Dermatologic Emergencies, Drug Eruption, Blistering Disorders 426 C1 + 428 C2 Notes Dr

Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani Dermatologic Emergencies, Drug Eruption, Blistering disorders Dr. Mona Al-Halawani

DERMATOLOGIC EMERGENCIES: These are some dermatologic emergencies:  Burn and burn like lesions e.g. cutaneous lymphoma if it presents like Erythroderma.  Pustular psoriasis can present like septic shock (fever, rigor, shivering).  Erythrodermic psoriasis.  Acne Fulminant. Treatment is systemic steroids.  Acute and chronic Urticaria are not emergencies but anaphylaxis and angioedma are emergencies, and are the number one killer.  Drug eruption: Steven Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) - the severe form-, Treat the patient in burn unit.  Bacterial Infections like necrotizing fasciitis: In diabetic patient who develop DKA, or surgical patient, the causative agents are streptococcus or anaerobes or polymythrobs mixed. It needs an early diagnosis because it can be fatal within hours. It goes to the fascia, subcutaneous tissue, muscle and skin. Patient presents as dusky red visculation erythema, comes from entry of surgical site, it’ll progress to blisters, then thrombosis of vessels, and disruption due to bacteria epically in ketoacidosis. Treatment is by surgical intervention and antibiotic. It eats the skin and the muscle.)  Fungal infections e.g. Mucromycosis occur in DKA or immunocompromised patients “saprophytic organism” i.e. found normally in food environment need acidic media and glucose to grow. Patient presents as dusky red erythema with gangrene on face, paranasal sinuses, around eyes, nose. Both organisms are killers and need surgical Treatment. (Mucormycosis refers to several different diseases caused by infection with fungi in the order of Mucorales fungi).  Varicella Zoster.  Congenital Candida.  Meningiotoximia in patient with meningitis, lead to necrosis of the skin.  SSS: Staphylococcal Scaled Skin Syndrome due to exotoxin, in children less than 6 years, resembles TEN the skin is denuded.  Autoimmune blistering disease: not all of them are emergencies but: o Bullous Pemphigoid is an emergency, steroid is life saving also, and it appears like TEN. o Pemphigus Vulgaris: look like TEN, will cause sloughing of skin as if the epidermis wasn’t there (can’t keep fluid in and gets bacteria out) lead to infection, as burn patients.

1 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Causes of blister: burn, cold, trauma, insect, drugs.  Cellulites: common, caused by streptococcus or staphylococcus aureus or others. Always look between small toes “portal of entry “. Treatment IV antibiotic, must be early or the patient will go into bacteremia.  Erysipelas: Treatment IV antibiotic for better absorption, must be early or the patient will go into bacteremia. Ideal situation admit the patient, if it was mild only P.O. antibiotic.  Pediatric emergency: o Herpes simplex in neonate can be fatal because of organ involvement e.g. Encephalitis. o Candida in young children. o Hemangioma “tumor “on the face. o Kawasaki infection. Patient presents as reactive erythema, clinical dignosis, pick up the patient as soon as possible then treatment or it will lead to coronary artery thrombosis, common in children < 5 years old with high mortality rate.  Skin failure is the end result of dermatological emergencies.

We will talk about some of the emergency cases in details.

URTICARIA AND ANGIOEDMA: Urticaria: inflammatory reaction in the skin, causing leakage of capillaries in the dermis. Angioedema: Involving oedema of the deep dermis or subcutaneous and submucosal areas.

Essentials of Diagnosis:-  Wheals or hives. (Circumscribed plaque, annular or circular, small or large can reach 20cm in diameter. Pain and itching are subjective. Wheal shortly lived for 24 hrs, lesion comes and goes, takes few hours to minutes to disappear.)  Evanescent: individual wheals disappear within 24 hours and often within minutes.  Urticated lesion: look like urticaria, but it may persist for more than 24 hrs, e.g. bullous pemohigoid.  Changing of configuration, it can be small size 4-5 cm and can lead to 20 cm.

What is the major mediator of Urticaria? Histamine. Other mediators secreted by mast cells: leukotrines, prostaglandins, substance B, bradykinin. Can be direct or indirect.

