Histopathology of drug eruptions-general criteria, common patterns, and differential diagnosis
Keywords:
drug eruptions, histopathology, skinAbstract
Drug eruptions are among the most common inflammatory diseases of the skin and also among those biopsied most often. Yet, the value of histopathologic examination of drug eruptions has often been disputed. One reason is that the spectrum of histopathologic changes in drug eruptions is broad. Nevertheless, each histopathologic pattern assumed by drug eruptions has a limited number of differential diagnoses, and numerous criteria and clues are available to distinguish drug eruptions from other diseases associated with those patterns. By recognition of common patterns, consideration of differential diagnoses, and attention to distinct clues, a histopathologic diagnosis of drug eruption can usually be made with confidence.
References
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2. Justiniano H, Berlingeri-Ramos AC, SÁnchez JL. Pattern analysis of drug-induced skin diseases. Am J Dermatopathol 2008;30(4):352-9. CrossRef
3. Breathnach SM. Drug reactions. In: Burns T, Breathnach S, Cox N, Griffiths C (eds.) Rook’s Textbook of Dermatology. 7th ed. Malden, Oxford, Carlton: Blackwell Science, 2004:73.21.
4. Bigby M. Rates of cutaneous reactions to drugs. Arch Dermatol 2001;137(6):765-70.
5. Bork K. Arzneimittelreaktionen. In: Braun-Falco O, Plewig G, Wolff HH, Burgdorf WHC, Landthaler M (eds.) Dermatologie und Venerologie 5th ed. Heidelberg: Springer, 2005:432.
6. Revuz J, Valeyrie-Allanore L. Drug reactions. In: Bologna JL, Jorizzo JL, Rapini RP (eds.) Dermatology. Edinburgh, London, New York, Oxford, Philadelphia, St. Louis, Sydney, Toronto: Mosby, 2003:337.
7. Wong GA, Shear NH. Is a drug alone sufficient to cause the drug hypersensitivity syndrome? Arch Dermatol 2004;140(2):226-30.
8. Morimoto T, Sato T, Matsuoka, et al. Trimethoprim-sulfamethoxazole-induced hypersensitivity syndrome associated with reactivation of human herpesvirus-6. Intern Med 2006;45(2):101-5.
9. Carlson JA, Perlmutter A, Tobin E, Richardson D, Rohwedder A. Adverse antibiotic-induced eruptions associated with Epstein Barr virus infection and showing Kikuchi-Fujimoto disease-like histology. Am J Dermatopathol 2006;28(1):48-55.
10. Weedon D. Skin Pathology. 3rd ed. London, Edinburgh, New York: Churchill Livingstone Elsevier, 2010:607-31.
11. Ackerman AB, Suringa DW. Multinucleate epidermal cells in measles. Arch Dermatol 1971;103(2):180-1.
12. Ackerman AB, Jacobson M, Vitale P. Clues to Diagnosis in Dermatopathology. Chicago: ASCP Press, 1991:77-80.
13. Naim M, Weyers W, Metze D. Histopathologic features of exanthematous drug eruptions of the macular and papular type. Am J Dermatopathol 2011 Jul 8 [Epub ahead of print]
14. Schreiber MM, McGregor JC. Pseudolymphoma syndrome: a sensitivity to anticonvulsant drugs. Arch Dermatol 1968;97(3):297-300.
15. Welykyj S, Gradini R, Nakao J, Massa M. Carbamazepine-induced eruption histologically mimicking mycosis fungoides. J Cutan Pathol 1990;17(2):111-6.
16. Rijlaarsdam U, Scheffer E, Meijer CJ, Kruyswijk MR, Willemze R. Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy. J Am Acad Dermatol 1991;24(2):216-20.
17. Alvarez-Ruiz S, Delgado Y, AragÜes M, Fraga J, SÁnchez-PÉrez J, FernÁndez-Herrera J. Erupciones de tipo micosis fungoide inducidas por carbamazepina. Actas Dermo-SifiliogrÁficas 2006;97(1):43-7.
18. Gerson D, Sriganeshan V, Alexis JB. Cutaneous drug eruptions: a 5-year experience. J Am Acad Dermatol 2008;59(6):995-9. CrossRef
19. Hann SK, Rhoe BS, Kang WH, Park YK. Self limited dermal invasion of keratinocytes in maculopapular eruptions after systemic chemotherapy. J Dermatol 1993;20(2):94-101.
20. Yang CH, Yang LJ, Jaing TH, Chan HL. Toxic epidermal necrolysis following combination of methotrexate and trimethoprim-sulfamethoxazole. Int J Dermatol 2000;39(8):621-3.
21. Wells JM, Weedon D, Muir JB. Erythema multiforme: a case with unusual histopathological features. Australas J Dermatol 2000;41(4):257-9.
