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Pemphigus in remission: Value of negative direct immunofluorescence in management
Pemphigus in remission: Value of negative direct immunofluorescence in management K. V. Ratnam, MRCP (UK), and Bryan K. Pang, MBBS Singapore Background: Pemphigus vulgaris is characterized by relapses and remission, and there are currently no sensitive markers to predict remission. Objective: Our purpose was to determine if direct immunofluorescence (DIF) performed during clinical remission of pemphigus is useful in management of the disease. Methods: Twenty-eight patients with pemphigus that was in clinical remission (i.e., patients who were taking low-dose prednisolone [10 mgyday] and had been blister-free for at least 6 months) underwent DIF. Therapy was then discontinued and patients were prospectively followed up for 5 years. Results:Twenty-two patients had negative results and six patients had positive results ofDIF. The disease remained in remission in three quarters of the patients with negative results of DIF. Of those who had a relapse, intercellular C3 on DIF and oral lesions on initial presentation were important risk factors, and the relapses in patients with negative results of DIF were mild. The biopsy site was unimportant. All patients with positive results of DIF had major relapses within 3 months of cessation of therapy. Conclusion: DIF should be performed before therapy is discontinued. A negative DIF finding is a good indicator of remission in pemphigus. (J AM ACAD DERMATOL 1994;30:547-50.)
Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of serum autoantibodies, acantholysis, and the formation of intraepithelial vesicles in the skin and mucous membranes.' Its course is variable and unpredictable.i with relapses occurring between 2 months to lO years. Many studies have reported some correlation between disease activity and serum antibody titers. 3-6 However, only 80% of patients with PV have circulating IgO autoantibodies," and serial antibody titers have not been consistent enough to be used as a guide for therapy and prognosis.v 9 Direct immunofluorescence (DIF) is more sensitive than indirect immunofluorescence (I1F) in diagnosing PV.lo David et al.'! showed that DIF may have value if it is performed during clinical remission. However, there are no long-term studies to show whether DIF is helpful in the management of PV when it is performed during remission. Our goal was to determine whether DIF has any From the National Skin Centre. Accepted for pubJication Sept. 7. 1993. Reprint requests: K. V. Ratnam, MRCP, National Skin Centre, I Mandalay Rd., Singapore 1130. Copyright © 1994 by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0
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value in predicting relapse when it is performed during clinical remission of PV and whether the site of biopsy is important. We also investigated the risk factors for relapse during clinical remission of PV and pemphigus foliaceus (PF).
MATERIAL AND METHODS Twenty-eight patients with pemphigus (19 with PV and nine with PF) who were in clinical remission were recruited prospectively for the study from 1983 to 1988. Clinical remission was defined as a state in which no new blisters developed while the patient was taking low-dose prednisolone (between 10 to 20 mg/day). After a 6-month to l-year period of clinical remission, DIF was performed either on normal forearm skin or close to a previous biopsy site. Patients with negative results of DIF had their medications discontinued. Treatment was also discontinued in six patients who had positive results of DIF and whose disease was in clinical remission. The clinical severity of the disease in all patients who had a relapse was compared with the severityof their disease at initial presentation and graded according to the extent of involvement: severe (>50%), moderate (20% to 50%), mild «20%), and minimal «5%). IIF was performed 3 months after the initial diagnosis. The immunofluorescence procedures used were described by Beutner et aL/2 Monkey esophagus was used as a substrate for IIF.
