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    Erythema and Urticaria

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    1 : Erythema and Urticaria August 31, 2004
    2 : Flushing Transient, diffuse redness of face/neck/trunk Niacin, Calcium Channel Blockers, cyclosporine, chemotx, vancomycin, bromocriptine, contrast dye, tamoxifen, leuprolide acetate, high dose methylprednisolone Capsaicin (red pepper), sodium nitrate, sulfites, alcohol, food poisoning (ciguatera, scrombroid) Carcinoid, Mastocytosis, Pheochromocytoma Menopause, oophorectomy
    3 : Erythema Palmare Hypothenar erythema Elevated Estrogen Cirrhosis Metastatic Liver CA Pregnancy
    4 : Erythema Toxicum Neonatorum Occurs in most healthy full term newborns, usually on 2nd - 3rd day. Multiple papules that rapidly evolve into pustules with an erythematous base Lesions may become confluent, especially on the face No fever, gone by 10th day DDx: Miliaria, Herpes, Bacterial folliculitis, scabies Pustule smear revealing eosinophils is diagnostic. Bx shows follliculitis with eosinophils and neutrophils
    5 : Erythema Multiforme Minor AKA Herpes Simplex-Associated EM (HAEM) Minor is typically associated with orolabial HSV Major (SJS) is associated with sulfonamides, NSAIDS, antibiotics, allopurinol, Mycoplasma pneumoniae, anticonvulsants, and radiation Cause not identified in 20% of cases Self-limited, recurrent, young adults, spring/fall Mild or no prodrome lasting 1-4 weeks Lesions evolve over 24-48 hours “Target” or “iris” lesions are diagnostic
    6 : Erythema Multiforme
    7 : 1) Central dusky purpuric area 2) Elevated edematous pale ring 3) Surrounding macular erythema
    8 : EM: Vacuolar interface with “tagging” of lymphocytes along DEJ with necrotic and apoptotic keratinocytes Cytoid Bodies
    9 : Erythema Multiforme Minor Locations: dorsal feet, limbs, elbows, knees, palms and soles EMM appears 1-3 weeks after the herpes lesion Tx: Self-limited, supportive care If HSV: antivirals improve/steroid worsen; sunblock If SJS or TEN, stop suspect medications, admit to burn unit, IVIG, steroids, etc.
    10 : Oral Erythema Multiforme Usually limited to orolabial involvement Concomitant skin involvement in 25% Tongue, gingiva and buccal mucosa are the most severly affected Erosions +/- pseudomembrane Important to r/o Candida, because topical antifungal therapy leads to improvement in 40% of cases in which Candida is found, otherwise prednisone
    11 : Oral Erythema Multiforme
    12 : Erythema Annulare Centrifugum Most common gyrate erythema Unknown pathogenesis Polycyclic, trailing scale at inner border Eccentric growth 2-3mm per day Asymptomatic but chronic, recurrent Evaluate for Tinea Recommended: Good H&P, CBC, LFT’s, UA and CXR to r/o internal cancer Responsive to topical steroids
    13 : Erythema Annulare Centrifugum
    14 : EAC: “coat in sleeve” = lymphos tightly associated with vessels
    15 : Erythema Gyratum Repens Rare Undulating bands of slightly elevated wavy erythema over the entire body “Wood grain” with “trailing scale” Severe pruritis; eosinophilia often found 80% underlying malignancy, MC lung CA Rash may precede CA by 9 months Remove CA, rash resolves
    16 : Erythema Gyratum Repens “WOOD GRAIN” APPEARANCE
    17 : Annular Erythema of Infancy Rare Lesions are transitory, last 36-48 hours Onset: 6 months, resolves by 11 months without treatment
    18 : Necrolytic Migratory Erythema AKA Glucagonoma Syndrome Associated with amino precursor and uptake decarboxylation (APUD) tumor of the pancreas Increased glucagon, decreased zinc Pancreas scan may be normal Location: periorificial, flexural, acral Papulovesicular lesions coalesce, form pustules then erode. Active erythematous gyrate or circinate borders with central confluence Patients present ill, with hyperglycemia, weight loss, diarrhea, anemia, atrophic glossitis, angular cheilitis Tx: removal of tumor
    19 : Necrolytic Migratory Erythema
    20 : NME path identical to Zinc Defic. Acanthosis with upper epidermal necrolysis. There is a pallor of the keratinocytes in the granular layer due to intracellular edema, thus “loss” of the granular cell layer. Edema correlates with vesicles.
