Bullous skin diseases

MOST OF BULLOUS SKIN DISEASE INCLUDED IN IT
DR MONTHER FADEL NAGI
DERMATOLOGY RESIDENT
ADEN UNIVERSITY

1. BULLOUS SKIN DISEASES Prepared By :- Dr Monther Fadel Nagi Dermatology Resident

2. Pemphigus Vulgaris

3. Pathogenesis Pemphigus vulgaris is a serious autoimmune bullous disorder caused by autoantibodies directed against desmoglein 1 and desmoglein 3 . These molecules are involved in the normal cohesion of keratinocytes , and hence, the condition leads to large flaccid bullae that are easily ruptured. The mouth is often involved. Rarely, pemphigus vulgaris is triggered by drugs or foods such as garlic and leeks .

4. Pathogenesis Drug-Induced Pemphigus • Captopril (common) • D- Penicillamine (common) • Amoxicillin (rare) • Ampicillin (rare) • Cephalosporins (rare) • Penicillin (rare) • Rifampin (rare)

5. Clinical Features • The condition typically affects older adults (40–60 years old). • Persons of Jewish or Hispanic heritage are more often affected. • The condition may be localized (often on the head or trunk), or it may eventuate as a generalized eruption. • Vesicles and bullae (up to several centimeters) arise on normal or erythematous skin

6. • The Nikolsky sign may be present . • Blisters rupture in 1 to 3 days, with a painful, raw, erythematous base. • Scaling and crusting of older lesions are common . • Oral involvement is present in more than 90% of patients during the course of the illness, and often it is the initial site of the presentation.

7. Diagnosis • A vesiculobullous disorder with marked mucosal involvement suggests the diagnosis, especially if the Nikolsky sign is present . • A shave or punch biopsy from the edge of the lesion should always be done .

8. Diagnosis • DIF using perilesional skin may be performed on a shave biopsy (preferred) or punch biopsy and submitted in immunofluorescent transport media, in saline (for up to 24–48 hours), or snap frozen . • If a direct immunofluorescent medium is not available, blood can be drawn in a red-top (serum separator) tube and sent for indirect immunofluorescent examination or ELISA testing.

9. Treatment • First-line therapy is oral prednisone (0.5–1.0 mg/ kg per day) with a slow taper, using steroid-sparing agents as the taper proceeds . • Pulse corticosteroids (250–1000 mg/day of methylprednisolone sodium succinate) for 1 to 5 days may be used for severe disease or for patients with a poor response to oral prednisone.

10. Treatment • Intravenous immunoglobulin (IVIG), 400 mg/kg per day for 5 days, with the addition of cyclophosphamide (100–150 mg/day) in severe cases, results in clearing in 80% of patients within 2 weeks . • Methotrexate, azathioprine, rituximab, and cyclophosphamide are steroid-sparing agents that may be used in select cases.

11. Linear IgA Bullous Dermatosis

12. Pathogenesis Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous condition in which IgA autoantibodies are directed against a structural component of the basement membrane zone between the epidermis and dermis . Most cases are idiopathic, but a significant number of cases are drug-induced. When it occurs in children , it has also been termed chronic bullous disease of childhood .

13. Pathogenesis Drug-Induced Linear IgA Bullous Dermatosis • Ampicillin- sulbactam (rare) • Benazepril (rare) • Carbamazepine (rare) • Ceftriaxone-metronidazole (rare) • Gemcitabine (rare) • Naproxen (rare) • Piroxicam (rare) • Sulfadimethoxine (rare) • Vancomycin (common)

14. Clinical Features • LABD may affect children and adults . • Both minute vesicles and large tense bullae may be seen, sometimes on an erythematous base. • Blisters may be arranged in groups or annular configurations , sometimes likened to a string of pearls , or with sausage or beanlike shapes.

15. Clinical Features • Lesions are often symmetrically distributed on extensor surfaces , especially the back and neck. • In severe cases , the blisters may be large and generalized, mimicking those of TEN. • Oral involvement is rather common and usually consists of oral erosions and ulcerations. • The blisters are usually pruritic .

16. Diagnosis • The clinical presentation, particularly in a child, can be persuasive, particularly because other autoimmune disorders are relatively uncommon in children . • Annular configurations of blisters, arranged as a string of pearls, strongly suggest the diagnosis. • In adults, vancomycin use should prompt consideration of drug-induced LABD .