Pathogenic mechanism:  Immunologic Type I (IgE mediated) is anaphylaxis; we test it by skin prick test.  Type III: Immune complex mediated, mainly urticarial vasculitis: destruction and inflammation of blood vessel, the lesion (wheal) stays more than 24hrs, painful

2 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani burning ecchymosis more than itching. You have to exclude major organ involvement in vasculitis; GIT, renal and if it was involved start systemic steroids, otherwise if it was a skin involvement only we don’t start systemic steroids. Causes might be drug reaction “common cause “, Infection, connective tissue disease, neoplasia. Other examples of Immune complex reaction are: nephritis in SLE, classical e.g. is Serum Sickness reaction always with arthritis.  Non immunologic: activation of the alternative complements pathway and direct release of histamine. From basophiles or tissue mast cells by drugs or chemicals. (We don’t need IgE) classical example is drug like vancomycin, radio contrast media, Opioids, we call it anaphylactoid reaction.  Pencil eraser urticaria: very small classical presentation of cholinergic urticaria is a subcategory of physical urticaria.  Angioedema usually in the soft tissue like eyelids, lips mucosa and scrotum, palms and soles. It is a local anaphylaxis in the skin.

Classification of Hypersensitivity Reactions: Hypersensitivity is a state in which the immune responses frequently take place in such a way that cell damage occurs and harmful pathological lesions may occur.

5 types of hypersensitivity are recognized:

Type I (Anaphylaxis): Immediate (Antibody mediated):  It is IgE-mediated. An antigen (allergen) reacting with specifically sensitized IgE that is fixed to mast cells, through its FC portion → Degranulation of mast cells release of their mediators e.g. Histamine, leukotrienes, Eosinophil Chemotactic Factor and Neutrophil Chemotactic Factor.  The offending antigen is identified by intradermal prick tests giving immediate wheal and erythematic reactions or by provocation testing.  There is a strong familial predisposition and a tendency to produce high levels of IgE. e.g. anaphylaxis, urticaria, atopy

3 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Two molecules of IgE antibodies attach to the surface of the mast cell or basophile and Ag is attached to these two molecules.

Type III: Immune-Complex Reactions (arthus phenomenon):  The antigen reacts with specific circulating antibodies → antigen-antibody complexes that act through: o Complement activation and PMNL attraction → inflammatory response. o Platelet aggregation → microthrombi and vasoactive amine release. E.g. serum sickness, nephritis in SLE, Allergic vasculitis, urticarial vasculitis, ? Bullous pemphigoid.

Acute Urticaria: persisting less than 3 months. Others say until 6 weeks. Chronic Urticaria: persisting 3 months or longer.

Urticaria may accompany systemic anaphylaxis or serum sickness reaction.

Serum sickness:  It happens 5 days to 3weeks after initial exposure (type III) immune complex mediated reaction.  Large amount of Ag –Ab complex are deposited in the blood vessels causing vasculitis, classical example are drugs (most common), horse serum, snake serum. 24 ????  Patient presents with: Fever, Urticaria, Angioedema, Joint pain and swelling, lymphadenopathy, occasionally: nephritis or endocarditis with eosinophilia according to the site of vasculitis.  To differentiate between it and the mild form by arthritis.  Minor form of Serum sickness: fever, Urticaria, transitory joint tenderness. Without organ involvement.

Causes of Urticaria and Angioedema:  Drugs: Animal sera, vaccines containing egg protein (measles, mumps, rubella), desensitizing agents, Antibiotics, ACEI (captopril, -pril), radio-contrast media, cylogenase inhibitors (.asp, NSAID)  Foods. E.g. strawberry, egg, fish.  Physical causes, dermatographism.  Inhalants.  Hereditary causes, hereditary Angioedema.  Infections hep B, hep C, rubella, viral.  Vasculitis.  Insect bites acute.

4 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Autoimmune disease esp. SLE usually chronic.  Thyroid autoimmune disease.  Contactants.  Idiopathic.  Parasitic infestation.

Desensitizing agents: we give the Ag in small amount and the patient will produce Ab and he will be immune, this procedure can be serious, so, u need to do it in specialized center.

Drug, food, infections are the most common causes of acute urticaria.

Chronic urticaria:  Commonest cause of chronic urticaria is idiopathic 90%, it is difficult to know the source of the Ag, it can be anywhere; 31cotton, Aspergillus.  The clearest thing in chronic urticaria is autoimmune and physical e.g. cholinergic urticaria: pen-point urticated wheal, pencil eraser sign (papule with flare of erythema) due to increase body temperature (hot shower, exercise) pruritic, pin prick sensation, usually they don’t respond to non sedative antihistamines. It doesn’t need investigation because it is clear.  The most common type of cholinergic urticaria is dermatographism: stroking the skin will cause elevation due to axon irritation. 5% of normal people can have dermatographism.  Another type of physical urticaria: o Cold urticaria: at the time of re-warming he develops urticaria due to vasoconstriction. These patients have the risk of drowning if they swim in cold water. o Solar urticaria due to sun exposure o Vibratory urticaria. o Pressure urticaria when the patient sleeps on his back, he wakes up with urtiacaria.

