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Erythema and Urticaria

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1 Erythema and Urticaria
August 12, 2003

2 Flushing Transient diffuse redness of face & neck
Niacin, CCBs, 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 Elevated Estrogen Cirrhosis Liver CA metastatic

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 of eos and neuts

5 Erythema Multiforme Minor
EM due to herpes virus (HAEM) +/- oral. SJS, TEN due to meds, mycoplasma, radiation. 20% of cases cannot be classified. Self-l imited, recurrent, young adults, spring/fall Mild or no prodrome x 1-4 weeks Lesions evolve over 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
Usually associated with orolabial HSV Antivirals improve it and steroids worsen it Appear 1-3 weeks after the herpes lesion Sometimes EMM comes without herpes Sometimes herpes comes without EMM

10 Oral Erythema Multiforme
Oral only in 45%, lip & oral 30% Oral specialists usually handle this Tongue, gingiva and buccal mucosa are the most severly affected. Erosions +/- a 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 EM Treatment Depends on etiology. If HSV: Treat HSV, sunblock.
If SJS or TEN, stop medications such as sulfonamides, antibiotics, NSAIDS, allopurinol, anticonvulsants. Look for history of mycoplasma or radiation therapy. SJS, TEN: Burn unit, IVIG, Steroids etc.

13 Erythema Annulare Centrifugum

14 EAC: “coat in sleeve”

15 Erythema Annulare Centrifugum
Most common gyrate erythema Polycyclic, trailing scale at inner border Eccentric growth 2-3mm per day Asymptomatic but chronic, recurrent Look for tineas, rarely CA Good H&P, CBC, LFT’s, UA and CXR

16 Erythema Gyratum Repens

17 Erythema Gyratum Repens
Rare Undulating bands of slightly elevated wavy erythema over the entire body “Wood grain” with “trailing scale” Severe pruritis, eosinophilia 80% underlying malignancy, MC lung CA Rash may precede CA by 9 months. Remove CA, rash resolves.

18 Annular Erythema of Infancy
Rare Onset: 6 months, resolves by 11 months Lesions are transitory, last hours No treatment necessary

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 Necrolytic Migratory Erythema
Aka Glucagonoma Syndrome Amino Precursor and uptake decarboxylation (APUD) cell tumor of the pancreas Elevated serum Glucagon, low Zinc Pancreas scan may be normal Distribution: 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

22 Erythema Brucellum Veterinarians and Cattlemen
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, this is a sensitization phenomenon.

23 Recurrent Granulomatous Dermatits with Eosinophilia
Aka Eosinophilic Cellulitis, Well’s Synd.

24 Dermal eos and histiocytes surrounding central masses of brightly pink collagen that has lost its fibrillar appearance and is more amporphous “FLAME FIGURES”

25 Well’s Syndrome 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

26 Erythema Nodosum Young adult women
Crops of bilateral deep tender nodules, pretibial Overlying skin shiny, red. Onset acute with arthralgia, malaise, edema 2-3 days lesions flatten and have a bruised appearance, may last days or weeks

27 Erythema Nodosum in Sarcoid
MC nonspecific cutaneous finding in sarcoidosis Young females Anterior shins Good prognosis Lofgren’s Syndrome = fever, arthralgias, hilar adenopathy, fatigue, EN

28 Erythema Nodosum Reactive Process
Strep, Yersinia, Salmonella, Shigella, Coccidiomycosis, Histoplasmosis, Sporotrichosis, Blastomycosis, Toxoplasmosis, TB, Sarcoidosis, Hematologic Malignancies, Pregnancy, Oral contraceptives HISTO: Septal panniculitis

29 Sweet’s Syndrome


31 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 Overlap between sweets and pyoderma gangrenosum well documented.