22. Markopoulos AK, Belazi M, Mourellou O, Kapetis E, Trigonidis G. Eosinophils in oral and cutaneous lesions of erythema multiforme. Ann Dent 1994;53(2):30-3.
23. Rzany B, Hering O, Mockenhaupt M, et al. Histopathological and epidemiological characteristics of patients with erythema exsudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 1996;135(1):6-11.
24. Patterson JW, Parsons JM, Blaylock WK, Mills AS. Eosinophils in skin lesions of erythema multiforme. Arch Pathol Lab Med 1989;113(1):36-9.
25. Zohdi-Mofid M, Horn TD. Acrosyringeal concentration of necrotic keratinocytes in erythema multiforme: a clue to drug etiology. Clinicopathologic review of 29 cases. J Cutan Pathol 1996;24(4):235-40.
26. Kohler S, Hendrickson MR, Chao NJ, Smoller BR. Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease. Am J Surg Pathol 1997;21(9):988-96.
27. Massi D, Franchi A, Pimpinelli N, Laszlo D, Bosi A, Santucci M. A reappraisal of the histopathologic criteria for the diagnosis of cutaneous allogenic acute graft-vs-host-disease. Am J Clin Pathol 1999;112(6):791-800.
28. Bridge AT, Nelson RP, Schwartz JE, Mirowski GW, Billings SD. Histological evaluation of acute mucocutaneous graft-versus-host disease in nonmyeloablative hematologic stem cell transplants with an observation predicting an increased risk of progression to chronic graft-versus-host disease. Am J Dermatopathol 2007;29(1):1-6.
29. Marra DE, McKee PH, Nghiem P. Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus host disease. J Am Acad Dermatol 2004;51(4):543-6.
30. Firoz BF, Lee SJ, Nghiem P, Qureshi AA. Role of skin biopsy to confirm suspected acute graft-vs-host disease: results of decision analysis. Arch Dermatol 2006;142(2):175-82.
31. West AJ, Berger TG, LeBoit PE. A comparative histopathologic study of photodistributed and nonphotodistributed lichenoid drug eruptions. J Am Acad Dermatol 1990;239(4):689-93.
32. Ackerman AB. Histologic Diagnosis of Inflammatory Skin Diseases. Philadelphia: Lea & Febiger, 1978:210.
33. Van den Haute V, Antoine JL, Lachapelle JM. Histopathological discriminant criteria between lichenoid drug eruption and idiopathic lichen planus: retrospective study on selected samples. Dermatologica 1989;179(1):10-13.
34. Ackerman AB, Briggs PL, Bravo F. Differential Diagnosis in Dermatopathology III. Philadelphia, London: Lea & Febiger, 1993:18-21.
35. Gonzalez JG, Marcus MD, Santa Cruz DJ. Giant cell lichenoid dermatitis. J Am Acad Dermatol 1986;15(1):87-92.
36. Elhem Khelifa-Hamdani M, Touati-Serraj J, Perriard PC, Saurat JH, Kaya G. Giant cell lichenoid dermatitis in a patient with baboon syndrome. J Cutan Pathol 2008;35(Suppl 1):17-9.
37. Furness PN, Goodfield MJ, MacLennan KA, Stevens A, Millard LG. Severe cutaneous reactions to captopril and enalapril: histological study and comparison with early mycosis fungoides. J Clin Pathol 1986;39(8):902-7.
38. Kardaun SH, Scheffer E, Vermeer BJ. Drug-induced pseudolymphomatous skin reactions. Br J Dermatol 1988;118(4):845-52.
39. Magro CM, Crowson AN. Drugs with antihistaminic properties as a cause of atypical cutaneous lymphoid hyperplasia. J Am Acad Dermatol 1995;32(3):419-28.
40. Gordon KB, Guitart J, Kuzel T, et al. Pseudo-mycosis fungoides in a patient taking clonazepam and fluoxetine. J Am Acad Dermatol 1996;34(2):304-6.
41. Clark SH, Duvic M, Prieto VG. Mycosis fungoides-like reaction in a patient treated with Gleevec. J Cutan Pathol 2003;30(4):279-81.
42. Ackerman AB, Guo Y. Vitale P, Vossaert K. Clues to Diagnosis in Dermatopathology III. Chicago: ASCP Press, 1998:53-56.
43. Boer A, Misago N, Wolter M, Kiryu H, Wang XD, Ackerman AB. Prurigo pigmentosa: new observations and comprehensive review. Dermatopathology: Practical & Conceptual 2002;8(3).
44. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol 2010;37(12):1220-29. CrossRef
45. Magro CM, Crowson AN, Schapiro BL. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity. J Cutan Pathol 1998;25(2):72-8.