Hereditary Angioedema:  Autosomal dominant.  It can present with Angioedema without urtiacaria.  It is usually painful more than pruritic.  Associated with systemic symptoms: mainly gastric e.g. intussuption, edema and abdominal pain.

5 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 C1 esterase deficiency cause the release of complement C4 C2  The risk of this entity that it is nonresponsive to the usual therapy of urticaria (antihistamine, systemic steroid) they respond to antiandrogen drugs like Danazol, we give it to raise C1 esterase level, it is given as prophylaxis but it take time e.g. if the patient is going to do surgery or tooth extraction or any stress. If major surgery, we give fresh frozen plasma.

Vasculitis:  Causes: AI disease, drug.  How urticaria with vasculitis present?  The lesion is urticated i.e. the single lesion persist for more than 24 hour.  It is painful more than pruritic  vasculitis is pathological diagnosis i.e. you need to take biopsy: extravasations of RBC. We can use immunofluresence.  The most imp organ u are consired about is the kidney. So we need urine analysis.

Approach to the patient with chronic Urticaria:

History: Acute or chronic. Systemic symptoms (headach, fever, abdominal, arthritis) Drug (OTC).

Examine The lymph node. The patient may have occult malignancy, look for organomegaly.

Investigation:  CBC: elevated ESR, elevated eosinophils.  Hep. B, Hep. C.  Thyroid function.  ANA.  Prick test.  Urine for culture, stool for parasite.  If the pt have symptoms of lymphoma: loss of weight, loss of appetite, night sweating we will do chest Xray or CT scan.  If the patient has history of cervical cancer, do colposcopy.  If there is increase in ESR, do peripheral bloods smear.

Treatment:  Elimination or avoidance of the causative agent.  Non-sedating H1 antagonists (main treatment in chronic urticaria). one or combination.  Sedating H1 antagonists

6 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Corticosteroids  H2 antagonists  Doxpein  Leukotriene Antagonists  Cyclosporin  I.V. immunoglobulins

 The main mediator in urticaria is histamine, so we need antihistamine to treat it. But in atopy for example, we don’t give antihistamine unless as placebo.  We don’t give the pt topical antihistamine because it is a great sanitizer i.e. the patient can have contact dermatitis, and if we give the patient systemic antihistamine after the topical one, he may have severe reaction.  Examples of the sedative antihistamine: diphenhydramine, hydroxyzine (Atarax:) potent, useful in cholinergic urticaria.  cyproheptadine (Periactin) useful in cold urticaria.

In acute emergency episodes:  Secure the airway if the pt has angioedema.  I.V. line.  Adrenaline subcutaneous or I.M., repeated every 10 min. The drug of choice if the patient has angioedema with stidor.  Diphenhydramine I.M. or I.V.  Hydrcortisone I.V., to prevent the recurrent.  Patients with severe angioedema should be admitted for at least 24 hours observation particularly where laryngeal edema has occurred.

ANAPHYLAXIS: Essentials of Diagnosis:  Laryngeal edema or bronchospasm or both. (Common cause of mortality related to respiratory system).  Erythema, puritus, urticaria or Angioedma (any or all).  Vomiting, cramps, diarrhea.  Hypotension, cardiac arrhythmia or shocks.

General considerations:  Most killers in medicine.  Within seconds, minutes to hours, severe may be fatal.  IgE mediated. (Type I)  Chemical mediators are released.  Anaphylactoid reactions: clinically similar reactions that involve the nonimmunologic (non antigen-antibody) release of similar mediators e.g. (reactions to radiographic contrast media, aspirin, local anesthetics, morphin.)

7 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani Causative agents:  Drugs (most common drug; Penicillin)  Foods.  Vaccines and Antisera.  Insects – bees, wasps.  Immunotherapy of allergic rhinitis, asthma or stinging insect sensitivity. (denensitization)  Other cases: o Iodinated contrast media, aspirin, and local anesthetics – anaphylactoid reactions. o Treatment of anaphylaxis Sometimes, we need a small amount of the Ag to have anaphylaxis e.g. penicillin in milk, and sometimes, we need large amount e.g. eating a lot of strawberry.

ERYTHRODERMA and EXFOLIATIVE DERMATITIS:

Erythroderma in Uinted Kingdom, Exfoliative Drmatitis in United States, both are the same but different in terms.

Definition: erythema all over the skin > 90% of body surface area with or without scales.

Clinical picture:  Erythema all over the skin > 90% of body surface area with or without scales.  Febrile, Shivering.  Hypothermia or hyperthermia (Hypothermia is more serious then hyperthermia).  Fluid and electrolyte loss.  Hypoprotenemia.

 It is more serious in the extreme of age

Complications:  Hypothermia (patient can’t fix their body temperature. They adjust it according to the outside temperature, so warm the patient and room to 34 degree)  Hyperthermia.  Fluid and electrolyte loss.

