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Skin hyperreactivity response (pathergy) in Behçet's disease: Usefulness of direct immunofluorescence
Volume 23 Number 2, Part I August 1990
Correspondence 329
removal of the dressing. Moisture retained under lowmoisture vapor transmission rate dressings may take up to 20 minutes to desorb from human or animal epidermis. This artifact causes artificially high TEWL values immediately after removal of the dressing. Measurements taken immediately after removal of the dressing can be used to assess skin maceration, but this does not reflect transpiration through the returning epithelial barrier. When one waits the necessary 20 minutes after dressing removal to measure TEWL, the well-documented effects of moisture-retentive dressingson the return of epithelial barrier function become clearer, as seen in Table I. Table l. TEWL measurements through epidermal wounds on swine dressed with drying versus moisture-retentive dressings TF.WL (mean gm/m 2/ hr ± SEI\-f)" Day after wounding
Gauze'!
Polyurethane film:\:
Ilydrocolloid§
4 7
93 ± 5 55 ± 7
101 :::: 7 33 611
78 ± 5~ 18 ± 4~
=
• As measured with EP-l Servo-mod cvaporimeter on 12 wounds per mean, 20 minutes after removal of dressing. t 16-ply gauze sponges (Johnson & Johnson Products.NewBrunswick, N.J.)
:t:TEGADERM (3M Co., Minneapolis, Minr..). §f)uoDERM (Conva'Tcc Division, ~. R. Squibb, Princeton, N.J.). IISig1ificanlly lower than gauze (fJ < D.OS) on same day. ~Signifieantly lower than gauze or polyurethane (fJ < 0.05) on same day.
These results are closely paralleled (± 10 gmjm 2jhr) by our unpublished findings on human skin. Laura Bolton. PhD, and Louis Pirone, BS Wound Healing Research Institute Conva'Tec, A Squibb Company Princeton. NJ 08543-5254
Bullous pemphigoid and multiple sclerosis To the Editor: We read with interest the report by Masouyeet al. ofthree patients with bullous pemphigoid and multiple sclerosis (J AM ACAD DERMATOL 1989;21:638). It was, however, a surprise to learn that there had only been one prior such report detailing three patients with both diseases. We have treated two such patients during the past month. Our first patient was a 78-year-old woman with severe multiple sclerosis for more than 20 years, and our more recent patient was a 62-year-old man with 30 years of multiple sclerosis. The diagnosis of bullous pemphigoid was confirmed by histologic examination and by direct and indirect immunofluorescence. The clinical response to oral prednisolone and azathioprine was no different from other bullous pemphigoid patients, although skin erosions and pressure areas, including one under a penile condomcatheter, wereslowto heal and delayed discharge by several days. Prevalencefigures for multiple sclerosis must be interpreted with caution. First, the disease can be extremely difficult to diagnose,with symptoms and signs fluctuating for many years as the disease evolves. Second, multiple sclerosis is not a notifiabledisease and voluntary registers are not confined to geographically and numerically defined populations. Third, the prolonged survival of affected patients with better medical care and an increase in the life expectancy of the general population results in higher prevalence rates, although the incidence of the disease may remain unchanged. With these limitations the prevalence rate for multiple sclerosis in the United Kingdom is approximately 60 per 100,000. 2 In our referral area the incidence of bullous pemphigoid is three cases per 100,000 annually. The probability, therefore, of these two diseases being associated by chance is statistically remote. We support Masouye et al. in their contention that this association may be the result of the coexistence of autoimmune phenomena.
Reply To the Editor: I thank Bolton and Pirone for their com-
ments regarding the methodology used in our studies of transepidermal water loss (TEWL) during wound healing. During our experiments we waited approximately 20 minutes after uncovering wounds before TEWL measurements were obtained and dressings were changed. The word immediately (page 756, paragraph 3) in our report is admittedly confusing. It refers to the initial measurements 20 minutes after blister wounds were unroofed. I am gratified to see that the results in their swine experiments are relatively close to those in the human experiments that we have published. Robert A. Silverman. MD Annandale, Virginia
Kurt Gebauer, MBBS, Jonathan Cox, MB, Behir, John Gartside. FRCP, and Tony Navaratnam. FRCP Derbyshire Royal Infirmary Derby. England REFERENCE I. Matthews WB, Acheson ED, Batchelor Jr, et al, Mc/vlpinc's multiple sclerosis. Edinburgh: Churchill Livingstone, 1984.