46. Bahrami S, Malone JC, Webb KG, Callen JP. Tissue eosinophilia as an indicator of drug-induced cutaneous small-vessel vasculitis. Arch Dermatol 2006;142(2):155-61.
2. Justiniano H, Berlingeri-Ramos AC, SÁnchez JL. Pattern analysis of drug-induced skin diseases. Am J Dermatopathol 2008;30(4):352-9. CrossRef
3. Breathnach SM. Drug reactions. In: Burns T, Breathnach S, Cox N, Griffiths C (eds.) Rook’s Textbook of Dermatology. 7th ed. Malden, Oxford, Carlton: Blackwell Science, 2004:73.21.
4. Bigby M. Rates of cutaneous reactions to drugs. Arch Dermatol 2001;137(6):765-70.
5. Bork K. Arzneimittelreaktionen. In: Braun-Falco O, Plewig G, Wolff HH, Burgdorf WHC, Landthaler M (eds.) Dermatologie und Venerologie 5th ed. Heidelberg: Springer, 2005:432.
6. Revuz J, Valeyrie-Allanore L. Drug reactions. In: Bologna JL, Jorizzo JL, Rapini RP (eds.) Dermatology. Edinburgh, London, New York, Oxford, Philadelphia, St. Louis, Sydney, Toronto: Mosby, 2003:337.
7. Wong GA, Shear NH. Is a drug alone sufficient to cause the drug hypersensitivity syndrome? Arch Dermatol 2004;140(2):226-30.
8. Morimoto T, Sato T, Matsuoka, et al. Trimethoprim-sulfamethoxazole-induced hypersensitivity syndrome associated with reactivation of human herpesvirus-6. Intern Med 2006;45(2):101-5.
9. Carlson JA, Perlmutter A, Tobin E, Richardson D, Rohwedder A. Adverse antibiotic-induced eruptions associated with Epstein Barr virus infection and showing Kikuchi-Fujimoto disease-like histology. Am J Dermatopathol 2006;28(1):48-55.
10. Weedon D. Skin Pathology. 3rd ed. London, Edinburgh, New York: Churchill Livingstone Elsevier, 2010:607-31.
11. Ackerman AB, Suringa DW. Multinucleate epidermal cells in measles. Arch Dermatol 1971;103(2):180-1.
12. Ackerman AB, Jacobson M, Vitale P. Clues to Diagnosis in Dermatopathology. Chicago: ASCP Press, 1991:77-80.
13. Naim M, Weyers W, Metze D. Histopathologic features of exanthematous drug eruptions of the macular and papular type. Am J Dermatopathol 2011 Jul 8 [Epub ahead of print]
14. Schreiber MM, McGregor JC. Pseudolymphoma syndrome: a sensitivity to anticonvulsant drugs. Arch Dermatol 1968;97(3):297-300.
15. Welykyj S, Gradini R, Nakao J, Massa M. Carbamazepine-induced eruption histologically mimicking mycosis fungoides. J Cutan Pathol 1990;17(2):111-6.
16. Rijlaarsdam U, Scheffer E, Meijer CJ, Kruyswijk MR, Willemze R. Mycosis fungoides-like lesions associated with phenytoin and carbamazepine therapy. J Am Acad Dermatol 1991;24(2):216-20.
17. Alvarez-Ruiz S, Delgado Y, AragÜes M, Fraga J, SÁnchez-PÉrez J, FernÁndez-Herrera J. Erupciones de tipo micosis fungoide inducidas por carbamazepina. Actas Dermo-SifiliogrÁficas 2006;97(1):43-7.
18. Gerson D, Sriganeshan V, Alexis JB. Cutaneous drug eruptions: a 5-year experience. J Am Acad Dermatol 2008;59(6):995-9. CrossRef
19. Hann SK, Rhoe BS, Kang WH, Park YK. Self limited dermal invasion of keratinocytes in maculopapular eruptions after systemic chemotherapy. J Dermatol 1993;20(2):94-101.
20. Yang CH, Yang LJ, Jaing TH, Chan HL. Toxic epidermal necrolysis following combination of methotrexate and trimethoprim-sulfamethoxazole. Int J Dermatol 2000;39(8):621-3.
21. Wells JM, Weedon D, Muir JB. Erythema multiforme: a case with unusual histopathological features. Australas J Dermatol 2000;41(4):257-9.
22. Markopoulos AK, Belazi M, Mourellou O, Kapetis E, Trigonidis G. Eosinophils in oral and cutaneous lesions of erythema multiforme. Ann Dent 1994;53(2):30-3.
23. Rzany B, Hering O, Mockenhaupt M, et al. Histopathological and epidemiological characteristics of patients with erythema exsudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 1996;135(1):6-11.