    21 : Erythema Brucellum Vets and Cow tenders Starts with itching and erythema of the upper extremities, sometimes face and neck, then skin thickens and erupts with conical follicular papules Resolves without Tx in 2 weeks Brucella organisms not identified in lesions, suggesting a sensitization phenomenon
    22 : Recurrent Granulomatous Dermatitis with Eosinophilia Clinical hybrid between cellulitis and urticaria Recurrent Reaction pattern to many possible things, including bites, onchocerciasis, parasites, varicella, mumps, tetanus immunization, drug reactions, myeloproliferative dz, atopic diathesis, hypereosinophilic synd., fungal infection TX: OAH, TCN, UVB, PUVA, Dapsone, Prednisone low dose
    23 : Recurrent Granulomatous Dermatits with Eosinophilia AKA Eosinophilic Cellulitis, Well’s Syndrome
    24 : Dermal eos and histiocytes surrounding central masses of brightly pink collagen that has lost its fibrillar appearance and is more amorphous “FLAME FIGURES”
    25 : Erythema Nodosum Young adult women Crops of bilateral deep tender nodules, pretibial Overlying skin shiny, red Acute onset with arthralgia, malaise, edema In 2-3 days, lesions flatten and have a bruised appearance; may last days or weeks
    26 : Erythema Nodosum in Sarcoid MC nonspecific cutaneous finding in sarcoidosis Young females Anterior shins Good prognosis Lofgren’s Syndrome = EN with fever, arthralgias, hilar adenopathy, & fatigue
    27 : Erythema Nodosum Reactive Process Strep, Yersinia, Salmonella, Shigella, Coccidiomycosis, Histoplasmosis, Sporotrichosis, Blastomycosis, Toxoplasmosis, TB, Sarcoidosis, Hematologic Malignancies, Pregnancy, Oral contraceptives HISTO: Septal panniculitis
    28 : Sweet’s Syndrome
    29 : MAY BURN, BUT DO NOT ITCH PATHERGY
    30 : Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a condition characterized by the sudden onset of fever, leukocytosis, and tender, erythematous, well-demarcated papules and plaques. 71% no known disease 11% hematologic disease (including leukemia) 16% immunologic disease (rheumatoid arthritis, inflammatory bowel disease) 2% pregnancy TX: systemic corticosteroids The overlap between sweets and pyoderma gangrenosum well documented
    31 : Marshall’s Syndrome Skin lesions that resemble Sweet’s but is followed by Cutis Laxa changes Primarily, affects children Small red papules expand to urticarial targetoid plaques with hypopigmented centers Eosinophilic infiltrate may be seen Biopsies demonstrate loss of elastin
    32 : Marked diminution of elastic fibers in lower dermis (Verhoeff-van Gieson stain)
    33 : Pyoderma Gangrenosum Pathergy, as in Sweet’s Syndrome Heal with atrophic scars Extremely painful 50% of pts have associated disease MC: Crohn’s and Ulcerative Colitis 1/3 of PG patients have arthritis Other associations: leukemia, myeloma, polycythemia vera, Hep C, SLE, HIV, pregnancy, Takayasu’s arteritis
    34 : Pyoderma Gangrenosum ulcers with distinct rolled edges, sharply marginated, undermined blue to purple borders
    35 : Pyoderma Gangrenosum Histopathology is not helpful Must rule out deep fungal, mycobacterial, gummatous syphillis, synergistic gangrene, amebiasis Biopsy with special stains and cultures are very important cANCA to rule out Wegener’s granulomatosis
    36 : TX: Pyoderma Gangrenosum Excise colon segment for IBS, UC, Crohn’s Rule out/treat malignancy or infection Steroids: topical, IL or oral depending on severity and aggressiveness Topical 4% cromolyn or tacrolimus Hyperbaric oxygen leads to rapid pain relief Cyclosporine, Sulfasalazine, Dapsone, Clofazimine, Azathioprine, Mycophenolate, IVIG, Plasma exchange
    37 : Urticaria
