Primary vesicular-bullous skin lesions include vesicles and bullae. Secondary lesions may include scale, crust, milia, and scarring. These conditions are classified by depth of skin involvement.
Summary
Vesicles
Vesicles are circumscribed, fluid-filled epidermal elevations <1 cm in diameter that:[1]
- Contain serous exudates or serum mixed with blood, or are seropurulent in character
- Are discrete, grouped (e.g., herpetic infection), irregularly distributed, or linear as in Rhus dermatitis (e.g., poison ivy)
- Are short-lived, either breaking spontaneously or evolving into bullae through enlargement or coalescence.
Bullae
Bullae are blisters >1 cm in diameter containing serous or seropurulent fluid. When bullae are located within the epidermis, they present with thin and flaccid walls, which rupture resulting in erosions, scale, and crust. Erosions are the result of loss of the superficial layers of the epidermis and, in the absence of secondary infection, typically heal without scarring.
The fragility of a blister is often related to anatomical location (e.g., intraoral blisters typically present as erosions due to the fragility of mucosa, irrespective of localization of the bullae within or below the epidermis).[2] Friction blisters occur below the corneal layer, but present as tense bullae due to the thick stratum corneum of volar skin.
Bullae located in the epidermis are flaccid and rupture easily. The Nikolsky sign may be demonstrated in a patient with intraepithelial bullae by the shearing off of the epithelium with lateral pressure on intact skin. However, the majority of experts no longer recommend performing the Nikolsky sign, noting that there are other tools to measure disease activity.[3] For bullae developing in the basement membrane, the Asboe-Hansen sign is often elicited by the extension of the blister into unblistered skin when pressure is applied to the top of the blister.[1] These signs serve to demonstrate that in some diseases (e.g., pemphigus vulgaris and bullous pemphigoid) the extent of blistering is greater than observed by inspection.
Subepidermal bullae are tense. Subepidermal blisters may result in ulceration and scarring following rupture. Ulcers occur when both the epidermis and superficial dermis are lost, either as a consequence of the blistering process (e.g., epidermolysis bullosa), or resulting from secondary infection and/or trauma. Pigment is lost in the ulcer base as the melanocytes are shed in the blister roof.Images
Distinctions
Clinical features that should be noted when evaluating a patient with a blistering process are the presence of scale, crust, milia, and scarring.
- Scale is laminated masses of keratin.[1] It may indicate a superficial blistering process such as pemphigus, infection-mediated desquamations, and drug eruptions (e.g., toxic epidermal necrolysis).
- Crust is dried exudate composed of serum, cells, and often bacteria. It may be found overlying erosions in pemphigus.
- Milia are white keratinous cysts 1 mm to 4 mm in diameter. When present in a blistering process they may suggest epidermolysis bullosa or porphyria cutanea tarda.
- Scarring is due to a blister developing at either the dermal-epidermal junction (e.g., basement membrane zone) or the dermis. The presence of urticarial papules, plaques, and/or excoriations, even in the absence of blisters, may be an early indicator of autoimmune blistering diseases (e.g., bullous pemphigoid or dermatitis herpetiformis).
Classification
Blisters occur at various depths in the epidermis or dermis and may be classified based on the depth of the skin involved. A broad classification divides blisters into those arising within the epidermis (intraepidermal, which includes subcorneal) and those that develop below the epidermis (subepidermal, which includes the basement membrane zone).
