2.03 Reactive Erythemas PDF

DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble...

DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 OVERVIEW:  Centripetal: outside -> inside  It measures from a few millimeters to approximately  Erythema Multiforme 3 cm and may expand slightly over 24 to 48 a.EM Major hours. Although the periphery remains erythem- b.EM Minor atous and edematous, the center becomes  Epidermal Necrolysis violaceous and dark; inflammatory activity may a.SJS regress or relapse in the center, which gives rise to b.TEN concentric rings of color  Often, the center turns purpuric or necrotic or transforms into a tense vesicle or bulla. The result is I. ERYTHEMA MULTIFORME the classic target or iris lesion.  Acute mucocutaneous syndrome  Course is usually mild and self- limited but carries a risk of relapse  EM is separated into: EM minor: Skin +/- mild mucosal involvement EM major: skin + mucous membranes  CUTANEOUS FEATURES  Arises abruptly (within 3 days)  Symmetric and spread centripetally  (+) Koebner phenomenon  (+) actinic predilection  Highly regular, circular, wheal-like erythematous papule or plaque  Three concentric components: 1. a dusky central disk or blister 2. an infiltrated pale ring 3. an erythematous halo  TREATMENT  Systemic corticosteroids shorten the duration of fever and eruption, especially swelling and pain of the mucosae but may increase the length of hospitalization because of complications  Oral antihistamines  Topical corticosteroids 1 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023  Liquid antacids  Diuretics and oral antidiabetics with sulfonamide  Topical glucocorticoids structure do not appear to be risk factors for  Local anesthetics SJS/TEN.  Ocular lubricant  RECOMMENDATIONS  An interval of 4–28 days between beginning of  COURSE AND PROGNOSIS drug use and onset of the adverse reaction is  Usually run a mild course most suggestive of an association  Recurrences are common  When patients are exposed to several medications  Each individual attack subsides within 1 to 4 with high expected benefits, the timing of weeks administration is important to determine which one(s)  Recovery is complete, and there are usually no must be stopped and if some may be continued or sequelae, except for transient skin discoloration. reintroduced  Ocular erosions of EMM may cause severe residual  The risks of various antibiotics to induce SJS/TEN are scarring within the same order of magnitude but substantially  M. pneumoniae–related EMM may be associated with lower than the risk of anti-infective sulfonamides. severe erosive bronchitis  No chance of skin failure  CUTANEOUS LESIONS II. EPIDERMAL NECROLYSIS  Rare life threatening reaction  Mainly induced by medication - More than 20% remain idiopathic or caused by infection  Widespread apoptosis of keratinocytes is provoked by the activation of a cell-mediated cytotoxic reaction and amplified by cytokines, mainly granulysin.  confluent purpuric and erythematous macules evolving to flaccid blisters and epidermal detachment often start on the upper trunk and spread to the limbs associated with mucous membrane involvement  Histopathology shows full-thickness necrosis of epidermis associated with mild mononuclear cell infiltrate.  DRUGS  Their use should be carefully evaluated, and they should be suspected promptly.  Allopurinol  Aminopenicillins  Eruption is initially symmetrical on the face, upper  Antiretrovirals (esp NNRTIs- Nevirapine, trunk, and proximal extremities Efaverenz, Etravirine)  Initial skin lesions are characterized by  Lamotrigine erythematous, dusky red, irregularly shaped  Cotrimoxazole (and other antiinfective purpuric macules, which progressively coalesce sulfonamides and sulfasalazine)  (+) Nikolsky sign  Carbamazepine  Distal portions of the arms as well as the legs are  Cephalosporin relatively spared, but the eruption can rapidly extend  NSAIDs (oxicam type, eg, meloxicam) to the rest of the body within a few days and even  Phenobarbital