    38 : History is Key Illness: e.g., fever, sore throat, cough, rhinorrhea, vomiting, diarrhea, headache -- INFECTIOUS: STREP, HEP C, H. PYLORI Medications: ACE inhibitors, which result in angioedema, as well as anesthetics, penicillins, cephalosporins, sulfas, diuretics, aspirin, nonsteroidal anti-inflammatory drugs [NSAIDs], iodides, bromides, quinidine, chloroquine, vancomycin, isoniazid, antiepileptic agents Travel: rule out amebiasis, malaria, helminthics New foods: e.g., shellfish, fish, eggs, cheese, chocolate, nuts, berries, tomatoes, alcohol Perfumes, detergents, lotions, creams, or clothes Exposure to new pets (dander), dust, mold, chemicals, or plants Pregnancy (PUPPP) Contact with nickel (eg, jewelry, jean stud buttons), rubber (eg, gloves, elastic bands), latex, industrial chemicals, and nail polish Sun exposure or cold exposure, exercise
    39 : Urticaria Pathogenesis Increased capillary permeability, which allows proteins and fluids to extravasate Due to histamine release from mast cells degranulating, which in turn recruits eosinophils, neutrophils and basophils Other triggers are leukotrienes (slow reacting substances of anaphylaxis), prostaglandins, proteases, bradykinins
    40 : Chronic Urticaria 1/3 of these patients have circulating functional histamine-releasing autoantibodies that bind to the high-affinity IgE receptor producing mast cell-specific histamine releasing activity Fc epsilon RI
    41 : H&E: collagen bundles separated by edema, perivascular infiltrate
    42 : Urticaria & Angioedema DDx: Clinical diagnosis DDx: Urticarial Vasculitis, Bullous Pemphigoid, GA, Sarcoidosis, CTCL Most of the diseases listed above have lesions that last longer than 24 hours Biopsy urticarial lesions that last > 24 hours
    43 : Urticaria Evaluation Dental and sinus x-rays can be of benefit Order laboratory tests based only on symptoms and signs from H&P including: TSH, LFTs, Hepatitis panel, ANA, CBC Eosinophilia: search for parasites Food skin tests
    44 : Urticaria Treatment Tx: OAH, multiple if necessary Simons et al., randomized, double blind parallel series of 23 “refractory” urticarias found 58% of patients preferred H1 + H2 combinations Atarax + Tagamet much better than Zyrtec and Tagamet Cool bathing Pramoxine, Sarna Oral steroids rarely helpful
    45 : Urticaria Treatment Foods to avoid: Fish and shellfish Pork Garlic, onions Mushrooms Tomatoes, melons, strawberries, citrus fruits, pickles and relishes Nuts, peanuts, cheese Remove suspected food x 3 weeks then resume
    46 : Anaphylaxis Acute, life threatening urticaria/angioedema 90%, SOB 60% Onset: peak severity within 5-30 minutes MC causes of serious anaphylactic reactions are: antibiotics, especially PCNs, NSAIDS, radiographic contrast dyes 2nd MC cause – hymenoptera, shellfish
    47 : Anaphylaxis Mortality rate less than 10% Still account for vast majority of fatal reactions, peak onset 5-30 minutes One of every 2700 hospital patients 500 annual fatalities Tx: 0.3 - 0.5mL dose of 1:1000 dilution of epinephrine SQ q 10-20 minutes IV Solumedrol 50mg q6h x 2-4 doses Benadryl, aminophyliine, neb. metaproterenol, O2, glucagon, intubation, IVFs
    48 : Angioedema
    49 : Hereditary Angioedema 2nd to 4th decade, +Family history, Autosomal Dominant May occur q 2 weeks, lasting 2 to 5 days Eyelid and lip involvement NOT SEEN Face, hands, arms, legs, genitals buttocks, stomach, intestines, bladder affected N/V, colic, may mimic appendicitis Triggers: minor trauma, surgery, sudden changes in temperature or sudden emotional stress Presence of urticaria rules out HA
    50 : Hereditary Angioedema AKA Quincke’s Edema NO PRURITIS OR URTICARIA, +PAIN Low C4, C1, C1q, C2 levels Low or dysfunctional plasma C1 esterase inhibitor protein 25% of deaths are from laryngeal edema Tx of choice: fresh frozen plasma, stanazol, tranexamic acid