17. Diagnosis • A shave or punch biopsy is often useful in suggesting the diagnosis, but other autoimmune blistering diseases share similar histologic features . • The diagnosis is established definitively via a punch or shave biopsy of perilesional skin for DIF studies to demonstrate a linear band of IgA autoantibodies.

18. Treatment Oral prednisone is used initially for quick control , usually at a dose of 0.5 to 1.0 mg/kg per day, with tapering as the condition improves or as steroid-sparing agents are added. • Dapsone (25–100 mg PO qd ) is the steroid-sparing drug used most often . • Sulfapyridine and colchicine are other steroid-sparing agents that are used less often.

19. Pemphigus Foliaceus

20. Pathogenesis Pemphigus foliaceus (PF) is an uncommon autoimmune bullous condition caused by immunoglobulin G ( IgG ) autoantibodies directed against desmoglein 1, a molecule involved in the normal cohesion of keratinocytes.In this condition, the split occurs below the cornified layer or in the superficial granular layer. This is the same location as the split in bullous impetigo and SSSS. PF can also be induced by some medications.

21. Pathogenesis Causes of Drug-Induced Pemphigus Foliaceus • Captopril (common) • D- Penicillamine (common) • Enalapril (rare) • Sulfasalazine (rare)

22. Clinical Features • Middle-aged and older adults are usually affected, but, on occasion, children may be affected. • There is a predilection for the head and trunk, but in some cases it may involve the entire body surface area, causing erythroderma . • Primary lesions are often ruptured vesicles or, less often, intact bullae that arise on normal or erythematous skin .

23. Clinical Features • In some cases, the blister may become cloudy or even appear pustular . • The Nikolsky sign is present in many cases . • Scaling and crusting are common , and, in some cases, the condition may resemble dermatitis . Verrucous lesions may even resemble a seborrheic keratosis. • Drug-induced PF appears clinically identical to idiopathic cases

24. Diagnosis • Recurrent, superficial, often ruptured blisters, with a background of scaling and crusting, are highly suggestive of the diagnosis . There should be no oral involvement. • It is useful to culture the blister contents to exclude bullous impetigo. • A shave or punch biopsy , performed at the edge of the lesion, is necessary to establish an acantholytic blistering disorder; this is a cardinal feature of PF .

25. Diagnosis • DIF of perilesional skin is the diagnostic method of choice. This can be performed using a shave (preferred) or punch biopsy. The tissue must be placed in immunofluorescence transport media, normal saline (for periods of <24–48 hours), or snap frozen. • If a direct immunofluorescent medium is not readily available, blood can be drawn in a red-top tube (serum separator tube) and sent to a immunofluorescence laboratory for indirect immunofluorescence or to a reference laboratory for enzyme-linked immunosorbent assay (ELISA) measurement of desmoglein antibodies.

26. Treatment • First-line therapy is oral prednisone (0.5–1.0 mg/ kg per day) with a slow taper, using steroid-sparing agents as the taper proceeds. • Other medications and/or steroid-sparing agents include methotrexate, azathioprine, dapsone , cyclophosphamide, and rituximab. • Any drug known to induce PF should be discontinued or substituted with an unrelated agent.

27. Bullous Pemphigoid

28. Pathogenesis Bullous pemphigoid (BP) is an autoimmune bullous disease that usually occurs in elderly patients, although any age group may be affected. The incidence of BP has tripled in the past 10 years as the population of the United States has aged. BP is mediated by IgG autoantibodies (BPAg1 and BPAg2) directed against portions of the hemidesmosome , a structure necessary for normal attachment of the epidermis to the dermis. This deposition results in an inflammatory milieu that causes chemotaxis of inflammatory cells, particularly eosinophils . It is unknown why these autoantibodies develop.

29. Clinical Features • Typically BP affects elderly patients, and it is more common in patients with multiple comorbidities, including neurologic disorders (e.g., dementia, Parkinson disease ). • Urticarial plaques, or tense blisters, are common Either or both forms of disease may be present in the same patient. • The Nikolsky sign is absent .

30. Clinical Features • The most common location is the lower extremity, although any skin surface may be affected. • Older lesions demonstrate a raw, denuded base. • Oral lesions are uncommon , although some studies have reported that 20% of patients have mucosal lesions .