within a few hours  Phenytoin  Atypical target lesions with dark centers are often  Quinolones observed  Sulfonamides (Sulfamethoxazole, Sulfadiazine,  Confluence of necrotic lesions leads to extensive and Sulfasalazine) diffuse erythema. Nikolsky sign, or dislodgement of  Valproic acid does not seem to have an increased the epidermis by lateral pressure, is positive on risk for SJS/TEN in contrast to other antiepileptics. erythematous zones 2 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023  MUCOUS MEMBRANE INVOLVEMENT  Mucous membrane involvement (nearly always on at least two sites) is observed in approximately 90% of cases and can precede or follow the skin eruption.  begins with erythema followed by painful erosions of the oral, ocular, genital, nasal, anal and sometimes tracheal or bronchial mucosa. This usually leads to impaired alimentation, photophobia, conjunctivitis, and painful micturition.  oral cavity and the vermilion border of the lips are almost invariably affected and feature painful hemorrhagic erosions coated by grayish white pseudomembranes and hemorrhagic crusts of the lips  Approximately 80% of patients have conjunctival  Based upon surface area of EPIDERMAL lesions, mainly manifested by pain, photophobia, DETACHMENT or (+) NIKOLSKY SIGN lacrimation, redness, and discharge. Severe  Patients are classified into one of three groups forms may lead to epithelial defect and corneal according to the total area in which the ulceration, anterior uveitis, and purulent epidermis is detached or “detachable” (positive Nikolsky): (1) SJS, less than 10% of body surface area (BSA); (2) SJS– TEN overlap, between 10% and 30%; (3) TEN, more than 30% of BSA Course of epidermal necrolysis (EN)  First symptoms of the reaction are unspecific like fever, sore throat, and reduced state of health (prodromal symptoms). Medications given for the prodromal symptoms are not associated with EN 3 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 even if the first clear sign (mucosal involvement, macules) appears after their intake (“protopathic bias”; 1-3D). After admission the progression of EN to maximum skin detachment continues for up to 5 days (5D)  The epidermal detachment progresses for 5 to 7 days. Then patients enter a plateau phase, which corresponds to progressive re-epithelialization. This can take a few days to a few weeks, depending on the severity of the disease and the prior general condition of the patient. During this period, life- threatening complications such as sepsis or systemic organ failure may occur.  Approach to Patient with SJS/TEN  In most recent Fitzpatrick textbook, IVIG is no longer advised  Steroids still remain controversial- Medium doses for short periods (days rather than weeks) may be benefificial  Cyclosporine A- Early administration may halt the progression of skin detachment and increase survival  Anti-TNF monoclonal antibodies- Extreme caution is advised  SCORTEN: Prognostic Scoring NOTE: SERUM BICARB dapat < 4 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 5 | Page TRANSCRIBERS: Jay-G  DERMA Pines City Colleges- Doctor of Medicine 2.03 REACTIVE ERYTHEMAS 308 Lecturer: Dr. Rita Chan Noble Date: October 2, 2023 6 | Page TRANSCRIBERS: Jay-G  PCCSOM 2026 DERMATOLOGY M.03 REACTIVE ERYTHEMAS Mast cells and their histamine play a crucial role in the DERMATOLOGY LECTURE pathogenicity LECTURER: RITA CHAN NOBLE, MD, DPDS Autoantibodies against IgE or the high-affinity IgE receptor (FcεRI) that activate mast cells and basophils TOPIC OUTLINE and induce histamine release may be detected in up to URTICARIA half of patients ERYTHEMA MULTIFORME  EM MAJOR Angioedema  EM MINOR EPIDERMAL NECROLYSIS  SJS  TEN URTICARIA Hives Local and transient skin or mucosal edema that develops in deep tissues Mostly without itching May accompany pain or burning sensations. Mediated by bradykinin rather than histamine Local erythematous wheals with itchy sensations Diminish within 1 day May occur spontaneously (spontaneous or idiopathic