    51 : Type I and Type II HA Type I – LOW serum levels of NORMAL C1 esterase inhibitor protein Type II – NORMAL levels of DYSFUNCTIONAL C1 esterase inhibitor protein C4 is best screening test, it will be low in both of the above cases
    52 : HA - Treatment TOC for acute HA is fresh frozen plasma Stanazol useful for short-term prophylaxis in patients undergoing dental surgery, endoscopic surgery or intubation Tranexamic acid in low doses has few side effects -- useful for acute or chronic HA
    53 : Acquired Angioedema Symptoms same as HA, but NO family Hx AKA Caldwell’s Syndrome Occurs at night, pt wakes up with it Acute evanescent circumscribed edema Affects most distensible tissues: eyelids, lips, earlobes, genitalia, mouth, tongue, larynx Swelling is subcutaneous, not dermal Overlying skin is not affected
    54 : Schnitzler’s Syndrome Chronic non-pruritic urticaria Fever of unknown origin Disabling bone pain Hyperostosis Increased ESR Macroglobulinemia (IgM Kappa) Tx: Oral Steroids
    55 : Physical Urticarias 20% of all urticarias Dermatographism Cholinergic/Adrenergic Cold/Heat Solar Pressure Exercise-induced Aquagenic Vibratory angioedema
    56 : Dermatographism
    57 : Dermatographism Sharply localized wheal and flare seconds to minutes after stroking skin 2% to 5% of the population Associated with penicillin induced urticaria, Pepcid (famotidine), hypothyroidism, hyperthyroidism, infectious disease, diabetes mellitus, onset of menopause Tx: OAH
    58 : Cholinergic Urticaria
    59 : Cholinergic Urticaria Acetylcholine induced Tiny punctate extremely pruritic wheals or papules 1-3mm in diameter surrounded by erythema MC trunk and face, spares palms & soles Triggers: exercise, heat Tx: Cold shower, OAH high dose Provoke: Methacholine skin test, heat
    60 : Adrenergic Urticaria Norepinephrine induced Small, 1-5mm papules, +/- pale halo 10-15 minutes after emotional upset, coffee or chocolate Serum adrenalin elevated, histamine NL Tx: Propranolol 10mg QID Provoke: 3 to 10 nanograms noradrenalin intradermally
    61 : Cold Urticaria and Angioedema MC face/hands, occurs with rewarming 25% patients are atopic Tx: PERIACTIN 4mg TID Desensitize: repeated colder exposures Test: Ice cube in saran wrap x 5-20 min. Associations: Cryoglobulins, Myeloma, Syphillis, Hepatitis, Mononucleosis Familial variant – Bx: LCV; Tx: Stanazol
    62 : Heat Urticaria occurs within 5 minutes of exposure Heat > 109.4 farenheit (43 C) Burns, stings, red, swollen, indurated May become generalized with cramps, weakness, flushing, salivation and collapse Tx: heat desensitization Provoke: heated cylinder 122 F x 30 min.
    63 : Solar Urticaria Classified by the wavelength of light causing it Visible light may cause it, so sunscreens may be of little help Sun Avoidance OAH PUVA; repetitive phototherapy
    64 : Pressure Urticaria 3-12 hours after local pressure has been applied MC feet/walking and buttocks/sitting Arthralgias, fever, chills, leukocytosis can occur Tx: ORAL STEROIDS HELPFUL, ANTIHISTAMINES NO HELP! Provoke: 15 lb. weight x 20 minutes
    65 : Exercise Induced Urticaria Not related to body temperature Wheals are larger than those seen in cholinergic urticaria Starts after 5-30 minutes of exercise Patients often atopic Avoid celery and gliadin or other food allergy Tx: OAH
    66 : Vibratory Angioedema Autosomal Dominant or acquired Usually occupational in origin Plasma histamine levels elevated during attacks Provocation test: Laboratory vortex vibration applied for 5 minutes Tx: OAH
    67 : Aquagenic Urticaria Water, seawater, tears, sweat, saliva at any temperature may provoke Immediately or within minutes and clear within 30-60 seconds Wheezing, dysphagia, SOB may accompany Water soluble antigens the etiology? Tx: Petrolatum, OAH, PUVA
    68 : The End
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