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
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 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
“WOOD GRAIN” APPEARANCE

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

30. MAY BURN, BUT DO NOT ITCH
PATHERGY

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