urticaria) or in response to specific stimuli Acute: less than 6 weeks Chronic: more than 6 weeks NOTE TAKER: COLLO Page 1 | 5  PCCSOM 2026 DERMATOLOGY M.03 REACTIVE ERYTHEMAS ERYTHEMA MULTIFORME Acute mucocutaneous syndrome EM is separated into:  EM Minor ○ Skin +/- mild mucosal involvement  EM major ○ Skin + mucous membranes CUTANEOUS FEATURES Arises abruptly (within 3 days) Symmetric and spread centripetally (+) Koebner phenomenon (+) actinic predilection Highly regular, circular, wheal-like erythematous papule or plaque Centripetal: outside -> inside Three concentric Fig. It measures from a few Potential Causes for Episodic/ Acute Urticaria millimeters to approximately components: Foods: allergens such as milk and eggs (for infants), nuts, 3 cm and may expand slightly  (1) a dusky central seeds, fruits, and seafood (for adults) and pseudoallergens over 24 to 48 hours. Although disk or blister (food additives, salicylates, histamine, and other amines) the periphery remains  (2) an infiltrated Drugs: antibiotics (β-lactams, vancomycin, polymyxin B), erythem- atous and pale ring NSAIDs (oral, injection, topical), opioids, contrast media, edematous, the center  (3) an opioids, ACE inhibitors (for angioedema) becomes violaceous and dark; erythematous halo Vaccines inflammatory activity may Blood products: transfusions regress or relapse in the Stings: bee, wasp venoms center, which gives rise to Contactants: latex, chemicals concentric rings of color. Inhalants: latex powder, chemicals Often, the center turns purpuric or necrotic or transforms into a tense vesicle or bulla. The result is the classic target or iris lesion. NOTE TAKER: COLLO Page 2 | 5  PCCSOM 2026 DERMATOLOGY M.03 REACTIVE ERYTHEMAS EPIDERMAL NECROLYSIS Rare Life threatening Mainly induced by medication ○ 20% are idiopathic or caused by infection Apoptosis of keratinocytes is provoked by the activation of a cell-mediated cytotoxic reaction Epidermal necrolysis is a rare life-threatening reaction mainly induced by medication Widespread apoptosis of keratinocytes is provoked by the activation of a cell-mediated cytotoxic reaction and amplified by cytokines, mainly granulysin. Histopathology shows full-thickness necrosis of epidermis associated with mild mononuclear cell infiltrate. DRUGS: Their use should be carefully evaluated, and they should be suspected promptly.  Allopurinol  Aminopenicillins  Antiretrovirals (esp NNRTIs- Nevirapine, Efaverenz, Etravirine)  Lamotrigine  Cotrimoxazole (and other antiinfective sulfonamides and sulfasalazine) TREATMENT:  Carbamazepine Systemic corticosteroids shorten the duration of fever  Cephalosporin and eruption, especially swelling and pain of the  NSAIDs (oxicam type, eg, meloxicam) mucosae but may increase the length of hospitalization  Phenobarbital because of complications  Phenytoin Oral antihistamines  Quinolones Topical corticosteroids  Sulfonamides (Sulfamethoxazole, Sulfadiazine, Liquid antacids Sulfasalazine) Topical glucocorticoids RECOMMENDATIONS: Local anesthetics An interval of 4–28 days between beginning of drug Ocular lubricant use and onset of the adverse reaction is most COURSE AND PROGNOSIS: suggestive of an association Usually run a mild course When patients are exposed to several medications Recurrences are common with high expected benefits, the timing of Each individual attack subsides within 1 to 4 weeks administration is important to determine which one(s) Recovery is complete, usually no sequelae, except for must be stopped and if some may be continued or transient discoloration. reintroduced Ocular erosions of EMM may cause severe residual The risks of various antibiotics to induce SJS/TEN are scarring within the same order of magnitude but substantially M. pneumoniae–related EMM may be associated with lower than the risk of anti-infective sulfonamides. severe erosive bronchitis Valproic acid does not seem to have an increased risk No chance of skin failure for SJS/TEN in contrast to other antiepileptics. Diuretics and oral