Autoimmune bullous dermatoses


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Autoimmune bullous dermatoses

  1. 1. Autoimmune Bullous Dermatoses:Pemphigus
  2. 2. MeSH D010392
  3. 3. Microscopic image of direct immunofluorescenceusing an anti-IgG antibody. The tissue is skin from apatient with Pemphigus vulgaris. Note theintercellular IgG deposits in the epidermis and theearly intraepidermal vesicle caused by acantholysis.Pemphigus ( /ˈpɛmfɪɡəs/ or /pɛmˈfaɪɡəs/) is a raregroup of blistering autoimmune diseases that affectthe skin and mucous membranes.[1]In pemphigus, autoantibodies form againstdesmoglein. Desmoglein forms the "glue" thatattaches adjacent epidermal cells via attachment
  4. 4. points called desmosomes. When autoantibodiesattack desmogleins, the cells become separated fromeach other and the epidermis becomes "unglued", aphenomenon called acantholysis. This causes blistersthat slough off and turn into sores. In some cases,these blisters can cover a significant area of the skin.[2]Originally, the cause of this disease was unknown,and "pemphigus" was used to refer to any blisteringdisease of the skin and mucosa. In 1964, a historicpaper that changed the understanding of pemphigus
  5. 5. was published.[3][4]In 1971, an article investigating theautoimmune nature of this disease was published.[5][6]Contents• 1 Types• 2 Classification• 3 Diagnosis• 4 Treatment•Types
  6. 6. There are three types of pemphiguswhich vary in severity: pemphigusvulgaris, pemphigus foliaceus, andparaneoplastic pemphigus.• The most common form of thedisorder is pemphigus vulgaris (Itoccurs when antibodies attack
  7. 7. Desmoglein 3. Sores oftenoriginate in the mouth, makingeating difficult and uncomfortable.Although pemphigus vulgaris mayoccur at any age, it is mostcommon among people betweenthe ages of 40 and 60. It is more
  8. 8. frequent among Ashkenazi Jews.Rarely, it is associated withmyasthenia gravis. Nail diseasemay be the only finding and hasprognostic value in management.• Pemphigus foliaceus (PF) is theleast severe of the three varieties.
  9. 9. Desmoglein 1, the protein that isdestroyed by the autoantibody, isonly found in the top dry layer ofthe skin. PF is characterized bycrusty sores that often begin on thescalp, and may move to the chest,back, and face. Mouth sores do not
  10. 10. occur. It is not as painful aspemphigus vulgaris, and is oftenmis-diagnosed as dermatitis oreczema.• The least common and mostsevere type of pemphigus isparaneoplastic pemphigus
  11. 11. (PNP). This disorder is acomplication of cancer, usuallylymphoma and Castlemansdisease. It may precede thediagnosis of the tumor. Painfulsores appear on the mouth, lips,and the esophagus. In this variety
  12. 12. of pemphigus, the disease processoften involves the lungs, causingbronchiolitis obliterans(constrictive bronchiolitis).Complete removal and/or cure ofthe tumor may improve the skin
  13. 13. disease, but lung damage isgenerally irreversible .Note that Hailey-Hailey disease,also called familial benignpemphigus, is an inherited(genetic) skin disease, not anautoimmune disease. It is therefore
  14. 14. not considered part of thePemphigus group of diseases.[7]ClassificationPemphigus is a group ofautoimmune blistering diseases thatmay be classified into the followingtypes[8]:
  15. 15. • Pemphigus vulgaris, of whichthere several forms:• Pemphigus vegetans• Pemphigus vegetans ofHallopeau• Pemphigus vegetans of Neumann
  16. 16. • Pemphigus foliaceus, of whichthere several forms:• Pemphigus erythematosus• Endemic pemphigus• Paraneoplastic pemphigus• IgA pemphigus, of which thereseveral forms:
  17. 17. • Subcorneal pustular dermatosis• Intraepidermal neutrophilic IgAdermatosisDiagnosisPemphigus is recognized by adermatologist from the appearanceand distribution of the skin lesions.