31. Diagnosis • The occurrence of fixed urticarial lesions and tense bullae is suggestive, especially in an elderly patient . • Some bullous drug eruptions mimic BP, clinically and histologically, and a careful drug history must be taken . • A biopsy (shave, punch, or small excision) of an early urticarial lesion, or a new blister, is useful to establish the diagnosis.

32. Diagnosis • DIF is also useful to establish the diagnosis; this requires a biopsy from perilesional skin (≈0.5–1 cm away from a blister). This specimen needs to be placed in immunofluorescent transport medium, in normal saline (for 24–48 hours), or snap frozen. • DIF studies demonstrate IgG and/or complement component C3 deposited in a linear fashion at the dermoepidermal junction. • Indirect immunofluorescent studies have lesser sensitivity (positive in 50%–80% of patients).

33. Treatment • Those with a mild case and/or localized disease may be managed with potent topical corticosteroids . • Moderate to severe cases are managed first with oral prednisone (≥0.5 mg/kg per day) , with the understanding that many elderly patients have comorbidities (e.g., diabetes) that may complicate Use.

34. Treatment • After controlling the disease with oral corticosteroids, steroid-sparing agents are generally used. These may include doxycycline (100 mg PO bid) with nicotinamide (500 mg PO qid ), dapsone (typical starting dose, 50 mg/day), and methotrexate (5–15 mg as a weekly dose). • Treatments used less often include azathioprine, cyclophosphamide, mycophenolate , methotrexate, chlorambucil , plasmapheresis , IV gamma globulin, and rituximab.

35. Bullous Insect and Arthropod Reactions

36. Pathogenesis Insects and arthropods can produce hypersensitivity reactions in the skin . Saliva from the bite of the organism (e.g., bedbugs, ticks) or feces (e.g., scybala of scabies) may serve as an allergen. When allergen exposure is limited, the host response is usually minor. However, when the antigen exposure is more substantial, or the host response is exaggerated, a vesiculobullous reaction can ensue. Common causes of bullous arthropod reactions include bedbugs ( Cimexlectularius ), fleas , and chiggers.

37. Clinical Features • Patients may or may not recall the insect or arthropod bite . • Lesions are often located on exposed areas of the body and range from urticarial papules to bullae . • Lesions may be solitary or multiple, and lesions can be grouped, especially in bedbug bites. • The blister may be unilocular or multilocular on an erythematous base .

38. Clinical Features • Bedbug bites occur most often on parts of the body exposed during sleep (face, neck, hands, and arms), and bites are often arranged in linear configurations (so-called breakfast, lunch, and dinner arrangement). • Bullous insect and arthropod bite reactions are nearly always intensely pruritic, except for blistering reactions caused by cutaneous exposure to members of the blister beetle family.

39. Diagnosis • In some cases, the patient may bring in the offending insect or arthropod . • Bedbugs are a particular problem of travelers, and a travel history should be elicited .

40. Diagnosis • According to a major national extermination company, the top 10 cities for bedbugs includes Detroit, Philadelphia, Cleveland, Los Angeles, Dayton, Chicago, Columbus, Cincinnati, Dallas– Fort Worth, and San Francisco. • A shave or punch biopsy is not usually indicated but, in problematic cases, the findings in a biopsy can be supportive of the diagnosis.

41. Treatment • Sedating antihistamines (e.g., diphenhydramine) may be used at night for symptomatic relief and to promote sleep. • Potent or ultrapotent forms may be used in a directed manner for a limited duration. • Oral antibiotics may be appropriate if a secondary bacterial infection is suspected. • Depending on the clinical situation, other treatments might include repellants, removal of pets or wildlife (e.g., an abandoned bird’s nest near a bedroom window), and/or professional extermination.

42. Blistering Distal Dactylitis

43. Introduction Blistering distal dactylitis is an uncommon bacterial infection that causes superficial blisters on the distal fingers of young children. In reality, it is simply bullous impetigo of acral skin; however, because of the thick stratum corneum on the hands, the blisters are tense. It is a distinctive disorder that presents in acute fashion. It is caused most often by β-hemolytic strains of Streptococcus pyogene s and less often by S. aureus .

44. Clinical Features • Characteristically, the condition affects children and, less often, adolescents. Adults are rarely affected, with most adult cases occurring in those who are immunocompromised . • Occasionally, classic impetigo may also be present elsewhere .