8 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Infection.  Heart Failure from increase in hemodynamic circulation.  Stress Induced GIT ulcer.  malabsorption.  Venous thrombosis from dehydration and long stay in bed.  Hypoproteinemia  Anaemia.

Causes: What ever the cause the shape is same  Psoriasis with systemic steroids and coetaneous T-cell lymphoma. (the comments causes).  Mycosis Fungoidis, Sezary Syndrome same as mycosis fungoidis but in blood with sezary cells taken from peripheral blood smear.  Sever atopic dermatitis, seborrheic dermatitis.  Sin infection e.g. PRP “ pytriasis rupus pilaris”  Drug Etiology: Sulphonamides, antimalarias, penicillin, phenytoin, all anti-epilyptics.

Investigation:  CBC, for infection.  U/E (urea and electrolyte) (signs of dehydration or hypoproteinemia.)  ESR.  Skin biopsy and Serial skin biopsy.

Management:  Form history u can differentiate between the causes.  Admission.  Adjust temperature as room temperature.  Check V/S hourly.  Examine lymph nodes, for signs of any neoplasia.  Abdominal examination.  Role out infection  IV hydration and electrolytes and input/output chart.

Treatment:  Treat underlying cause.  Conservative are for infection. You don’t give anaphylactic antibiotic.  Bath i.e. emersion for 15-20 minute then.  Emollients e.g. vasaline for 4 times/day.  High protein diet.

9 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani Extra Notes from 426:  Difference: Surface area, homodynamic circulation  Inflammatory skin disorder like Erythrodermic Psoriasis may be de novo. Patient can  Present with scaling erythroderma all over the body then he is psoriasis no clue for psoriasis here unless patient has previous history of psoriasis so, here your only clue is the history.  Diagnosis is difficult: o May be lymphoma, which is common in KSA o Severe atopic dermatitis o Seborrheic dermatitis o Papulosquamous dx. o Sarcoidosis o Cutaneous T cell lymphoma (very common here) can be in different shape and he should have serial biopsy = Mycosis fungois (not fungal). o When come in blood sezary syndrome. Do Lymph node biopsy o Drug is very famous to cause erythroderma (bad drugs: antimalaria, Anticonvulsant: Phenobarbitone, carpamazepine, tegretol, phenytoin, sulphinomide, penicillin, NSAID o Rare causes Augmentin may cause it also but not usual (patient develop TEN)  Admission and supportive care  Sometimes there is clue, Prp, May be Salmon appearance skin  The only clue is the histo (do biopsy serially) drug is more common than psoriasis.

ERYTHEMA MULTIFORME MAJOR, SJS, TEN: May represent variants of the same disease process. Clinically: Mucous membrane erosions, target lesions epidermal necrosis with skin detachment.

Notes: (The severest reaction is TEN and the milder is erythema multiformi minor as erythema multiformi minor is few skin lesions, papules, target lesions and mucosal membrane involvement. It is mild and won’t affect the patient’s life.)

 Erythema multiformi major same as SJS with 2 or > mucous membrane involvement.  Eryhthema multiformi minor as SJS with one erosion vascular urticated eruption.

SJS (Steven-Johnson Syndrome):  Excellent prognosis.  Two or more sever mucous membrane involvement e.g. oral and genital mucous membrane.  Bad skin involvement = SJS (severe mucous membrane involvement: eye, mouth, internal mm esophagus, rectum, vagina any mm except if the cause is not drug)

10 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 The usual cause of SJS is drugs ( takes 6-8wks to appear ) → typical presentation of SJS.  If the presentation is not typical e.g. mild not severe mucous membrane lesion, think about things that are rare to cause SJS e.g. SLE.

TEN (Toxic Epidermal Necrolysis):  Sever with fatal prognosis.  Skin should be involved more than mucosa; skin appears like burn, more than 30% of surface area.  Should be admitted in burn unit.  most common cause are drugs.  Clinical Features: o Mucosal erosion o Target lesion (nice to see it but not essential) we can see it at other diagnosis multiformi, . SJS. . Skin detachment. . Epidermal necrosis.