  18. 18. It is also commonly diagnosed byspecialists practicingotolaryngology- head and necksurgery, periodontists, oral andmaxillofacial surgeons (specialistsqualified in both medicine anddentistry) and eye doctors as lesions
  19. 19. can affect the eyes and mucousmembrane of the oral cavity.Intraorally it resembles the morecommon diseases lichen planus andmucous membrane pemphigoid.[9]Definitive diagnosis requiresexamination of a skin or mucous
  20. 20. membrane biopsy by adermatopathologist or oralpathologist. The skin biopsy istaken from the edge of a blister,prepared for histopathology andexamined with a microscope. Thepathologist looks for an
  21. 21. intraepidermal vesicle caused bythe breaking apart of epidermalcells (acantholysis). Thus, thesuperficial (upper) portion of theepidermis sloughs off, leaving thebottom layer of cells on the "floor"of the blister. This bottom layer of
  22. 22. cells is said to have a "tombstoneappearance".Definitive diagnosis also requiresthe demonstration of anti-desmoglein autoantibodies by directimmunofluorescence on the skinbiopsy. These antibodies appear as
  23. 23. IgG deposits along the desmosomesbetween epidermal cells, a patternreminiscent of chicken wire. Anti-desmoglein antibodies can also bedetected in a blood sample usingthe ELISA technique. A high titreof cANCA is claimed to be an
  24. 24. important feature of the disease onseveral WWW pages, but is notmentioned in current Dermatologytextbooks nor do the terms"Pemphigus" and "cANCA"produce any hits on a PUBMEDsearch.[citation needed]
  25. 25. Half of pemphigus patients haveoral lesions alone during the firstyear but develop skin lesions later.TreatmentIf not treated, pemphigus can befatal from an overwhelminginfection of the sores. The most
  26. 26. common treatment is theadministration of oral steroids,especially prednisone, and often inhigh doses. The side effects ofcortico-steroids may require the useof so-called steroid-sparing oradjuvant drugs. The immuno-
  27. 27. suppressant CellCept(Mycophenolic acid) is amongthose being used.[10]Intravenous gamma globulin (IVIG)may be useful in severe cases,especially paraneoplasticpemphigus. Mild cases sometimes
  28. 28. respond to the application of topicalsteroids. Recently, Rituximab, ananti-CD20 antibody, was found toimprove otherwise untreatablesevere cases of Pemphigus vulgaris.[11][12]
  29. 29. All of these drugs may cause severeside effects, so the patient should beclosely monitored by doctors. Oncethe outbreaks are under control,dosage is often reduced, to lessenside effects.
  30. 30. If paraneoplastic pemphigus isdiagnosed with pulmonary disease,a powerful cocktail of immunesuppressant drugs is sometimesused in an attempt to halt the rapidprogression of bronchiolitisobliterans, including
  31. 31. methylprednisolone, ciclosporin,azathioprine and thalidomide.Plasmapheresis may also be useful.If skin lesions do become infected,antibiotic may be prescribed.Tetracycline antibiotics have amildly beneficial effect on the
  32. 32. disease, and are sometimes enoughfor Pemphigus Foliaceus. Inaddition, talcum powder is helpfulto prevent oozing sores fromadhering to bedsheets and clothes.Pain is a common part of thedisease. Only one literature review
  33. 33. on peer-reviewed articles reportingpemphigous pain management hasbeen published inPemphigus vulgarisParaneoplastic pemphigusBullous pemphigoid
  34. 34. Cicatricial pemphigoidDermatitis herpetiformisPemphigus VulgarisPemphigus encompasses a group ofauto-immune blistering diseases of
  35. 35. the skin and mucous membranes.Included in this group is pemphigusvulgaris, a bullous diseaseinvolving the skin and mucousmembranes, which may be fatal ifnot treated with appropriateimmunosuppressive agents. The
  36. 36. detection of circulating antibodiesagainst keratinocyte cell surfacesled to the understanding thatpemphigus was an autoimmunedisease.According to several retrospectivestudies,2 the prevalence of
  37. 37. pemphigus vulgaris is equal in menand women. Although it may beseen in children and the elderly, themean age of onset is between 40and 60 years. Pemphigus vulgaris isalso more common in persons ofJewish and Mediterranean descent.