Last updated
Library
Pemphigus vulgaris (PV)
Pemphigus vulgaris (PV)
Pemphigus vulgaris (PV)
Pemphigus vulgaris (PV)
Impetigo of arm presenting as an erosion
Florid bullous impetigo
Lesions caused by herpes simplex virus Type-1 (HSV-1)
HSV-penile vesicular lesion
HSV-labial ulceration
Target lesions on the face and mucosal erosions with crusting due to HSV-1 recurrence
Varicella zoster virus (VZV)
Varicella zoster virus (VZV)
Varicella lesion on hard palate of a young patient
Typical vesicular rash of primary varicella; note that lesions are in different stages
Scabie mite under 10 x power
Characteristic linear burrows in skin
Recessive dystrophic epidermolysis bullosa (DEB)
Recessive dystrophic epidermolysis bullosa (DEB)
Miliaria crystallina in hospitalized febrile patient
Mastocytosis (urticaria pigmentosa)
Palmar target lesions
Target and targetoid lesions
Bullous erythema multiforme (EM)
Bullous erythema multiforme (EM)
Disseminated varicella zoster virus (VZV)
Bullous pemphigoid (BP)
Bullous pemphigoid (BP)
Toxic epidermolytic necrolysis (TEN)
Toxic epidermolytic necrolysis (TEN)
Citations
Berger TG, James WD, Elston DM. Andrew's diseases of the skin, clinical dermatology, 10th edition. WB Saunders; 2008.
Joly P, Horvath B, Patsatsi alpha, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol. 2020 Sep;34(9):1900-13.[Abstract][Full Text]
Fine JD, Bruckner-Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103-26.[Abstract][Full Text]
1. Berger TG, James WD, Elston DM. Andrew's diseases of the skin, clinical dermatology, 10th edition. WB Saunders; 2008.
2. Harper J, Oranje A, Prose N. Textbook of pediatric dermatology, Volume 1. Blackwell Science; 2000.
3. Joly P, Horvath B, Patsatsi alpha, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol. 2020 Sep;34(9):1900-13.[Abstract][Full Text]
4. Jaworsky C, Murphy G. Special techniques in dermatology. Arch Dermatol. 1989 Jul;125(7):963-74.[Abstract]
5. Miller JM, Binnicker MJ, Campbell S, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis. 2018 Aug 31;67(6):e1-94.[Abstract][Full Text]
6. Lowy G. Sexually transmitted diseases in children. Pediatr Dermatol. 1992 Dec;9(4):329-34.[Abstract]
7. Bolognia J, Jorizzo JL, Rapini RP. Dermatology, 2nd edition, volume 1. Philadelphia, PA: Mosby Saunders; 2008.
8. Robinson CR, Doane FW, Rhodes AJ. Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957; isolation of group A Coxsackie virus. Can Med Assoc J. 1958 Oct 15;79(8):615-21.[Abstract][Full Text]
9. Huang YA, Howard-Jones AR, Durrani S, et al. Monkeypox: a clinical update for paediatricians. J Paediatr Child Health. 2022 Sep;58(9):1532-8.[Abstract][Full Text]
10. McCollum AM, Shelus V, Hill A, et al. Epidemiology of human mpox - worldwide, 2018-2021. MMWR Morb Mortal Wkly Rep. 2023 Jan 20;72(3):68-72.[Abstract][Full Text]
11. World Health Organization. Clinical management and infection prevention and control for monkeypox: interim rapid response guidance. Jun 2022 [internet publication].[Full Text]
12. World Health Organization. Mpox. Aug 2024 [internet publication].[Full Text]
13. Wozniacka A, Hawro T, Schwartz RA. Bullous scabies: a diagnostic challenge. Cutis. 2008 Nov;82(5):350-2.[Abstract]
14. Weinstock MA, Kempton SA. Case report: teledermatology and epiluminescence microscopy for the diagnosis of scabies. Cutis. 2000 Jul;66(1):61-2.[Abstract]
15. Uitto J, Richard G. Progress in epidermolysis bullosa: genetic classifications and clinical implications. Am J Med Genet C Semin Med Genet. 2004 Nov 15;131C(1):61-74.[Abstract]
16. Fine JD, Bruckner-Tuderman L, Eady RA, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014 Jun;70(6):1103-26.[Abstract][Full Text]
17. Elder DE, Elenitsas R, Johnson BL Jr, et al. Lever's histopathology of the skin. 10th edition. Philadelphia, PA: Lippincott Williams and Wilkins; 2009.