45. Clinical Features • The disorder yields rapidly evolving tense and painful bullae on the anterior fat pads of the distal fingertips . Older lesions may become crusted . • Less often, the bullae extend to involve the lateral and proximal nail folds.

46. Diagnosis • The clinical presentation is suggestive of blistering distal dactylitis , but the differential diagnosis includes traumatic blisters, thermal and chemical burns , and herpetic whitlow (herpes simplex infection of the finger ). •The blisters of distal dactylitis are typically unilocular ,

47. Diagnosis whereas the blisters of herpetic whitlow are usually multilocular ; this is an important diagnostic clue. • In an urgent care or office setting, the blisters can be aspirated, with Gram staining performed on the fluid and with abundant gram-positive cocci apparent. • The aspirate can be cultured with antibiotic sensitivities used to guide management.

48. Treatment • Tense blisters may be drained , but there is no evidence that this speeds recovery. • Dicloxacillin at a dose of 3.125 to 6.25 mg/kg may be used for children weighing less than 40 kg. • Alternative treatments include cephalexin, erythromycin, or another oral antibiotic that covers streptococcal and staphylococcal infection . • Because of the thickness of the blister roof and frequent presence of β-hemolytic strains of S. pyogenes , topical antibiotics, at least as solo therapy, are not recommended .

49. Staphylococcal Scalded Skin Syndrome (SSSS)

50. Pathogenesis Staphylococcal scalded skin syndrome (Ritter; SSSS) is caused by infection with group II (often phage group 71) S. aureus . Blisters are caused by exfoliative toxins elaborated by the bacteria that lyse an attachment molecule ( desmoglein 1) located between keratinocytes . The result is a superficial split in the epidermis in the area of the granular layer. It is thought that infants and young children are more susceptible because immature kidney function does not clear the toxins. This is the same reason why an increased incidence of SSSS is observed in adults with renal disease. Increased susceptibility in immunocompromised adults is poorly understood but may be due to impaired neutralization of the toxin.

51. Pathogenesis Nikolsky Sign The Nikolsky sign refers to the production or extension of a blister by lateral or rotating pressure on the epidermis with a finger or a pencil. It is usually associated with the following diseases : • Pemphigus vulgaris • Staphylococcal scalded skin syndrome • Toxic epidermal necrolysis

52. Clinical Features • The condition occurs most often in neonates and young children (<5 years). • The primary site of infection is often unapparent but a prodrome of fever, malaise, lethargy, and irritability is often observed. • In children and neonates, the disease often begins in the perioral region and on the neck, axillae , and groin . • Early lesions are tender and erythematous and manifest variable edema, with superficial bullae and skin fissuring.

53. Clinical Features • Blisters are fragile, and sloughing leaves shallow bullae, with a moist erythematous surface • The Nikolsky sign is often present . • Adults who experience SSSS frequently have impaired renal function or are immunocompromised and may also develop a staphylococcal cellulitis. • Mucosal sites are rarely involved .

54. Diagnosis • The clinical presentation is usually diagnostic in neonates, infants, and children . • Because the process is caused by a systemic toxin, Gram staining and cultures of blister cavity fluid are negative, in contrast to bullous impetigo. • The diagnosis may be suggested on biopsy, with a cleavage plane immediately below the granular layer, but a biopsy is not usually required. The histologic findings of pemphigus foliaceus overlap.

55. Treatment • Older infants and young children who are able to eat and drink, and who are with limited cutaneous disease, can be treated with oral antibiotics sufficient to cover S. aureus and with local skin care. • Neonates and children with more severe disease may require admission for intravenous antistaphylococcal antibiotics such as naficillin , oxacillin , vancomycin , or linezolid . • Bland emollients (white petrolatum) may be used to decrease pain and promote re-epithelialization. • NSAIDs and other drugs that impair renal function should be avoided .

56. Bullous Fixed Drug Eruption

57. Pathogenesis Fixed drug eruptions (FDEs) are reactions produced by drugs—and rarely by foods—that are localized (fixed) to one or more mucocutaneous sites . More than 100 drugs have been documented to produce this reaction (see box). The pathogenesis of FDE remains unknown, but studies have suggested that T and B cells are stimulated by the causative drug, and skin damage is due to antibody-dependent cell cytotoxicity.