  38. 38. Characteristically, lesions start inthe oral mucosa, followed by theappearance of skin lesions monthslater. The bullae on the skin mayremain localized for six to 12months, then subsequently becomewidespread. Rarely, the lesions may
  39. 39. arise as a generalized acuteeruption. The lesions can be pruriticbut are usually painful andaccompanied by a burningsensation. Mouth lesions may betender, preventing adequate foodintake that leads to weight loss. The
  40. 40. lesions may be accompanied byweakness and malaise, and a historyof epistaxis, dysphagia, andhoarseness.The primary lesion on the skin is aflaccid blister. These blisters arefragile, rupture easily and,
  41. 41. therefore, are not often seen. Morelikely to be noticed are the painfulerosions that are the result ofbroken blisters (Figure 1). Theseerosions bleed easily and oftenbecome crusted. The lesions areround to oval in shape, and range
  42. 42. from skin-colored to erythematous.Nikolskys sign, in which theepidermis is easily detached fromthe skin, is elicited by applyinglateral pressure to a bulla, leading tolateral extension of the blister, andis usually positive. Sites of
  43. 43. predilection include the scalp, face,chest, axillae, groin, and umbilicus.
  44. 44. FIGURE 1.
  45. 45. Pemphigus vulgaris. Erosions andflaccid bullae on normal skin.Painful erosions, most often in theoral cavity, are seen in nearly allpatients with pemphigus vulgaris(Figure 2). The buccal mucosa isthe most common site of
  46. 46. involvement in the oral cavity.Other sites of mucous membraneinvolvement include the pharynxand larynx, which is manifested byhoarseness. The conjunctiva,esophagus, anus, penis, vagina, andlabia have also been reported as
  47. 47. sites where painful erosions arelocated.
  48. 48. FIGURE 2.
  49. 49. Pemphigus vulgaris. Involvementof the oral mucosal membranes.Biopsy of the margin of a bulla,when examined by lightmicroscopy, will reveal asuprabasilar blister withacantholysis. The acantholysis is
  50. 50. caused by a loss of cohesionbetween cells in the lowerepidermis, resulting in theformation of a blister just above thebasal cell layer. Early pemphigusvulgaris lesions may showeosinophilic spongiosis as well.
  51. 51. Intercellular deposits of IgG and C3are the defining signs of pemphigusvulgaris. Thus, there is intercellularstaining throughout the epidermison direct immunofluorescence.TREATMENT
  52. 52. Corticosteroids are the mainstay oftreatment for patients withpemphigus vulgaris. Prednisone (1mg per kg per day), with or withoutother immunosuppressive agents,should be initiated immediately. Itshould be continued until there is
  53. 53. cessation of new bullae formationand Nikolskys sign can no longerbe elicited. The dosage is thenreduced by one half until all of thelesions have cleared, followed bytapering to a minimum effectivemaintenance dosage.
  54. 54. Other immunosuppressive agentsused in conjunction withcorticosteroids include azathioprine(Imuran), methotrexate,cyclophosphamide (Cytoxan), andmycophenolate mofetil (CellCept).Because it may take several weeks
  55. 55. for the immunosuppressive agentsto work, some physicians start theseagents concurrently withprednisone. In severe cases,plasmapheresis may be required.COURSE ANDCOMPLICATIONS
  56. 56. Even with the use of corticosteroidsand other immunosuppressiveagents, there is still significantmorbidity and mortality associatedwith pemphigus vulgaris. Acommon cause of death is infectionsecondary to the
  57. 57. immunosuppression required totreat the disease. Most deaths occurwithin the first few years of thedisease.2 Unfortunately, many ofthe drugs used to treat this diseasehave serious side effects, andpatients must be monitored closely
  58. 58. for infection, renal and liverfunction abnormalities, electrolytedisturbances, hypertension,diabetes, anemia, andgastrointestinal bleeding.