Suspected etiologic factors:  Infections  Drugs – anticonvulsants, sulphonamides, allopurinol, NSAI.  Neoplasia  Collagen disease

SJS TEN Pathology: Mucous membrane Skin more involved, involvement and less skin. detached like burns. Prognosis Excellent Fatal

Notes On Suspected Etiological Factors:  Usually Drugs, drugs & drugs (anticonvulsant, sulphonamide, NSAID and  alloperidone which used in gout. The severe the reaction the more it's due to drugs).  Infection (especially micoplasma pneumonia, in children do chest x-Ray and  screen for micoplasma IgM because one of the famous cause)  Connective tissue dx should have clue in examination.  Causes: Metabolic base trigger immune response.  Prognosis related to extent of skin involvement.  Mortality with 30% sepsis and electrolyte imbalance.  Rechallenge and dechallenge: (is unethical might kill the patient)

11 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

o Rechallenge: (when u r sure that certain drug is the cause we give this drug again and see the reaction. It is minor. It includes: 1st commonest morbiliform drug reaction = Maculopapular mild form of drugs reaction, 2nd commonest urticaria may be fatal, give the pt the medication)

 Target lesion (erythema + skin color + sometime necrosis) 3 colors.  It is in erythema multiformi minor due to recurrent herpes simplex

 Erosion in oral mucosa SJS; it can affect any mucosa but the usual one is oral, it can laryngeal, esophageal, conjunctiva.

 Papular reaction in SJS.  Generalized erythema  It starting skin detachment

 SJS.  Eye lesions: permanant eyes lesion.

12 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Buccal mucosa and Nasal mucosa envolved.  Nikolosky sign.

Generalized skin TEN erythematous if the 30% of skin is popular eruption involved→TEN if around raw skin. less→SJS but this is In red spot Skin not a rule. starts erosion , In TEN skin is tender within 1-2 day Palm is 1% all skin will detach.

Nickolesky sign Defuse In: TEN, SSS erythema (Scalded skin syndrome) , Sever eyes and lips Pemphigus affection Vulgaris. TEN

Pathogenesis: Metabolic base may trigger an immune response

Prognosis:  Related to extent of skin involvement.  Mortality for TEN: 30% and it rises up to 60% with addition of steroids. Related to sepsis, fluid and electrolyte imbalance.

Management  Early diagnosis, withdrawal of suspected drug (Don't give prophylaxis antibiotic).  Patient best cared in a burn or I.C.U.  Input and output chart.  You don't give unnecessary medication because if he had a drug reaction he may have another one.  Replacement of I.V. fluids and electrolytes.

13 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 High calorie diet as burn patients.  Systemic corticosteroids are controversial.  Acetyl seste given IV for TEN (controversial).  Best treatment is supportive.  Care for mucous membrane; refer to ophthalmologist for eye involvement.  Diagnose and treat complicating infections. 

ExtraPrevention Notes from. 426:  No systemic steroid (controversial) (increase mortality and prone to sepsis, but if u give it, give it early within 3-4 days) in our school don't give it  Some medication have some help Immunoglobulin and Acetyl sestet  Acetyl seste to counter panadol overdose  You don't give flamazine as in burn, no, give Vaseline?  In general stop the causative medication and treat early.

KAWASAKI SYNDROME:

 More common in children but would be seen in adults.  Cause not known yet but it might be reactive to viral or bacterial infection.  Typical Criteria: Fever > 5 days “major or essential” with the following : o Conjunctival injection. o Strawberry like tongue with chelitis. o Disquamation or pealing around the fingers “peri-angual” important sign. o Non-specific rash e.g. peri-anal area buttocks. o Cervical lymphdenopathy  Sx : very important To prevent Cardiac involvement “ Coronary artery thrombosis aneurysm “

14 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Investigation: o CBC. o ESR “thrombocytosis increased platelets“. o Serial ECG to detect coronary artery stenosis or aneurysm.  Treatment: both are very crucial o Aspirin in acute cases >>> high dose, chronic cases>> low dose 4-5mg/kg. st o Immunoglobulins in acute cases only for 1 5 days either small dose or 1 dose over 12 hrs.

Kawasaki syndrome. Nonopurulent conjuctival injection and “cherry red” lips with fissuring and crusting are early signs of the disease.

15 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani The hands become red and swollen.

The hands peel approximately 2 weeks after the onset of fever.

16 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

DRUG ERUPTION: (not in 426 notes)

Most important: TEN, Erythroderma.

Definition: any reaction that results from drugs used for treatment or investigation. Incidence: Varies (10% - 20% - 30%) Out patient, in patient, ICU.

 More in females, elderly and AIDs patient, because they lack glutathione, which is anti-oxidant that scavenge (i.e. eat it or engulf it) toxic metabolites “responsible for such toxic reaction”, Prone for sever TEN especially who are taking septrin “sulfamethaxazone”.  Less in children  Sjogren Syndrome more prone than Rhematoid Arthritis or SLE due to Disturbance in leukocyte function.  Route of administration: IM > IV > PO least sensitization.

Important clinical notes:  Topical anti-histamine (sensitizer) doctors not allowed to give it, because some patient got sensitize from it, and if he got sensitized from topical he will develop cross-reaction against P.O. then it will lead to sever eczematous drug reaction.