58. Pathogenesis Common Causes of Fixed Drug Eruption • Acetaminophen • Antimalarials • Barbiturates • Fluoroquinolones • Nonsteroidal antiinflammatory drug (NSAIDs) • Penicillins • Phenolphthalein • Tetracyclines (class effect) • Trimethoprim- sulfamethoxazole

59. Clinical Features • An initial episode occurs 1 to 2 weeks after drug exposure , but subsequent exposures can trigger an effect within hours . • Usually, only one site is affected in a first episode, but subsequent episodes can involve the initial site and one or more additional sites.

60. Clinical Features • The primary lesion is an erythematous macule that rapidly becomes an erythematous plaque . • The erythema may subside or the lesion may become bullous or ulcerated . • The lesion resolves with residual hyperpigmentation . • The face and male genitalia are the sites affected most often.

61. Diagnosis • The diagnosis is usually established on clinical grounds , with the presentation of one or more discrete bullous lesions, following ingestion of a drug . The diagnosis is further established if a history reveals that this same site has been involved in other reactions precipitated by the same drug. • Rare cases may require a drug challenge or a 3- or 4-mm punch biopsy. The histologic findings are not usually specific for only FDE but can strongly suggest the diagnosis. • Because FDE is common on the male genitalia, and doxycycline is a drug used for a variety of sexually transmitted diseases but can cause FDE, it is often important to establish precisely when an ulceration of the penis began relative to the use of doxycycline.

62. Treatment • The implicated drug needs to be discontinued immediately because the lesions will typically progress to ulceration if the drug continues to be administered. • Topical corticosteroids , when applied early in the course of the reaction, will shorten the duration of the inflammatory phase. The strength of the steroid should be adjusted to the affected skin.

63. Stevens-Johnson Syndrome

64. Pathogenesis Stevens-Johnson syndrome (SJS), sometimes referred to as erythema multiforme major, is a hypersensitivity process usually caused by drugs, including antiepileptics , antibiotics, and NSAIDs, and sometimes by infections (e.g., HSV, Mycoplasma ). The precise nosology of SJS is controversial, with some authorities considering it a disorder sui generis and others considering it on a spectrum with toxic epidermal necrolysis (TEN). This latter viewpoint has prevailed in recent years. Classic SJS is defined as a vesiculobullous disorder with targetoid lesions that affects at least two mucosal surfaces.

65. Clinical Features • SJS may affect persons of any age. • Clinical lesions develop about 1 to 3 weeks after ingestion of a causative drug or after a causative infection, although sometimes SJS may occur within a few days if it is a recurrent episode. • Patients often demonstrate a prodrome of fever, malaise, and myalgias . • Cutaneous lesions resemble targetoid lesions of erythema multiforme minor and may become bullous .

66. Clinical Features • Lesions may involve the following: – <10% of body surface area—considered classic SJS – 10% to 30% of body surface area—considered SJS-TEN overlap – >30% body surface area—often considered simply as TEN • Lesions are often painful and/or may produce a burning sensation. • Older bullous lesions may rupture or collapse, with the epidermis shed, yielding superficial ulcers. • The ocular mucosa, lips, oral mucosa , anogenital mucosa , and lung mucosa • Lesions may occur in sites of trauma ( Koebner or isomorphic phenomena).

67. Diagnosis • The classic presentation of admixed bullous lesions, atypical bullous targetoid lesions, and involvement of at least two mucosal surfaces is sufficient for establishing the diagnosis. • A history of new medications within the past 3 weeks, or an infection, especially with Mycoplasma, supports the diagnosis. • Biopsies should be performed for standard H&E examination and for DIF studies to exclude autoimmune bullous conditions that can mimic SJS (e.g., paraneoplastic pemphigus).

68. Treatment • All patients should be hospitalized for supportive therapy to include IV hydration, a controlled diet, thermoregulation, pain control, and mouth rinses and emollients. • Potentially causative drugs must be discontinued as soon as possible. • Cases associated with possible recurrent HSV infection may be treated with antivirals; cases of suspected Mycoplasma pneumonia should be treated with antibiotics. • Use of oral corticosteroids in bullous erythema multiforme is controversial, but most evidence suggests that high-dose, short-duration steroid regimens may be used early in the disease course.

69. Toxic Epidermal Necrolysis

70. Pathogenesis TEN is a life-threatening, severe hypersensitivity reaction to a drug (most common), infection or, rarely, an immunization and represents a dermatologic emergency.Many authorities consider it to be a severe variant of Stevens-Johnson syndrome (see previous section). For some drugs, there is evidence of a genetic predisposition to develop TEN.