  59. 59. Paraneoplastic PemphigusParaneoplastic pemphigus is anextremely rare entity that has anonset at 60 years or older and ismore common in women than men.It is distinct from the classic formsof pemphigus and is characterized
  60. 60. by extensive mucocutaneouserosions in the presence of aneoplasm, most often a leukemia ora lymphoma.3 Other associatedneoplasms, malignant and benign,include Waldenströmsmacroglobulinemia, sarcomas,
  61. 61. thymomas, and Castlemansdisease.4The predominant feature ofparaneoplastic pemphigus is painfulmucous membrane erosions, ofwhich oral erosions are the firstsign of disease in 22.2 percent of
  62. 62. cases.5 The most common sitesinvolved are the lips and oralmucosa, with multiple, severe,persistent erosions. Symptoms oforopharyngeal involvement mayinclude sore throat and dysphagia.Bilateral conjunctival involvement
  63. 63. has been noted in up to 72.2 percentof cases.5 The skin lesions vary inshape and size, with a confluenterythema of the trunk, on whichblisters and erosions form.Erythematous maculopapularlesions with dusky centers or
  64. 64. central vesicles may arise on theextremities, mimicking targetlesions seen in erythemamultiforme. Occasionally, thelesions may be pruritic.On histopathologic examination,paraneoplastic pemphigus appears
  65. 65. to be a combination of pemphigusvulgaris and erythema multiforme.There is suprabasilar acantholysisas seen in pemphigus vulgaris, aswell as basal cell vacuolation,lymphocytic exocytosis, and
  66. 66. dyskeratotic keratinocytes typical oferythema multiforme.Paraneoplastic pemphigus isdistinguished from the other formsof pemphigus as directimmunofluorescence reveals notonly IgG and C3 deposits within the
  67. 67. intercellular spaces but also alongthe basement membrane zone.In the classic forms of pemphigus,indirect immunofluorescence ispositive only on stratified squamousepithelial substrates. However, inparaneoplastic pemphigus, there is
  68. 68. staining of other tissues, includingthe bladder, heart, and liver. IgGautoantibodies are directed againstdesmoplakins I and II (componentsof the cytoplasmic plaque), whichare present in stratified squamousepithelium and these other tissues.
  69. 69. TREATMENTThere is little to offer in thetreatment of paraneoplasticpemphigus. If a benign tumor isresected, some patients may go intoremission. Unfortunately, theprognosis is generally poor, and
  70. 70. treatment is usually unsuccessful.Immunosuppressive treatment andplasmapheresis have not beeneffective; however,immunophoresis may be apromising alternative.6
  71. 71. COURSE ANDCOMPLICATIONSParaneoplastic pemphigus is arapidly progressive bullous diseasethat is invariably fatal whenassociated with a malignant tumor.When paraneoplastic pemphigus
  72. 72. occurs in the context of a benignneoplasm, the mucocutaneouserosions will usually show gradualresolution after excision of thetumor. It is important to rememberthat paraneoplastic pemphigus mayprecede the clinical appearance of a
  73. 73. neoplasm; therefore, it is mandatorythat these patients receive screeningfor neoplasms and regular follow-up care.Bullous PemphigoidBullous pemphigoid is anautoimmune skin disorder
  74. 74. characterized by subepidermalblistering that results in large, tensebullae. It occurs mainly in theelderly and rarely in children. Onsetis typically between 60 and 80years of age. There is equalincidence in men and women, and
  75. 75. there are no known racial or ethnicpredilections. In France andGermany, the incidence is estimatedat seven per 1 million per year.7The lesions of bullous pemphigoidmay initially start as an urticarialeruption (Figure 3), which over a
  76. 76. course of weeks to months,develops into bullae. The lesionsare usually pruritic, and there maybe tenderness at the site of erodedlesions.
  77. 77. FIGURE 3.Bullous pemphigoid. Urticarialplaques.
  78. 78. Once formed, blisters are large andtense, with a round or oval shape.Discrete lesions arise on normal orerythematous skin (Figure 4) andare scattered throughout the body,including the axillae, medial thighs,groin, abdomen, flexor forearms,
  79. 79. and lower legs. The lesions may belocalized or generalized. Mostoften, the bullae are filled with aclear fluid, but they also can behemorrhagic. There is no scarformation noted following thelesions of bullous pemphigoid, but
  80. 80. milia may appear at sites ofpreviously involved skin.