Approch:  Clinical diagnosis is very important.  Draw a chart for analysis, especially in sick or immuno-compromised patient. (know when it happen, duration, association with the usage of the drug-rash)  Differential diagnosis e.g. viral exanthema, drug reaction. Patient present with morbilliform of exanthematous reaction.  Confirmation: if patient got mild morbilliform or simple drug reaction do rechallenge i.e. when you stop the drug the rash will subside.  Research, it is very important to know about each drug’s side effect, e.g. In blistering disease which drug could cause it or aggravate it.

Most common types: A. Coetaneous: 1. Exanthematous (erythema) or morbilifrom: 90% simple maculopapular 2. Urticaria: Fixed drug eruption, angioedema, serum sickness (anuler erythema i.e. center free periphery… sage like rash erthematous) 3. Hypersensitivity syndrome: peculiar, triad:  Fever.  Skin eruption.  Internal organ involvement mainly liver infection “hepatitis”, could be life threatening if the patient continues on the same

17 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani drug and didn’t stop it, which will lead to lymphoma, from first exposure.  Diagnosed clinically: o Maculopapular → pustular → polymorph skin eruption or ↑LFT estrase, CBC ↑ esinophills. o Examine lymph nodes for lymphadenopathy.  Causes: o Anti-convulsant, mostly phenytoin, phenobarbitone, carbamezapine, sulfonamide, dapsone, allopurirol, azathioprine, minocycline. o Na-valporate: no cross reaction with other anticonvulsant. Safest. o Lamotrigine: no cross reaction with other anticonvulsant, but could cause HSR. o Other organs could be involved; renal, pneumonitis.  Treatment: Stop the medication, stop systemic steroids. 4. Latex allergy: Natural rubber protein → Typical reaction e.g.) contact dermatitis → fetal anaphylaxis) or even from smelling the powder, patients prone to it are; spina bifida patient, patient frequent gloved examination, IV, cath.  Food cross reaction with latex protein e.g. Banana, kiwi, avocado, chestnuts. 5. Anaphylaxis and anaphylactoid reaction: most killers. 6. Erythema multifomi (target lesion), SJS (spotting of tongue involvement of palate, eye, skin involvement and erosion.) 7. TEN: Detachment of the skin (dermis completely). Treatment is to stop medication e.g. from treatment itself if it happens in a child. Differential diagnosis are bacterial infection due to toxic secreted form the bacteria “Staphylococcal Scalded Skin Syndrome” (no mucous membrance subcorneal split in skin, very high in stratum corneum, could be form nursery or carrers in their nose, hands, phage( it means from which strain or kind is it ? it is phage 2) 8. Erythroderma. 9. Most typical drug reaction is fixed drug eruption that looks like other with using the same drug, same rash, same site, every time with involvement of mucous membrane or with out.  Brownish pigmentation with defined patch (round).  Erythema in center filled with fluid → blister (single or multiple).  Ruptured blister of fixed drug eruption, typical presentation is erythema on hands, lister on glands penis.  E.g. tetracycline, anti-inflammatory, minocin AKA minocycline, septrin.

18 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani 10. Lichenoid eruption: wide spread, no oral muscous membreane involvement to differentiate from LP, drugs that could cause LP gold (β- blockers) psoriasiform reaction.  Exacerbation of psoriasis drugs e.g. Lithium, β-blocker, anti- malarial. 11. Photosensitivity:  Caused by: psoralen tablets, doxycycline and other tetracyclines, demochlorecycline.  It could be either: o Allergic: eczema, or as in patch test scattered. o Toxic: as sunburn. Eye, submental areas are clear.  Sub-acute lupus e.g. Hydrochlorethiazide. 12. Grey pigmentation: Drugs that cause it are; minocycline in site of acne scar (pigmentary abnormalities), anti-malarial. 13. Acneform, pustular eruption → drugs e.g. Steroids in form of monomorphic no comedones (same shape). 14. Acute Generalized ecxematous pustulosis (AGEP) i.e. pustular eruption with exanthema with β-lactam antibiotic or other drugs. DDx; pustular psoriasis. 15. Bullous eruption:  Causes: Fixed drug eruption, erythema multiformi (even minor), and drug induced vasculitis. In all these cases patient will present with blister, bullous component.  Drug induced TEN (wide spread blistering):  induced porphyria : abnormal porphyrin.  Pseudoporphyria i.e. abnormal synthesis of heme pathway.  Drug induced Pseudoporphyria: patient got normal level of porphyrin in urine and blood, clinically it has a certain picture especially patient on dialysis or furosemide medication. They present with hand with tense blister, crustation, scarring, millia, common site tense subdermal. o Types: . Drug induced bulllous pemphigoid with erythema and blister, IF linear IgF C3 of bullous pemphogoid . Drug induced pemphigus “thio- medication” causing wide spread pemphigous, blister is intra derml (Dx flaccid) “Inside epidermis” basement membrane intact. More superficial blister more denuded.