Skin hyperreactivity response (pathergy) in Behcet's disease: Usefulness of direct immunofluorescence To the Editor: We read with interest the report by Gilhar et al. regarding the skin hyperreactivity response (pathergy) in Behcct's disease (8D) (J AM ACAf) DERMA-:'OL
Journal of the
American Academy of
330 Correspondence 1989;21: 54~-5 2) . We agree with the conclusion that any nonspecific intracutaneous injection is a good tool for the diagnosis of BD and emphasize the usefulness of direct imrnunofiorescence. In 1981 we; reported the immune~ogic findings of a prospectivestudy of skin biopsyspecimens performed 48 hours after injection of sterile distilled water in 50 patients with BD. The diagnosis of BD was assessed according to the criteria of O'Duffy et al.2 or of Mason and Barnes.' Half of the BO cases included patients with active disease, and half were patients in remission, with or without treatment. The 50 patients with BD werecompared with40 controlsubjects having infectious uveitis, cataracts, and various inflammatory diseases, some caused by autoimmunity. In all ~ases, frozen.sections for immunofluorescence study were Incubated with fluorescein-conjugated rnonospecific antiserum to human IgG, IgM, [gA, and C3. Immunoglobulinand/or C3 vascular deposits werefound in 31 of 50 patients with BD (62%) and in 11 of 40 control subjects (27%). A routine microscopicexamination was simultaneously performed in 41 patients (30 with BD and 11 controlsubjects). Specificleukocytoclastic vasculitiswith or withoutfibrinoiddepositswasfound in 10000 patients with BD and in 2 of 11 control subjects. Our study demonstrated that we increased the sensitivity of the test by the use of immunofluorescence. Our results usually cor~elated with the disease activity. In our opinion, positive unmunofluorescence supported the conceptthat immune complexes are probably involved in the pathogenesis of BD.
Janine Wechsler, MD,a Bertrand Wechsler, MD,b Jean Revuz, MD,c and Pierre Godeau, MIY Departments of Pathology' and Dermatology," Henri-Mondor Hospital, Creteil, and Department of Internal Medicine,b Pirie Hospital, Paris, France REFERENCES
1. WechslerJ, WechslerB, Herrernan G,el al. Maladiede Bebeet. Etude en immunofluorescence del'intradermoreaction al'eau distillee. Valeurdiagnostique apropos de 50 malades, Med Interne 1981;16:112-7. 2. O'Dt:ffy lD, Carney lA, Dehodar S. Bchcet's disease. Report of ~ O ca.c; es, 3 with new manifestations. Am Intern Med 1971;75:561-7Q.
Derma tology
3. Mason RM, Barnes CG. Bchcet's syndrome with arthritis. Ann Rheum Dis 1969;28:95-103.
Reply To the Editor: We appreciate the interest in our article shown by Wechsler et al., which focused on the skin hyperreactivity response in Behcet's disease. As we mentioned, many investigators failed to demonstrate either signs ofvasculitis or deposition ofimmunereactants at the site of cutaneous hyperreactivity in Behcet's disease. Haim 1 investigated the histologic and immunofluorescence features at 12, 24, 48, and 72 hours after trauma and did not find any vascularchanges or depositionof immunoglobulins and/or complements. However, there are other studies that described vascular and perivascular changes. Jorizzo- believes that only lesions documented to show a neutrophilic vascular reaction or leukocytoclastic vasculitis should be included in the diagnostic criteria for Behcet's disease. Wechsler et al. revealed in an immunofluorescence study a deposition of immune reactants in the vessel wall in 62% of cases with Behcet's disease48 hoursafter injection of sterile distilled water. We find this observation to be of interest because Cochrane et al.' and Braverman and Yen4 found that in spontaneous lesions of more than 24 hours' duration, the immune reactants are undetectable by direct immunofluorescence. Amos Gilhar, MD Skin Research Laboratory Faculty of Medicine, Technion P.o.R. 9649, Haifa 31096, Israel REFEREI'CES
I. Haim S. The pathogenesis of lesions in Bencet's disease. Dermatologica 1979;158:31-7. 2. JorizzoJ. Behcet's disease. Arch DermatoI1986;122:556-8. 3. CochraneCC, Weigle WD, Dixon FJ. The roleofpolymorphonuclear leucocytes in the initiation and cessation of the Arthus vasculitis. J Exp Med 1959;110:481-94. 4. Braverman 1M, Yen A. Demonstration of immune complexes in spontaneous and histamine-induced lesions and in normalskin of patients with leukocyroclastic angiitis. J Invest Derrr.atol ~ 974;64:105-: 2.