  81. 81. FIGURE 4.Bullous pemphigoid. Tense bullaeon erythematous skin.The involvement of mucousmembranes is much less commonwith bullous pemphigoid than inpemphigus vulgaris, with blisters
  82. 82. that are less easily ruptured. Sitesinvolved include the oral cavity,anus, and genital mucosa.Histologic examination of a skinbiopsy from a bulla reveals asubepidermal blister withsuperficial dermal inflammation
  83. 83. consisting of lymphocytes,histiocytes, and eosinophils.Urticarial lesions may also beaccompanied by papillary dermaledema.On electron microscopy, blisterformation is found to occur within
  84. 84. the lamina lucida of the basementmembrane, causing a loss ofanchoring filaments andhemidesmosomes. Directimmunofluorescence revealsdeposition of IgG, and possibly C3,
  85. 85. along the basement membrane zonein a linear pattern.TREATMENTTreatment consists of systemicprednisone, alone or in combinationwith a steroid-sparing agent such asazathioprine, mycophenolate
  86. 86. mofetil or a tetracycline. Thesedrugs are usually startedsimultaneously, followed by agradual tapering of the prednisoneand continuation of the steroid-sparing agent until clinicalremission is achieved. Mild cases
  87. 87. may require only topicalcorticosteroids. Methotrexate maybe used in patients with severedisease who are unable to tolerateprednisone.COURSE ANDCOMPLICATIONS
  88. 88. Bullous pemphigus is a self-limiteddisease, but may last from monthsto years. It is rarely fatal, and evenwithout corticosteroid therapy,carries a good prognosis.Approximately one half of treatedcases will remit within six years.7
  89. 89. Cicatricial PemphigoidCicatricial pemphigoid is a rare,blistering disease of the skin,characterized by severe, erosivelesions of the skin and mucousmembranes. Mucous membraneinvolvement is common, primarily
  90. 90. of the oral mucosa and conjunctiva,but may also include thenasopharynx, larynx, esophagus,genitalia, and rectal mucosa. Skininvolvement occurs in one third ofpatients and is focused around thescalp, face, and upper trunk, and
  91. 91. heals with scars. The bullae aretense, and located on anerythematous or urticarial base(Figure 5). The vesiculobullouslesions tend to rupture within hours,leaving painful erosions and ulcersthat can easily become secondarily
  92. 92. infected. Ocular cicatricialpemphigoid is characterized bychronic conjunctivitis that leads todecreased vision, photosensitivity,and scarring and fibrosis that caneventually cause blindness (Figure6).
  93. 93. FIGURE 5.
  94. 94. Cicatricial pemphigoid. Tensebullae on erythematous skin.
  95. 95. FIGURE 6.
  96. 96. Cicatricial pemphigoid. Symble-pharon formation.There is a 2:1 preponderance forwomen, and the age of onset istypically in late adulthood, mostoften between 40 and 60 years ofage.7
  97. 97. Lesions of the oral mucosa may beseen on the gingiva, buccal mucosa,palate, tongue, and lips. The lesionsconsist of tense blisters that ruptureeasily and erosions. In severe casesof cicatricial pemphigoid, there maybe adhesions between the various
  98. 98. structures of the oral cavityinvolved, and gingival involvementcan cause dental complications.Other mucous membranes that canbe affected include those of thenasopharynx, larynx, andesophagus. Laryngeal involvement
  99. 99. may lead to a sore throat,hoarseness, and possible loss ofspeech. Supraglottic stenosissecondary to erosions, scarring, andedema may necessitate atracheostomy as the airway isfurther compromised. Esophageal
  100. 100. erosions and scarring, which occursin 8 percent of cases,8 can lead tothe formation of strictures, andthese patients may present withdysphagia, odynophagia, andweight loss. Eventually, complete
  101. 101. occlusion of the esophagus mayoccur.The blisters are subepidermal andsurrounded by a mixedinflammatory cell infiltrate. Inmucosal lesions, this infiltrate isprimarily made up of mononuclear
  102. 102. cells, histiocytes and plasma cells,while the skin lesion infiltrate iscomposed predominantly ofeosinophils and neutrophils. Olderskin lesions have less inflammation,with prominent fibroblastproliferation.
  103. 103. Direct immunofluorescence revealslinear deposition of C3 and IgGcontinuously along the basementmembrane. IgA and IgM may alsobe detected. These findings areobserved in unaffected andperilesional skin.