24. Patterson JW, Parsons JM, Blaylock WK, Mills AS. Eosinophils in skin lesions of erythema multiforme. Arch Pathol Lab Med 1989;113(1):36-9.
25. Zohdi-Mofid M, Horn TD. Acrosyringeal concentration of necrotic keratinocytes in erythema multiforme: a clue to drug etiology. Clinicopathologic review of 29 cases. J Cutan Pathol 1996;24(4):235-40.
26. Kohler S, Hendrickson MR, Chao NJ, Smoller BR. Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease. Am J Surg Pathol 1997;21(9):988-96.
27. Massi D, Franchi A, Pimpinelli N, Laszlo D, Bosi A, Santucci M. A reappraisal of the histopathologic criteria for the diagnosis of cutaneous allogenic acute graft-vs-host-disease. Am J Clin Pathol 1999;112(6):791-800.
28. Bridge AT, Nelson RP, Schwartz JE, Mirowski GW, Billings SD. Histological evaluation of acute mucocutaneous graft-versus-host disease in nonmyeloablative hematologic stem cell transplants with an observation predicting an increased risk of progression to chronic graft-versus-host disease. Am J Dermatopathol 2007;29(1):1-6.
29. Marra DE, McKee PH, Nghiem P. Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus host disease. J Am Acad Dermatol 2004;51(4):543-6.
30. Firoz BF, Lee SJ, Nghiem P, Qureshi AA. Role of skin biopsy to confirm suspected acute graft-vs-host disease: results of decision analysis. Arch Dermatol 2006;142(2):175-82.
31. West AJ, Berger TG, LeBoit PE. A comparative histopathologic study of photodistributed and nonphotodistributed lichenoid drug eruptions. J Am Acad Dermatol 1990;239(4):689-93.
32. Ackerman AB. Histologic Diagnosis of Inflammatory Skin Diseases. Philadelphia: Lea & Febiger, 1978:210.
33. Van den Haute V, Antoine JL, Lachapelle JM. Histopathological discriminant criteria between lichenoid drug eruption and idiopathic lichen planus: retrospective study on selected samples. Dermatologica 1989;179(1):10-13.
34. Ackerman AB, Briggs PL, Bravo F. Differential Diagnosis in Dermatopathology III. Philadelphia, London: Lea & Febiger, 1993:18-21.
35. Gonzalez JG, Marcus MD, Santa Cruz DJ. Giant cell lichenoid dermatitis. J Am Acad Dermatol 1986;15(1):87-92.
36. Elhem Khelifa-Hamdani M, Touati-Serraj J, Perriard PC, Saurat JH, Kaya G. Giant cell lichenoid dermatitis in a patient with baboon syndrome. J Cutan Pathol 2008;35(Suppl 1):17-9.
37. Furness PN, Goodfield MJ, MacLennan KA, Stevens A, Millard LG. Severe cutaneous reactions to captopril and enalapril: histological study and comparison with early mycosis fungoides. J Clin Pathol 1986;39(8):902-7.
38. Kardaun SH, Scheffer E, Vermeer BJ. Drug-induced pseudolymphomatous skin reactions. Br J Dermatol 1988;118(4):845-52.
39. Magro CM, Crowson AN. Drugs with antihistaminic properties as a cause of atypical cutaneous lymphoid hyperplasia. J Am Acad Dermatol 1995;32(3):419-28.
40. Gordon KB, Guitart J, Kuzel T, et al. Pseudo-mycosis fungoides in a patient taking clonazepam and fluoxetine. J Am Acad Dermatol 1996;34(2):304-6.
41. Clark SH, Duvic M, Prieto VG. Mycosis fungoides-like reaction in a patient treated with Gleevec. J Cutan Pathol 2003;30(4):279-81.
42. Ackerman AB, Guo Y. Vitale P, Vossaert K. Clues to Diagnosis in Dermatopathology III. Chicago: ASCP Press, 1998:53-56.
43. Boer A, Misago N, Wolter M, Kiryu H, Wang XD, Ackerman AB. Prurigo pigmentosa: new observations and comprehensive review. Dermatopathology: Practical & Conceptual 2002;8(3).
44. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol 2010;37(12):1220-29. CrossRef
45. Magro CM, Crowson AN, Schapiro BL. The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity. J Cutan Pathol 1998;25(2):72-8.
46. Bahrami S, Malone JC, Webb KG, Callen JP. Tissue eosinophilia as an indicator of drug-induced cutaneous small-vessel vasculitis. Arch Dermatol 2006;142(2):155-61.
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Weyers W, Metze D. Histopathology of drug eruptions-general criteria, common patterns, and differential diagnosis. Dermatol Pract Concept. Published online October 31, 2011:33-47. doi:10.5826/dpc.0101a09
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