Correspondence 329
removal of the dressing. Moisture retained under lowmoisture vapor transmission rate dressings may take up to 20 minutes to desorb from human or animal epidermis. This artifact causes artificially high TEWL values immediately after removal of the dressing. Measurements taken immediately after removal of the dressing can be used to assess skin maceration, but this does not reflect transpiration through the returning epithelial barrier. When one waits the necessary 20 minutes after dressing removal to measure TEWL, the well-documented effects of moisture-retentive dressingson the return of epithelial barrier function become clearer, as seen in Table I. Table l. TEWL measurements through epidermal wounds on swine dressed with drying versus moisture-retentive dressings TF.WL (mean gm/m 2/ hr ± SEI\-f)" Day after wounding
Gauze'!
Polyurethane film:\:
Ilydrocolloid§
4 7
93 ± 5 55 ± 7
101 :::: 7 33 611
78 ± 5~ 18 ± 4~
=
• As measured with EP-l Servo-mod cvaporimeter on 12 wounds per mean, 20 minutes after removal of dressing. t 16-ply gauze sponges (Johnson & Johnson Products.NewBrunswick, N.J.)
:t:TEGADERM (3M Co., Minneapolis, Minr..). §f)uoDERM (Conva'Tcc Division, ~. R. Squibb, Princeton, N.J.). IISig1ificanlly lower than gauze (fJ < D.OS) on same day. ~Signifieantly lower than gauze or polyurethane (fJ < 0.05) on same day.
These results are closely paralleled (± 10 gmjm 2jhr) by our unpublished findings on human skin. Laura Bolton. PhD, and Louis Pirone, BS Wound Healing Research Institute Conva'Tec, A Squibb Company Princeton. NJ 08543-5254
Bullous pemphigoid and multiple sclerosis To the Editor: We read with interest the report by Masouyeet al. ofthree patients with bullous pemphigoid and multiple sclerosis (J AM ACAD DERMATOL 1989;21:638). It was, however, a surprise to learn that there had only been one prior such report detailing three patients with both diseases. We have treated two such patients during the past month. Our first patient was a 78-year-old woman with severe multiple sclerosis for more than 20 years, and our more recent patient was a 62-year-old man with 30 years of multiple sclerosis. The diagnosis of bullous pemphigoid was confirmed by histologic examination and by direct and indirect immunofluorescence. The clinical response to oral prednisolone and azathioprine was no different from other bullous pemphigoid patients, although skin erosions and pressure areas, including one under a penile condomcatheter, wereslowto heal and delayed discharge by several days. Prevalencefigures for multiple sclerosis must be interpreted with caution. First, the disease can be extremely difficult to diagnose,with symptoms and signs fluctuating for many years as the disease evolves. Second, multiple sclerosis is not a notifiabledisease and voluntary registers are not confined to geographically and numerically defined populations. Third, the prolonged survival of affected patients with better medical care and an increase in the life expectancy of the general population results in higher prevalence rates, although the incidence of the disease may remain unchanged. With these limitations the prevalence rate for multiple sclerosis in the United Kingdom is approximately 60 per 100,000. 2 In our referral area the incidence of bullous pemphigoid is three cases per 100,000 annually. The probability, therefore, of these two diseases being associated by chance is statistically remote. We support Masouye et al. in their contention that this association may be the result of the coexistence of autoimmune phenomena.
Reply To the Editor: I thank Bolton and Pirone for their com-
ments regarding the methodology used in our studies of transepidermal water loss (TEWL) during wound healing. During our experiments we waited approximately 20 minutes after uncovering wounds before TEWL measurements were obtained and dressings were changed. The word immediately (page 756, paragraph 3) in our report is admittedly confusing. It refers to the initial measurements 20 minutes after blister wounds were unroofed. I am gratified to see that the results in their swine experiments are relatively close to those in the human experiments that we have published. Robert A. Silverman. MD Annandale, Virginia
Kurt Gebauer, MBBS, Jonathan Cox, MB, Behir, John Gartside. FRCP, and Tony Navaratnam. FRCP Derbyshire Royal Infirmary Derby. England REFERENCE I. Matthews WB, Acheson ED, Batchelor Jr, et al, Mc/vlpinc's multiple sclerosis. Edinburgh: Churchill Livingstone, 1984.