19 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

 Exception; TEN deep blisters with denuetion, Trichophyrom rubrum tense blister epidermal (inflammatory fungal infection) with thick keratin in hands and feet. 16. Vasculitis: wide spread with purpura with necrosis.  Cause: Drugs or autoimmune disease, important to rule out organ involvement like kidney and GIT.  IF around blood vessels. i.e. deposition in immunofluresence test will be found around blood vessel. 17. Pitryasis rosea like eruption by gold compounds. 18. Erythema nodosum form of panniculitis i.e. inflammation of fat, nodules in chin as reaction pattern from drugs or infection e.g. streptococcal, IBD, lymphoma, PD, most common OCP, subcutaneous painful deep seated nodules when it subsides leave color changes on skin (reactive process → inflammation around fat lobule or septa.

 Drug induced lupus with more serology ANA, less other organ involvement e.g. minocene, anti-androgen as spironolactone. . Important to take family history and if the patient was positive to lupus they are prone to have drug induced lupus.  Relative contraindication to give Minocin; got lots of side effects e.g. pneumonitis, Hypersensitivity syndrome reaction, lupus like reaction, not used with patient having acne scar pigmentation. Although it is best systemic antibiotic used in least resistant types and more effective “sensitive i.e. killing” against propionic bacteria causing acne, do serial LFT when you use it.  Doxycycline 1st line antibiotic, not the best but yet safer than Minocin.  Acne of pregnancy, use Azithromycin, long half life 3-4 days, better choice.  Erythromycin cause gastric upset that’s why not used anymore.

VESICULOBULLOUS DISORDERS (Blistering disorders): Definition: Circumscribed skin lesions containing fluid ≤ 5mm: vesicle >5mm:- bulla

Which skiing findings are helpful in evaluating a patient with blister? • Distribution: Generalized skin and oral cavity (mucosa) as in pemphigus, it may start early before any skin involvement few months up to one year before diagnosis. Patient presents with erosions picked up first by dentist. • Symmetry: Arrangement: a) grouped. b) Linear. • Associated lesions: Bullous impetigo. Patient presents with urtication for 1 year, Pemphigoid Gestatiolis “or herpes gestatiolis”

20 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani with pregnancy with urtication. • Additional types of skin lesions –urtic. • Characteristic of blisters: Important. • Intra dermal “inside dermis” as Pemphigus Vulgaris superficial flaccid thin fragile. • Deep tense blister in Bullous Impetigo below dermis “sub-epidermal”.

Which test are most useful in evaluating Vesiculobullous Disorders? • Cultures (Bact, viruses, and fungi) take weeks. • Smears from blisters (Bact, dermatophytes, and multinucleate giant cells of H.S) quicker than culture. • Skin biopsy – non infectious cause autoimmune disease as PV, BI do fresh IF important, deposition of immunoglobulins. Notes: • Bacterial culture in New born blister in napkin area, Grouped vesicles → viral infection. Vesicles in sole or hands → fungal infection “trichophyton rubrum “Deep blister. • Indirect IF is done from pt serum to see disease activity (Treatment < tapering dose).

When are special tests necessary to diagnose blistering disorders of the skin? All depend on patient clinical manifestation: • Routine Hist. A must. • Dif- immunobullous Dis./IIF • EM – EB. • Urine porphyrin- PCT (if patient got dark urine, photosensitivity, do it) • Zinc levels – ADE . (Zinc is deficient in neonates from mouth, genital area the blisters will be around them.)

Pemphigus: Essential of dignosis: • Flaccid blisters, weeping painful erosions. • Mucous membrane involvement (starting point). • Nikolosky’s sign (i.e. rubburing of skin lead to detachment) • Asboe – Hansen sign or (bulla spread sign) i.e. when you press on a blister will spread to normal skin. • Acantholysis and intra epidermal cleft. • IgG, C3 in intercellular space of epid. • IF: - S.Abs to epidermal cell surface Ags – Titer reflects Dis. Activity. • Rare, Lethal, autoimmune blistering disorder, life threatening, leads to sloughing of skin as burn patient. • Age – sixth decade • Common in Jews, South KSA. • Once diagnosed, treatment is by steroids quickly.