18. Ramdial PK, Naidoo DK. Drug-induced skin pathology. J Clin Pathol. 2009 Jun;62(6):493-504.[Abstract][Full Text]
19. Hoeger PH, Harper JI. Neonatal erythroderma: differential diagnosis and management of the "red baby." Arch Dis Child. 1998 Aug;79(2):186-91.[Abstract][Full Text]
20. Alto WA, Clarcq L. Cutaneous and systemic manifestations of mastocytosis. Am Fam Physician. 1999 Jun;59(11):3047-54;3059-60.[Abstract][Full Text]
21. Wang L, Varghese S, Bassir F, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review of PubMed/MEDLINE case reports from 1980 to 2020. Front Med (Lausanne). 2022 Aug 24;9:949520.[Abstract][Full Text]
22. Lane K, Lumbang W. Pruritic blisters on legs and feet. J Fam Pract. 2008 Mar;57(3):177-80.[Abstract]
23. Nousari HC, Anhalt GJ. Pemphigus and bullous pemphigoid. Lancet. 1999 Aug 21;354(9179):667-72.[Abstract]
24. Yeh SW, Ahmed B, Sami N, et al. Blistering disorders: diagnosis and treatment. Dermatol Ther. 2003;16(3):214-23.[Abstract]
25. Bickle K, Roark TR, Hsu S. Autoimmune bullous disease: a review. Am Fam Physician. 2002 May 1;65(9):1861-70.[Abstract][Full Text]
26. Mihai S, Sitaru C. Immunopathology and molecular diagnosis of autoimmune bullous diseases. J Cell Mol Med. 2007 May-Jun;11(3):462-81.[Abstract][Full Text]
27. Liu SD, Chen WT, Chi CC. Association between medication use and bullous pemphigoid: a systematic review and meta-analysis. JAMA Dermatol. 2020 Aug 1;156(8):891-900.[Abstract][Full Text]
28. Schwartzman G, Simpson MM, Jones R, et al. Anti-PD1 immune checkpoint inhibitor-induced bullous pemphigoid in metastatic melanoma and non-small cell lung cancer. Cutis. 2020 Jun;105(6):E9-12.[Abstract]
29. Avram MA, Gobel V, Sepehr A. Case records of the Massachusetts General Hospital. Case 30-2007: a newborn girl with skin lesions. N Engl J Med. 2007 Sep 27;357(13):1327-35.
30. Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, et al. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med. 2000 Mar 2;342(9):635-45.[Abstract]
31. Howell ER, Phillips CM. Cutaneous manifestations of Staphylococcus aureus disease. Skinmed. 2007 Nov-Dec;6(6):274-9.[Abstract]
32. Fisler RE, Saeb M, Liang MG, et al. Childhood bullous pemphigoid: a clinicopathologic study and review of the literature. Am J Dermatopathol. 2003 Jun;25(3):183-9.[Abstract]
33. Kridin K, Bergman R. Association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors in patients with diabetes: estimating the risk of the new agents and characterizing the patients. JAMA Dermatol. 2018 Oct 1;154(10):1152-8.[Abstract]
34. Lee SG, Lee HJ, Yoon MS, et al. Association of dipeptidyl peptidase 4 inhibitor use with risk of bullous pemphigoid in patients with diabetes. JAMA Dermatol. 2019 Feb 1;155(2):172-7.[Abstract]
35. Benzaquen M, Borradori L, Berbis P, et al. Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: retrospective multicenter case-control study from France and Switzerland. J Am Acad Dermatol. 2018 Jun;78(6):1090-6.[Abstract]
36. Muller UR, Haeberli G. The problem of anaphylaxis and mastocytosis. Curr Allergy Asthma Rep. 2009 Jan;9(1):64-70.[Abstract]
37. Zimmermann S, Sekula P, Venhoff M, et al. Systemic immunomodulating therapies for Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2017 Jun 1;153(6):514-22.[Abstract][Full Text]
38. Schneider JA, Cohen PR. Stevens-Johnson syndrome and toxic epidermal necrolysis: a concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017 Jun;34(6):1235-44.[Abstract][Full Text]
39. Meuwissen ME, Mancini GM. Neurological findings in incontinentia pigmenti: a review. Eur J Med Genet. 2012 May;55(5):323-31.[Abstract]