antidiabetics with sulfonamide structure do not appear to be risk factors for SJS/TEN. NOTE TAKER: COLLO Page 3 | 5  PCCSOM 2026 CUTANEOUS LESIONS: DERMATOLOGY M.03 REACTIVE ERYTHEMAS (2) SJS– TEN overlap, Eruption is initially between 10% and 30%; symmetrical on the (3) TEN, more than 30% of face, upper trunk, and BSA. proximal extremities Initial lesions are erythematous, dusky red, irregularly shaped purpuric macules, which progressively coalesce and evolve to flaccid blisters and epidermal detachment Associated with mucous membrane involvement (+) Nikolsky sign MUCOUS MEMBRANE INVOLVEMENT At least 2 sites oral cavity and the vermilion border of the lips SPECTRUM OF DISEASE 80% have conjunctival lesions Mucous membrane involvement (nearly always on at least two sites) is observed in approximately 90% of cases and can precede or follow the skin eruption. begins with erythema followed by painful erosions of the oral, ocular, genital, nasal, anal and sometimes tracheal or bronchial mucosa. This usually leads to impaired alimentation, photophobia, conjunctivitis, and painful Based upon surface area of EPIDERMAL DETACHMENT or micturition. (+) NIKOLSKY SIGN Distal portions of the arms Confluence of necrotic The oral cavity and the vermilion border of the lips are as well as the legs are lesions leads to extensive almost invariably affected and feature painful hemorrhagic relatively spared, but the and diffuse erythema. erosions coated by grayish white pseudomembranes and eruption can rapidly extend Nikolsky sign, or hemorrhagic crusts of the lips to the rest of the body dislodgement of the within a few days and even epidermis by lateral Approximately 80% of patients have conjunctival lesions, within a few hours. pressure, is positive on mainly manifested by pain, photophobia, lacrimation, erythematous zones. redness, and discharge. Severe forms may lead to The initial skin lesions are epithelial defect and corneal ulceration, anterior uveitis, characterized by Patients are classified into and purulent. erythematous, dusky red, one of three groups irregularly shaped purpuric according to the total area macules, which in which the epidermis is progressively coalesce. detached or “detachable” Atypical target lesions with (positive Nikolsky): (1) SJS, dark centers are often less than 10% of body observed surface area (BSA); NOTE TAKER: COLLO Page 4 | 5  PCCSOM 2026 DERMATOLOGY M.03 REACTIVE ERYTHEMAS CHECKPOINT: 1. An interval of ______ between beginning of drug use and onset of the adverse reaction is most suggestive of an association A. 3-27 days B. 4–28 days - C. 5-25 days Course of epidermal necrolysis (EN). D. 7-35 days First symptoms of the reaction are unspecific like fever, 2. Which is not a cutaneous feature of erythema sore throat, and reduced state of health (prodromal multiforme? symptoms). Medications given for the prodromal A. arises abruptly (within a day)- symptoms are not associated with EN even if the first clear B. a dusky central disk or blister sign (mucosal involvement, macules) appears after their C. an erythematous halo intake (“protopathic bias”; 1-3D). After admission the D. symmetric and spread centripetally progression of EN to maximum skin detachment continues 3. True or False? Epidermal necrolysis’ initial lesions are for up to 5 days (5D). erythematous, dusky red, irregularly shaped purpuric Approach to Patient with SJS/TEN macules, which progressively coalesce and evolve to flaccid blisters and epidermal detachment.  In most recent Fitzpatrick textbook, IVIG is no longer advised 4. True or False? Epidermal necrolysis is common and  Steroids still remain controversial- Medium doses for life threatening. short periods (days rather than weeks) may be 5. Diagnosis? beneficial  Cyclosporine A- Early administration may halt the progression of skin detachment and increase survival  Anti-TNF monoclonal antibodies- Extreme caution is advised SCORTEN: Prognostic Scoring B, A (W/N 3DAYS, TRUE, FALSE (RARE), ANGIOEDEMA NOTE TAKER: COLLO Page 5 | 5