Skin hyperreactivity response (pathergy) in Behcet's disease: Usefulness of direct immunofluorescence To the Editor: We read with interest the report by Gilhar et al. regarding the skin hyperreactivity response (pathergy) in Behcct's disease (8D) (J AM ACAf) DERMA-:'OL
Journal of the
American Academy of
330 Correspondence 1989;21: 54~-5 2) . We agree with the conclusion that any nonspecific intracutaneous injection is a good tool for the diagnosis of BD and emphasize the usefulness of direct imrnunofiorescence. In 1981 we; reported the immune~ogic findings of a prospectivestudy of skin biopsyspecimens performed 48 hours after injection of sterile distilled water in 50 patients with BD. The diagnosis of BD was assessed according to the criteria of O'Duffy et al.2 or of Mason and Barnes.' Half of the BO cases included patients with active disease, and half were patients in remission, with or without treatment. The 50 patients with BD werecompared with40 controlsubjects having infectious uveitis, cataracts, and various inflammatory diseases, some caused by autoimmunity. In all ~ases, frozen.sections for immunofluorescence study were Incubated with fluorescein-conjugated rnonospecific antiserum to human IgG, IgM, [gA, and C3. Immunoglobulinand/or C3 vascular deposits werefound in 31 of 50 patients with BD (62%) and in 11 of 40 control subjects (27%). A routine microscopicexamination was simultaneously performed in 41 patients (30 with BD and 11 controlsubjects). Specificleukocytoclastic vasculitiswith or withoutfibrinoiddepositswasfound in 10000 patients with BD and in 2 of 11 control subjects. Our study demonstrated that we increased the sensitivity of the test by the use of immunofluorescence. Our results usually cor~elated with the disease activity. In our opinion, positive unmunofluorescence supported the conceptthat immune complexes are probably involved in the pathogenesis of BD.
Janine Wechsler, MD,a Bertrand Wechsler, MD,b Jean Revuz, MD,c and Pierre Godeau, MIY Departments of Pathology' and Dermatology," Henri-Mondor Hospital, Creteil, and Department of Internal Medicine,b Pirie Hospital, Paris, France REFERENCES
1. WechslerJ, WechslerB, Herrernan G,el al. Maladiede Bebeet. Etude en immunofluorescence del'intradermoreaction al'eau distillee. Valeurdiagnostique apropos de 50 malades, Med Interne 1981;16:112-7. 2. O'Dt:ffy lD, Carney lA, Dehodar S. Bchcet's disease. Report of ~ O ca.c; es, 3 with new manifestations. Am Intern Med 1971;75:561-7Q.
Derma tology
3. Mason RM, Barnes CG. Bchcet's syndrome with arthritis. Ann Rheum Dis 1969;28:95-103.
Reply To the Editor: We appreciate the interest in our article shown by Wechsler et al., which focused on the skin hyperreactivity response in Behcet's disease. As we mentioned, many investigators failed to demonstrate either signs ofvasculitis or deposition ofimmunereactants at the site of cutaneous hyperreactivity in Behcet's disease. Haim 1 investigated the histologic and immunofluorescence features at 12, 24, 48, and 72 hours after trauma and did not find any vascularchanges or depositionof immunoglobulins and/or complements. However, there are other studies that described vascular and perivascular changes. Jorizzo- believes that only lesions documented to show a neutrophilic vascular reaction or leukocytoclastic vasculitis should be included in the diagnostic criteria for Behcet's disease. Wechsler et al. revealed in an immunofluorescence study a deposition of immune reactants in the vessel wall in 62% of cases with Behcet's disease48 hoursafter injection of sterile distilled water. We find this observation to be of interest because Cochrane et al.' and Braverman and Yen4 found that in spontaneous lesions of more than 24 hours' duration, the immune reactants are undetectable by direct immunofluorescence. Amos Gilhar, MD Skin Research Laboratory Faculty of Medicine, Technion P.o.R. 9649, Haifa 31096, Israel REFEREI'CES
I. Haim S. The pathogenesis of lesions in Bencet's disease. Dermatologica 1979;158:31-7. 2. JorizzoJ. Behcet's disease. Arch DermatoI1986;122:556-8. 3. CochraneCC, Weigle WD, Dixon FJ. The roleofpolymorphonuclear leucocytes in the initiation and cessation of the Arthus vasculitis. J Exp Med 1959;110:481-94. 4. Braverman 1M, Yen A. Demonstration of immune complexes in spontaneous and histamine-induced lesions and in normalskin of patients with leukocyroclastic angiitis. J Invest Derrr.atol ~ 974;64:105-: 2.