32 Marshall’s Syndrome Skin lesions that resemble Sweet’s but is followed by Cutis Laxa changes Children Small red papules expand to urticarial targetoid plaques with hypopigmented centers. Eosinophilic infiltrated may be seen Biopsies demonstrate loss of elastin

33 Marked diminution of elastic fibers in lower dermis (Verhoeff-van Gieson stain).

34 Pyoderma Gangrenosum ulcers with distinct rolled edges, sharply marginated, undermined blue to purple borders

35 Pyoderma Gangrenosum Pathergy (Sweet’s too) 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 associated: Leukemia, Myeloma, Polycythemia vera, Hep C, SLE, HIV, pregnancy, Takayasu’s arteritis

36 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 Wegner’s granulomatosis

37 TX: Pyoderma Gangrenosum
Excise colon segment for IBS, UC, Crohns Rule out/treat malignancy or infection Steroids: topical, IL or oral depending on severity and aggressiveness Topical 4% cromolyn or tacrolimus Hyperbaric oxygen- rapid pain relief Cyclosporine, Sulfasalazine, Dapsone, Clofazimine, Azathioprine, Mycophenolate, IVIG, Plasma exchange

38 Urticaria

39 History: Use a questionnaire!
Recent illness (eg, fever, sore throat, cough, rhinorrhea, vomiting, diarrhea, headache) INFECTIOUS: STREP, HEP C, H. PYLORI Medication use (especially 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 (eg, 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

40 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

41 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 Get a good drug history: ACEIs, NSAIDS, Antibiotics

42 H&E: collagen bundles separated by edema, perivascular infiltrate

43 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.

44 Urticaria Evaluation Good H&P is most cost effective
Dental and sinus x rays can be of benefit Order laboratory tests based only on symptoms and signs from H&P including: Thyroid, LFTs, Hepatitis panel, ANA, CBC. Eosinophilia -> search for parasites Food skin tests.

45 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

46 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

47 Anaphylaxis Acute, life threatening urticaria/angioedema 90%, SOB 60%
Onset: peak severity within 5-30 minutes MC causes of serious anaphylactic reactions are: Anitbiotics, especially PCNs, NSAIDS, Radiographic contrast dyes 2nd MC cause – hymenoptera, shellfish

48 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: mL dose of 1:1000 dilution of epinephrine SQ q minutes IV Solumedrol 50mg q6h x 2-4 doses Benadryl, aminophyliine, neb. Metaproterenol, O2, glucagon, intubation, IV fluids.

49 Angioedema

50 Hereditary Angioedema
2nd to 4th decade, + Family history, AD May occur q2 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

51 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 from laryngeal edema Tx of choice: fresh frozen plasma, stanazol, tranexamic acid

52 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 best screening test, it will be low in both of the above cases.

53 HA - Treatment 25% of deaths due to HA are the result of laryngeal edema 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 and useful for acute or chronic HA.

54 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.

55 Schnitzler’s Syndrome
Chronic non-pruritic urticaria Fever of unknown origin Disabling bone pain Hyperostosis Increased SED rate Macroglobulinemia (IgM Kappa) Tx: Oral Steroids

56 Physical Urticarias 20% of all urticarias Dermatographism
Cholinergic/Adrenergic Cold/Heat Solar Pressure Exercise induced Aquagenic Vibratory Angioedema

57 Dermatographism

58 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

59 Cholinergic Urticaria

60 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

61 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

62 Cold Urticaria and Angioedema
MC Face/hands, occurs with rewarming 25% Patients atopic Tx: PERIACTIN 4mg TID Desensitize: repeated colder exposures. Test: Ice cube in saran wrap x 5-20 min. Assoc: Cryoglobulins, Myeloma, Syphillis, Hepatitis, Mononucleosis Familial variant – Bx LCV, Tx Stanazol

63 Heat Urticaria 5 minutes 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.

64 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, Repetetive phototherapy.

65 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

66 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

67 Vibratory Angioedema AD or acquired Usually occupational in origin
Plasma histamine levels elevated during attacks Provocation test: Laboratory vortex vibration applied for 5 minutes Tx: OAH

68 Aquagenic Urticaria Water, seawater, tears, sweat, saliva at any temperature may provoke Immediately or within minutes and clear within seconds. Wheezing, dysphagia, SOB may accompany Water soluble antigens the etiology? Tx: Petrolatum, OAH, PUVA.

69 The End

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