21 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

Mild erosion. Diagnosed Pemphigus Vulgaris. White by skin biopsy, IF is a must, sloughing with severe treat patient or else will crustation. Treat quickly develop into severe type of seriously aggressively. pemphigus “Pemphigus Vulgaris”

“Folecious type of pemphigus” superficial in subcorneal area, less blistering, more scales.

Pemphigus Vulgaris flaccid thin bulla in inner thigh

Pemphigus Vulgaris Nail changes exophytic, detachment of nail shed out, paronychia

22 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

Direct IF.

Indirect IF from blood Serum

• Skin biopsy – light Mic. • IF: IgG, C3 in intercellular substance of epid. • IF: levels reflect the activity of Dis.

Treatment for life: • Dressing like burn patient, care for infection. • Corticosteroids. • Immunosuppressive therapy: 1) Azathioprine old one, benign, side effects on liver. 2) mycophenolate benign expensive used with renal transplant patient, side effect; bone marrow suppression. 3) mofetil. • IVIG in resistant cases • Anti CD-20, Rituximab IV some researches says it cause remission. Steroids and immuno-suppressants, treatment for life on low dose.

Pemphigoid Group of disorders: Bullous pemphigoid, herpes gestations, cicatricial pemphigoid (affect mucous membrane of eye causing blindness: auto immune sub epidermal blistering disorder. With circulating IgG and BMZ- bound IgG ABS α C3)

Bullous Pemphigoid: Benign. Patient presents with urtication for 1 yr before appearing of any musous membrane involvement.

23 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani Essentials of Diagnosis: • Large bullae on erythematous plaques or normal appearing skin. • No or only mild involvement of musous membrane. • Sub epidermal blister (could be hemorrhagic). • IgG, C3 at dermal epidermal junction. • ABS. against BMZ in patient’s sera. • Bullous Pemphigoid IgG level is high. • Gestatiolis pemphigoid or herpes gestatiolis ”HG” C3 level is high

Severe excoriation and crustation after rupture of blister. Tense blister erythema, palqeu, Annular urtication, Very typical, acral distribution erosion of skin. in BP, tense blister, crustation after rupture, esoniphills in upper dermis.

Age: Elderly. • Relatively Benign

Clinical Manifestation: • Loc Erythema, Urticaria, Pruritus. • Tense blisters, lower part of abdomin, groin, flexors of Arms and Legs. • Negative Nikolsky’s sign • Course: Variable, untreated B.P. Localized,Spont. Remission, generalized.

24 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani Diagnosis: • CBC: Eosinophilia - 50% IgE: - 70% HIST. DIF → sub- epidermal split. IIF.

Treatment: • Dressing. • Topical antibiotic. • Systemic: Steroid (potent with moderate dose) • Antibiotics: Tetracycline, Minocin. • Dapsone. • Immuno Suppressive: Azathioprine, Mycophenolate, Mofetil. • In all Blistering Disease treatment is compressor, Anti-septic, Topical antibiotic, prevent infection.

Pemphigoid Gestationis: • Erythematous urticarial Plaques, alone or with papules, vesicles blisters, erosions, most on abdomen, proximal extr. • Intense pruritus. • Starts with pregnancy, with the next pregnancy it will start earlier. Because the mothers are using steroids in Neonates investigate for adrenal hypoplasia ”suppression”. • Tense sub epidermal blister. • C3, IgG at BMZ linear arrangement in IF, H.G. Factor in Patient’s Sera 2nd, 3rd Trimester, Flares at post partum, OCP Treatment: 1) Drying agent>> topical Abx , anti-septic Targetoid lesion in 2) Systemic anti-histamine bcz it is very itchy safest in pregnancy e.g. abdomen, Multiple urtication , crustation with chlorphenaramine . small vesicles , in the hand 3) Systemic steroids tense blister.

25 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani

Dermatitis Herpetiformis: • Severe pruritis vesicles. • Associated with gluten sensitive enteropathy. • Pruritic tense blisters on extensors (elbow, knee, upper or lower back, shoulders). • Excoriation so pt. may present with no vesicles.

Phatology: • Sub epidermal blister, prominent neutrophil infiltration. • Dif: granular IgA very important. Diagnostic in dermal papillae.

26 Dermatologic Emergencies, Drug Eruption, Blistering disorders 426 C1 + 428 C2 Notes Dr. Mona Al-Halawani Associated with gluten sensitive enteropathy similar to celiac disease Treatment: • No steroids. • Gluten free diet. • Dapsone – 1st line of treatment (before starting check G6PD because one of its side effects is hemolysis, if patient can’t tolerate it go for Sulfa pyridine) • Others: Tetracycline and Nicotinamide, or Minocin (for Mild disease, safer).

GOOD LUCK.. Done by: Maha Alyousef and Hala Alrugaib Edited by: Hala Alrugaib