral infection. […] Four of our patients were shown to have an infection with M. pneumoniae. […] It should be noted that we observed a high rate of C-reactive protein (CRP) and/or erythrocyte sedimentation rate in our study. […] The most important findings of this study are the lack of EM in infants and toddlers 4 years and the high rate of misdiagnosis, especially in patients with UM, in this age group.
#74 Erythema Multiforme: Recognition and Management – PubMed
https://pubmed.ncbi.nlm.nih.gov/31305041/
Erythema multiforme is an immune-mediated reaction that involves the skin and sometimes the mucosa. […] Infections, especially herpes simplex virus and Mycoplasma pneumoniae, and medications constitute most of the causes of erythema multiforme; immunizations and autoimmune diseases have also been linked to erythema multiforme. […] The management of erythema multiforme involves symptomatic treatment with topical steroids or antihistamines and treating the underlying etiology, if known.
#75 Erythema multiforme
https://www.pcds.org.uk/clinical-guidance/erythema-multiforme
Erythema multiforme (EM) is a hypersensitivity reaction usually triggered by infections, most commonly herpes simplex virus. EM appears to be caused by an immunological reaction to numerous triggers, although in up to 50% of cases no provoking factor is identified. Herpes simplex virus (HSV type 1 is more commonly associated than type 2) is the most common cause, and usually precedes the skin eruption by 3-14 days, although the infection can be subclinical. Mycoplasma pneumonia is the next most common trigger. There are many other identifiable triggers including viral infections eg the parapoxvirus (orf, milkers’ nodules), varicella (chickenpox, shingles), Hepatitis B, bacterial infections eg Rickettsia, fungal infections eg tinea. Drugs probably account for less than 10% of EM cases. While many drugs have been implicated, eg antibiotics, NSAID and sulphonamides, too often the evidence is inadequate to be certain if the drug was the cause. […] Recurrent EM secondary to herpes simplex should be treated with prophylactic oral aciclovir. If EM is felt to be secondary to a drug, then it should be withdrawn.
#76 Erythema multiforme
https://www.nhs.uk/conditions/erythema-multiforme/
Erythema multiforme is a skin condition that can be caused by an infection or some medicines. […] Erythema multiforme is usually caused by an infection, such as the herpes simplex virus (which also causes cold sores) or a bacteria that causes lung conditions like pneumonia. […] It can sometimes be caused by some vaccines or medicines such as non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, statins and medicines for epilepsy. […] If it’s caused by a medicine, you usually need to stop taking it. But do not stop taking any medicines without talking to a doctor first.
#77 Erythema Multiforme: Symptoms and Treatment | Doctor
https://patient.info/doctor/erythema-multiforme-pro
Erythema multiforme (EM) is a skin condition due to an immune-mediated hypersensitivity reaction to infections or drugs. […] 90% of cases of erythema multiforme are caused by infections. […] Herpes simplex virus (HSV) 1 and 2 infections (account for 50% of cases). […] Other viruses (varicella-zoster virus, cytomegalovirus, hepatitis C virus, and HIV). […] If a drug is thought to be responsible, it must be withdrawn. If an infection is suspected, it should be treated.