  104. 104. TREATMENTTreatment of mild lesions of theskin and oral mucosa consists oftopical corticosteroids in a gel orocclusive base, which is best usedbefore bedtime. A swish and spitdexamethasone (Roxane)
  105. 105. mouthwash can be helpful for orallesions. Dapsone has been shown tobe of benefit in some cases. Insevere cases of cicatricialpemphigoid, systemic steroids areprescribed, with or withoutdapsone. Because of the severity of
  106. 106. the sequelae of these lesions,aggressive early treatment isessential. For severe ocularinvolvement, patients are treatedwith systemic steroids, along withcyclophosphamide or azathioprine.Prednisone is usually given for
  107. 107. three to six months, with thecyclophosphamide or azathioprinecontinued for one year. At thatpoint, the medications may bedecreased, and if the patientremains free of disease, themedications may be discontinued.
  108. 108. COURSE ANDCOMPLICATIONSCicatricial pemphigoid is a chronicprogressive disease that rarelyremits spontaneously. Earlyimmunosuppressive treatment isnecessary. All patients will need
  109. 109. thorough ophthalmologic anddermatologic examinations, andconsultations with otolaryngology,gastroenterology, and gynecologyspecialists may also be appropriate.Dermatitis Herpetiformis
  110. 110. Dermatitis herpetiformis is anintensely pruritic, chronic skindisease characterized bypapulovesicular lesions andurticarial wheals located on theextensor surfaces in a symmetricdistribution. The disease persists
  111. 111. indefinitely, and is associated witha gluten-sensitive enteropathy inmost patients.The incidence of dermatitisherpetiformis is 10 to 39 cases per100,000 persons. Onset tends to bebetween 20 and 40 years of age but
  112. 112. may occur at any age, includingchildhood, and there is a 2:1preponderance for men.7 Dermatitisherpetiformis is principally adisease that affects whites. It rarelyoccurs in blacks or Asians.
  113. 113. The lesions of dermatitisherpetiformis usually begin as avesicle, but may also beerythematous papules, urticarial-like wheals, excoriations, crusts, orrarely, large bullae. The lesionsmay be grouped, giving a
  114. 114. “herpetiform” appearance. Once thelesions have resolved, there may betransient hyper- orhypopigmentation. The lesions areusually intensely pruritic,accompanied by burning andstinging. Many patients experience
  115. 115. localized burning, stinging, andpruritus approximately eight to 12hours before the onset of lesions,and many are able to predict aneruption. Rarely, the lesions may beasymptomatic. There is symmetricdistribution along the extensor
  116. 116. surfaces, including the elbows,knees, buttocks, shoulders, andsacral areas. Less frequently, thelesions are found on the scalp, face,hairline, and the posterior neck.Involvement of the palms and soles
  117. 117. is rare, and mucous membranelesions are uncommon.Dermatitis herpetiformis ischaracterized histopathologically byneutrophilic microabscesses indermal papillae, dermal infiltrationof neutrophils and eosinophils, and
  118. 118. the formation of subepidermalvesicles. Blisters form within thelamina lucida. Dermal blood vesselsmay be surrounded by alymphohistiocytic infiltrate as well.Direct immunofluorescencereveals granular deposition of
  119. 119. IgA in the tips of dermal papillae.In areas corresponding to IgAdeposits, there may also becomplement deposition. IgA andIgG antireticulin and antien-domysial antibodies have beendetected in dermatitis herpetiformis
  120. 120. patients sera.9 An increasedincidence of antinuclear andantithyroid microsomal antibodiesare also found in these patients.TREATMENTPatients will experience promptrelief of lesions within one to two
  121. 121. days of initializing treatment withdapsone or sulfapyridine.10 It isimportant to remember to alwayscheck glucose-6-phosphatedehydrogenase (G6PD) andbaseline complete blood countlevels before starting dapsone,
  122. 122. followed by complete blood cellcounts every month to monitor forsigns of hemolytic anemia. A slightdecrease in hemoglobin is common.Other methods of treatment includedietary modification. One form isthe gluten-free diet, which has been
  123. 123. found to improve both intestinaland skin lesions. The onset is slow,taking from five months to one yearbefore the effect is noted; however,close adherence to the diet willallow patients to significantlydecrease or stop using the
  124. 124. medications. Another diet that hasbeen found to alleviate skin lesionsis the elemental diet, consisting offree amino acids, short chainpolysaccharides and small amountsof triglycerides. Alleviation of skinlesions can occur within a few
  125. 125. weeks of starting the diet, even ifthe patient ingests large amounts ofgluten, but this diet is difficult totolerate.COURSE ANDCOMPLICATIONS
  126. 126. Dermatitis herpetiformis follows aprolonged course, lasting up toyears. Approximately one third ofpatients eventually havespontaneous remission.9 Dermatitisherpetiforms responds well tomedications and diet, and has a
  127. 127. good prognosis. Associatedmanifestations that may causecomplications include the gluten-sensitive enteropathy, which cancause steatorrhea, abnormald-xylose absorption, and anemia.There has also been an increased
  128. 128. incidence of atrophic gastritis andachlorhydria in patients with glutensensitivity. Reports of increasedfrequency of gastrointestinallymphomas have also been noted,from which the gluten-free diet hasbeen found to be protective.