40. Hendricks WM. Pellagra and pellagralike dermatoses: etiology, differential diagnosis, dermatopathology, and treatment. Semin Dermatol. 1991 Dec;10(4):282-92.[Abstract]
41. Centers for Disease Control and Prevention. Clinical features of mpox. Sep 2024 [internet publication].[Full Text]
42. Li P, Li J, Ayada I, et al. Clinical features, antiviral treatment, and patient outcomes: a systematic review and comparative analysis of the previous and the 2022 mpox outbreaks. J Infect Dis. 2023 Aug 16;228(4):391-401.[Abstract][Full Text]
43. Hatami H, Jamshidi P, Arbabi M, et al. Demographic, epidemiologic, and clinical characteristics of human monkeypox disease pre- and post-2022 outbreaks: a systematic review and meta-analysis. Biomedicines. 2023 Mar 20;11(3):957.[Abstract][Full Text]
44. Darmstadt GL, Lane AT. Impetigo: an overview. Pediatr Dermatol. 1994 Dec;11(4):293-303.[Abstract]
45. Durdu M, Baba M, Seçkin D. The value of Tzanck smear test in diagnosis of erosive, vesicular, bullous, and pustular skin lesions. J Am Acad Dermatol. 2008 Dec;59(6):958-64.[Abstract]
46. Schmidt E, Zillikens D. Modern diagnosis of autoimmune blistering skin diseases. Autoimmun Rev. 2010 Dec;10(2):84-9.[Abstract]
47. Parker SR, MacKelfresh J. Autoimmune blistering diseases in the elderly. Clin Dermatol. 2011 Jan-Feb;29(1):69-79.[Abstract]
48. Diaz LA, Giudice GJ. End of the century overview of skin blisters. Arch Dermatol. 2000 Jan;136(1):106-12.[Abstract]
49. Reina J, Saurina J, Fernandez-Baca V, et al. Evaluation of a direct immunofluorescence cytospin assay for the detection of herpes simplex virus in clinical samples. Eur J Clin Microbiol Infect Dis. 1997 Nov;16(11):851-4.[Abstract]
50. Wald A, Huang ML, Carrell D, et al. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003 Nov 1;188(9):1345-51.[Abstract][Full Text]
51. Guerry SL, Bauer HM, Klausner JD, et al. Recommendations for the selective use of herpes simplex virus type 2 serological tests. Clin Infect Dis. 2005 Jan 1;40(1):38-45.[Abstract][Full Text]
52. Dahl H, Marcoccia J, Linde A. Antigen detection: the method of choice in comparison with virus isolation and serology for laboratory diagnosis of herpes zoster in human immunodeficiency virus-infected patients. J Clin Microbiol. 1997 Feb;35(2):347-9.[Abstract][Full Text]
53. Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome). J Med Genet. 1993 Jan;30(1):53-9.[Abstract][Full Text]
54. Vyas K, Morgaonkar M, Gupta S, et al. Primary systemic amyloidosis with unusual dermatological manifestations: a rare case report. Indian J Dermatol. 2016 Mar-Apr;61(2):216-8.[Abstract][Full Text]
55. Gottlieb J, Ingen-Housz-Oro S, Alexandre M, et al. Idiopathic linear IgA bullous dermatosis: prognostic factors based on a case series of 72 adults. Br J Dermatol. 2017 Jul;177(1):212-22.[Abstract]
56. World Health Organization. Diagnostic testing for the monkeypox virus (MPXV): interim guidance. May 2024 [internet publication].[Full Text]
57. UK Health Security Agency. Mpox: diagnostic testing. Sep 2024 [internet publication].[Full Text]
58. Centers for Disease Control and Prevention. Guidelines for collecting and handling specimens for mpox testing. Sep 2024 [internet publication].[Full Text]
59. McQuiston JH, Luce R, Kazadi DM, et al. U.S. preparedness and response to increasing clade I mpox cases in the Democratic Republic of the Congo - United States, 2024. MMWR Morb Mortal Wkly Rep. 2024 May 16;73(19):435-40.[Abstract][Full Text]
60. Centers for Disease Control and Prevention. Clinical overview of mpox. Sep 2024 [internet publication].[Full Text]
