Derm diagnoses you can’t afford to miss

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Applied Evidence

Derm diagnoses you can’t afford to miss

J Fam Pract. 2009 June;58(6):298-306

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References

1. Noe R, Cohen AL, Lederman E, et al. Skin disorders among construction workers following Hurricane Katrina and Hurricane Rita: an outbreak investigation in New Orleans, Louisiana. Arch Dermatol. 2007;143:1393-1398.

2. Kulthanan K, Jiamton S, Thumpimukvatana N, et al. Chronic idiopathic urticaria: prevalence and clinical course. J Dermatol. 2007;34:294-301.

3. Stanway AD, Cohen SN, Chen C, et al. H1-antihistamines for chronic urticaria. Cochrane Database Syst Rev. 2008(2):CD006137.-

4. Grattan CE, Humphreys F. British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Guidelines for evaluation and management of urticaria in adults and children. Br J Dermatol. 2007;157:1116-1123.

5. Kozel MM, Mekkes JR, Bossuyt PM, et al. Natural course of physical and chronic urticaria and angioedema in 220 patients. J Am Acad Dermatol. 2001;45:387-391.

6. Nettis E, Colanardi MC, Soccio AL, et al. Double-blind, placebo-controlled study of sublingual immunotherapy in patients with latex-induced urticaria: a 12-month study. Br J Dermatol. 2007;156:674-681.

7. Lee EE, Maibach HI. Treatment of urticaria. An evidence-based evaluation of antihistamines. Am J Clin Dermatol. 2001;2:27-32.

8. Humphreys F, Hunter JA. The characteristics of urticaria in 390 patients. Br J Dermatol. 1998;138:635-638.

9. Serhat Inaloz H, Ozturk S, Akcali C, et al. Low-dose and short-term cyclosporine treatment in patients with chronic idiopathic urticaria: A clinical and immunological evaluation. J Dermatol. 2008;35:276-282.

10. Erbagci Z. The leukotriene receptor antagonist montelukast in the treatment of chronic idiopathic urticaria. A single-blind, placebo-controlled, crossover clinical study. J Allergy Clin Immunol. 2002;110:484-488.

11. Kostis JB, Kim HJ, Rusnak J, et al. Incidence and characteristics of angioedema associated with enalapril. Arch Intern Med. 2005;165:1637-1642.

12. Yusuf S, Teo KK, Pogue J, et al. ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-1559.

13. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115(3 Suppl 2):s483-s523.

14. Bas M, Kirchhartz N, Hochfeld J, et al. Potential role of vasomotor effects of fibrinogen in bradykinin-induced angioedema. J Allergy Clin Immunol. 2008;121:969e2-975e2.

15. Sica DA, Black HR. Angioedema in heart failure: occurrence with ACE inhibitors and safety of angiotensin receptor blocker therapy. Congest Heart Fail. 2002;8:334-341.

16. Banerji A, Clark S, Blanda M, et al. Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department. Ann Allergy Asthma Immunol. 2008;100:327-332.

17. Cicardi M, Zingale LC, Zanichelli A, et al. The use of plasma-derived C1 inhibitor in the treatment of hereditary angioedema. Expert Opin Pharmacother. 2007;8:3173-3181.

18. Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol. 2008;100:153-161.

19. US Food and Drug Administration. Advisory Committee Briefing Document. Kalbitor (ecallantide) for acute attacks of hereditary angioedema. Available at: http://www.fda.gov/ohrms/dockets/AC/09/briefing/2009-4413b1-03-Dyax.pdf. Accessed May 5, 2009.

20. Schneider L, Lumry W, Vegh A, et al. Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol. 2007;120:416-422.

21. Ellis Simonsen SM, van Orman ER, Hatch BE, et al. Cellulitis incidence in a defined population. Epidemiol Infect. 2006;134:293-299.

22. Stevens DL, Bisno AL, Chambers HF, et al. Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41:1373-1406.

23. Morris A. What are the benefits of treatments? Cellulitis and erysipelas. BMJ Clin Evid. 2005;13:2066-2069.

24. Murray H, Stiell I, Wells G. Treatment failure in emergency department patients with cellulitis. CJEM. 2005;7:228-234.

25. Meier DE, Nkor SK, Aasa D, et al. Prospective randomized comparison of two preoperative skin preparation techniques in a developing world country. World J Surg. 2001;25:441-443.

26. Giordano PA, Elston D, Akinlade BK, et al. Cefdinir vs. cephalexin for mild to moderate uncomplicated skin and skin structure infections in adolescents and adults. Curr Med Res Opin. 2006;22:2419-2428.

27. Halpern J, Holder R, Langford NJ. Ethnicity and other risk factors for acute lower limb cellulitis: a U.K.-based prospective case-control study. Br J Dermatol. 2008;158:1288-1292.

28. Lin YT, Lu PW. Retrospective study of pediatric facial cellulitis of odontogenic origin. Pediatr Infect Dis J. 2006;25:339-342.

29. Rajendran PM, Young D, Maurer T, et al. Randomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob Agents Chemo. 2007;51:4044-4048.

30. Schneck J, Fagot JP, Sekula P, et al. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008;58:33-40.

31. Chan HL, Stern RS, Arndt KA, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol. 1990;126:43-47.

32. Hazin R, Ibrahimi OA, Hazin MI, et al. Stevens-Johnson syndrome: pathogenesis, diagnosis, and management. Ann Med, 2008;40:129-138.

33. Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428:486.-

34. Jette N, Hemming K, Hutton JL, et al. Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2008;(3):DC001417.-

35. Gürcan HM, Ahmed AR. Efficacy of various intravenous immunoglobulin therapy protocols in auto-immune and chronic inflammatory disorders. Ann Pharmacother. 2007;41:812-523.

36. Strom BL, Carson JL, Halpern AC, et al. A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures. Arch Dermatol. 1991;127:831-838.

37. Gravante G, Delogu D, Marianetti M, et al. Toxic epidermal necrolysis and Steven-Johnson syndrome: 11-years experience and outcome. Eur Rev Med Pharmacol Sci. 2007;11:119-127.

Chronic urticaria, trigger unknown

Although acute urticaria is responsive to treatment, chronic urticaria—lesions that do not resolve after 6 weeks—poses a greater challenge. In up to 80% of cases of chronic urticaria, no identifiable trigger is found.^3,8 Long-term treatment of patients with this chronic condition, including lifestyle changes (to avoid environmental or dietary triggers) and a medication regimen for 6 months or more, leads to complete resolution of symptoms in most cases.^7,8

Angioedema: Less common, more dangerous

Angioedema is part of the same disease spectrum as urticaria, but it affects the deeper tissues—involving mucosal and submucosal swelling. Angioedema affects just 0.1% to 0.2% of the general population, but up to 15% of patients with urticaria.⁸

The risk increases with the use of ACE inhibitors; for every 1000 patients taking ACE inhibitors, 0.4 to 3.5 develop angioedema.¹¹ A recent double-blind study involving 25,642 patients being treated with ACE inhibitors revealed that those taking a combination of ACE inhibitors were more likely to develop angioedema than those on monotherapy.¹²

FAST TRACK

Raised erythematous plaques are the cardinal features of cellulitis.

Angioedema is characterized by the sudden appearance of painful, localized erythematous wheals with central blanching.¹³ It results from increased vascular permeability in capillaries of the dermis, which leads to fluid leakage.^13,14 Increased accumulation of fluids from the vessels of the skin results in rapidly developing nonpitting edema that most often affects the hands, face (and lips), neck, and oropharynx (FIGURE 1).¹⁴ Although the head and neck are the most commonly involved areas, angioedema can also affect the digestive tract, leading to nausea, vomiting, diarrhea, and abdominal pain secondary to bowel edema.¹³

FIGURE 1
Angioedema: A look at the most commonly affected areas

Airway management is imperative

In severe cases of angioedema, involvement of the oral mucosa results in stridor, followed by upper airway obstruction. To avoid hypoxemia and death,^13,14 rapid preparation for emergency intervention to maintain the airway is critical; mortality can be as high as 30% in patients with airway compromise.^13,15 In severe cases in which edema engulfs the oropharynx, oral intubation is often impossible, and nasotracheal intubation may be warranted.^15,16 A failure to maintain adequate airway function via nasotracheal intubation may signal the need for an emergency tracheotomy.^15,16

Is the angioedema hereditary or acquired?

Hereditary and acquired angioedema are treated differently. After ensuring that the patient has a patent airway, distinguishing between them is critical. Hereditary angioedema is the result of an inherited deficiency of plasma protein C1 inhibitor (C1-INH). Acquired angioedema is typically caused by enhanced consumption of endogenous C1-INH,^13,17 leading to a net deficit of circulating C1-INH, and can be triggered by food, pharmacologic agents, and, occasionally, by systemic disorders.¹³ African Americans and patients with renal impairment appear to be at increased risk for acquired angioedema.¹³ In both hereditary and acquired angioiedema, decreased levels of C1-INH lead to disruption of the complement pathway.

FAST TRACK

Suspect Stevens-Johnson syndrome? Do a skin biopsy and order immunofluorescence studies to rule out conditions unrelated to drug reactions.

Although the clinical presentation of acquired and hereditary angioedema is similar, a focused patient history can be used to distinguish between them. Age, health status, and medication history are the key considerations. Hereditary angioedema most commonly occurs—in recurrent attacks after minor trauma—in children with no underlying disease, with worsening symptoms during puberty. Acquired angioedema is generally seen in adult and elderly patients with malignancies or other underlying disorders.

Mild to moderate cases of acquired angioedema respond well to oral corticosteroids and antihistamines. Severe cases often require administration of subcutaneous epinephrine, followed by IV steroids. Management of hereditary angioedema should include C1-INH-containing fresh frozen plasma,^13,16,18 although fresh frozen plasma can be used if plasma with C1-INH is not available.¹³

While oral corticosteroids and anti-histamines may be effective adjunctive therapy for hereditary angioedema, they are not likely to reverse acute attacks in this patient population. IV diphenhydramine (50-100 mg) or IV cimetidine (300 mg) every 6 to 8 hours is a reasonable therapeutic regimen for acute attacks of hereditary angioedema.

A recent randomized double-blind trial involving 40 patients with hereditary angioedema studied the administration of ecallantide, a kallikrein inhibitor for which US Food and Drug Administration approval is pending.¹⁹ Nearly 3 out of 4 of those who received ecallantide (72.5%) for acute attacks of angioedema showed significant improvement within 4 hours.²⁰ The use of kallikrein inhibitors, which target inflammatory blood components, is not widespread, but may hold promise for the treatment of hereditary angioedema.²⁰