71. Pathogenesis Common Causes of Toxic Epidermal Necrolysis • Drugs • Allopurinol • Barbiturates • Hydantoin • NSAIDs • Penicillins • Sulfonamides • Immunizations • Infections • Herpes simplex • Mycoplasma • Systemic fungal infections

72. Clinical Features • TEN may affect any age group. • Lesions develop about 1 to 3 weeks after a causative drug (or infection), but some drug-induced cases may develop quickly . • Patients typically complain of skin pain and/or skin burning and may develop erythema of the skin, which rapidly becomes confluent, resembling a sunburn.

73. Clinical Features • By definition (, “Stevens-Johnson Syndrome”), from 30% to 100% of the skin surface is involved . • Fully developed lesions consist of sheets of necrotic epidermis that shear easily, leaving an erythematous raw base. • The Nikolsky sign may be present, where the skin will denude with lateral pressure. • The ocular mucosa, lips, oral mucosa, anogenital mucosa, and sinopulmonary epithelium may be involved.

74. Diagnosis • The classic presentation of painful erythema, resembling severe sunburn, that easily denudes and occurs after ingestion of a new medication, is strongly suggestive of the diagnosis. • A positive Nikolsky sign is also strongly supportive of the diagnosis . • All cases should be biopsied for H&E and direct immunofluorescence because this clinical pattern maybe mimicked by other severe bullous disorders, such as pemphigus, paraneoplastic pemphigus, and drug-induced, linear, IgA bullous dermatosis . • All patients should have a complete blood count (CBC ) and comprehensive metabolic panels ( to include kidney and liver function).

75. Treatment • All patients should be hospitalized, preferably in a burn unit, for supportive therapy . This should include proper hydration, a controlled diet, thermoregulation, mouth rinses, eye care, analgesics, and emollients. • Immediately withdraw any potentially causative drugs . • As the skin denudes, replacement with some form of appropriate dressing should be considered. • Prophylactic antibiotics are not used, but the threshold for culture and starting antibiotics is low. • Second-line and controversial therapies include IVIG , cyclosporine, plasmapheresis , and systemic corticosteroids . • There should be liberal ophthalmology consultation for patients with any possible ocular involvement.

76. Hand, Foot, and Mouth Disease .

77. Pathogenesis Hand, foot, and mouth disease (HFMD) is an infection caused chiefly by coxsackievirus group A viruses, with the most common cause being A16. Less often, the disease may be caused by coxsackievirus groups A4, A5, A6, A7, A9, and A10, coxsackievirus groups B1, B2, B3, and B5, or enterovirus 71. Transmission is fecal-oral. HFMD tends to occur in miniepidemics during the summer months.

78. Clinical Features • Typically, young children are affected, but the virus may also affect adolescents and adults on occasion. • The incubation period is brief (3–6 days). • A brief prodrome of low-grade fever, malaise, anorexia, and abdominal pain may be present. • Primary lesions are round to oval erythematous papules, with central vesicles and a cloudy or opalescent appearance. • Lesions arise most often on the hands and feet . At other anatomic sites, the primary lesions may simply be red macules, with variable scale or crust.

79. Clinical Features • The number of lesions varies widely, from only a few to over 100. • Although the hands and feet are most often involved, other common sites include the anogenital area , buttocks, and flexural areas . • An enanthem may affect the buccal mucosa, tongue, soft palate, or gingiva and is seen in about 90% of patients as round to oval erosions on an erythematous base, which can be painful • One or more nails can be shed ( onychomadesis ). • Lymphadenopathy is present in about 20% of cases . • Lesions resolve without scarring .

80. Diagnosis • The clinical presentation of a young child (usually <4 years old) with low-grade fever and lesions on the hands, feet, and oral mucosa is usually sufficient for a presumptive diagnosis. • Problematic or severe cases may be diagnosed with viral cultures of the oral pharynx or the fluid aspirated from vesicles. Material from these same sites can also be tested by PCR-based modalities.

81. Treatment • The disease is self-limited and only symptomatic, and supportive treatments are used. There is no specific antiviral therapy.

82. THANK YOU DR MONTHER FADEL NAGI DERMATOLOGY RESIDENT