  129. 129. Patients with dermatitisherpetiformis have also been foundto have an increased incidence ofother autoimmune disorders,including thyroid disease, type 1diabetes mellitus, systemic lupus
  130. 130. erythematosus, vitiligo, andSjögrens syndrome.Linear IgA DiseaseLinear IgA dermatosis is a rareautoimmune bullous disorder,characterized by linear depositionof IgA along the basement
  131. 131. membrane.11 It was originallythought to be a manifestation ofdermatitis herpetiformis; however,based on immunopathology andimmunogenetics, it is now knownthat linear IgA dermatosis is adistinct entity. Chronic bullous
  132. 132. disease of childhood shares thesame linear deposition of IgA alongthe basement membrane and isbelieved to be a variant of linearIgA dermatosis.Linear IgA dermatosis mostcommonly presents in patients older
  133. 133. than 30 years.11 Chronic bullousdisease of childhood occurs inyoung children, usually presentingin those younger than five years.12The lesions of linear IgAdermatosis consist of pruritic,annular papules, vesicles, and
  134. 134. bullae that are found in groups.There is a predilection for theextensor surfaces, with symmetricdistribution. Lesions are seen on theelbows, knees, and buttocks.Because of itching, excoriations
  135. 135. will lead to the formation of manycrusted papules.Chronic bullous disease ofchildhood presents with abruptonset of tense bullae on aninflamed, erythematous base and isaccompanied by pruritus and a
  136. 136. burning sensation. The lesions aremost frequently found on or nearthe genitalia, but may also be foundon other areas, including the face,especially the perioral region. Oralulcers are noted in 50 percent ofcases.12 Characteristic “collarettes”
  137. 137. of blisters often form as new lesionsarise in the periphery of old lesions.In both forms of linear IgAdermatosis, mucous membraneinvolvement may occur and rangesin severity from mild oral ulcers tosevere oral or conjunctival disease.
  138. 138. On histopathology, in linear IgAdermatosis and chronic bullousdisease of childhood, the bullae aresubepidermal, with collections ofneutrophils along the basementmembrane and occasionally in thedermal papillary tips. On direct
  139. 139. immunofluorescence, deposition ofIgA in a linear pattern is notedalong the basement membrane.There may also be deposition ofIgG and C3.TREATMENT
  140. 140. Skin lesions in linear IgAdermatosis and chronic bullousdisease of childhood respondrapidly when treated with dapsoneor sulfa-pyridine. Again, there is arisk of hemolytic anemia in G6PD-deficient patients. Some patients
  141. 141. may require low-dose prednisoneinitially to suppress blisterformation.COURSE ANDCOMPLICATIONSThe course of linear IgA dermatosisis variable and unpredictable. The
  142. 142. disease may spontaneously remit insome cases; however, it may last foryears with few episodes ofremission in others. Chronic bullousdisease of childhood follows amuch different course, with
  143. 143. resolution occurring within twoyears of onset in most cases.Subepidermal separation Tense bullaFlacid bullaIntraepidermal separation