547
Journal of the American Academy of Dermatology April 1994
548 Ratnam and Pang Table I. Immunofluorescence and clinical profile of patients with pemphigus on initial presentation PV
Total No. Positive DIF PositiveIIF DIF: C3 deposits Oral mucosal involvement
19 19/19(100%) 10/19 (52.6%) 6/19 (42.1%) 9/19 (47.4%)
PF
9 9/9 (100%) 4/9 (44.4%) 3/9 (33.3%) 0/9 (0%)
RESULTS Medication was discontinued for 22 patients with negative DIF findings and six patients with positive DIF findings whose disease was in clinical remission. Ten men (28 to 59 years of age) and nine women (17 to 59 years of age) had PV. All nine patients with PF were women (18 to 75 years of age). The patients with PV and PF had been under treatment for 0.8 to 10 years (mean, 4.6 years) and 1.2 to 12.8 years (mean, 6.5 years), respectively. The follow-up period after discontinuatiort of treatment was 1.5 to 9.5 years (mean, 5 years). On initial presentation (Table I), all patients with PV and PF who had DIF performed had positive results, whereas only 10 of 19 patients with PV (52.6%) and 4 of 9 patients with PF (44.4%) had positive results of IIF. DIF C3 deposits were found in 6 of 19 patients with PV (42.1 %) and three of nine patients with PF (33.3%). Nine of 19 patients with PV (47.4%) but none of the patients with PF had oral mucosal involvement on initial presentation. After discontinuation of treatment (Table II), the disease of most patients with negative DIF findings (73.3% of patients with PV and 85.7% of patients with PF) remained in remission. Only five patients with negative results of DIF (22.7%) had a relapse. Of those five patients, two (13.3%) had a relapse within the first 6 months, one (6.7%) had a relapse at 2.5 years, and one (6.7%) had a relapse 4.5 years after cessation of treatment. Only one of seven patients with PF with negative results of DIF (14.3%) had a relapse, and this was within the first 6 months after discontinuation of treatment. All six patients with PF and PV who had positive DIF findings had a relapse within 3 months after cessation of treatment. Four ofthese patients had positive results of IIF on initial presentation. All patients had negative results of lIF at the time treatment was discontinued. The severity of disease during the relapse of all
Table II. Follow-up of patients with pemphigus who had negative results of DIF after cessation of therapy PV
PF
Total No. of patients with 15 7 negative results of DIF Patients with negative results 11 (73.3%) 6 (85.7%) of DIF who did not have a relapse Patients with negative results of DIF who had a relapse: 2 (13.3%) 1 (14.3%) <6mo 1 (6.7%) 21/ 2 yr 0 4% yr 1 (6.7%) 0
patients with negative DIF findings was mild compared with the severity of disease at their initial clinical presentation (Table III). Only two of five patients who had a relapse had cutaneous involvement, which was of minimal severity. The remaining four patients who had a relapse had oral ulcers only. The relapses were easily controlled with a short course of low-dose oral prednisolone (10 mg daily) and topical steroids. However, all patients with PF and PV who had positive results of DIF had a relapse of the disease within 3 months that was of moderate severity and required prednisolone, 30 to 60 mg/day, for control. Two of the five who had a relapse had positive IIF findings at initial presentation. For patients with negative DIF findings who had a relapse, risk factors were identifiable in the patients with PV but not in the patients with PF. If both oral mucosal involvement and DIF C3 deposits were present on initial presentation, the chance of relapse with negative results of DIF was 100% (three of three patients with PV). DISCUSSION
Remission of pemphigus can be induced with immunosuppressive agents in most instances. The most difficult management decision is how to maintain remission with the least medication. Many previous studies that used clinical criteria as the sole management guideline achieved remission in only 11% to 57% of patients with pemphigus. 13-16 The poor outcome may be related to a lack of objective criteria to monitor disease activity. In this study we showed that DIF performed during clinical remission of pemphigus is valuable in management of the disease.
Journal of the American Academy of Dermatology Volume 30, Number 4
Ratnam and Pang 549
Table III. Clinical features of patients with pemphigus with negative results of DIF who had a relapse Severityof pemphigus
PadentNo.
1
2 3 4 5
Disease
At initial presentation
PV PV PV PV PF
Mild Mild Moderate Mild Moderate
In our series the disease of a majority of the patients with negative DIF findings (73 .3% of patients with PV and 85.7% of patients with PF) remained in clinical remission after discontinuation of treatment. Only 22.7% of the patients with negative results of DIF had a relapse during a mean follow-up period of 5 years. Because the binding of pemphigus antibodies to intercellular substance has been implicated as the pathogenetic mechanism of acantholysis, 17-20 negative results of DIF may imply immunologic remission of the disease, thus accounting for the low incidence of relapse . This hypothesis is possibly further supported by the finding that our six patients with positive DIF findings had a relapse of moderate severity within 3 months after discontinuation of treatment, which indicates that positive DIF findings obtained while the disease is in remission may indicate a high relapse potential. Because our study included only a small number of patients with positive results of D IF, further studies will be necessary. Similar findings with respect to relapse in patients with positive results of DIF have been reported. II The short-term prognosis of patients with PV and PF who have negative DIF findings is the same, that is, 13.3% and 14.3% of patients, respectively, had a relapse within the first 6 months after discontinuation of treatment. However, long-term follow-up showed that another 13.4% of patients with PV but not of patients with P F had a relapse (one had a relapse at 2.5 years and one had a relapse at 4.5 years). This contrasts with the results of a study by David et al., II who suggested that negative results of DIF is a possible marker for an apparent cure of the disease. However , only eight patients with pemphigus who had negative results of DIF with a maximum 20-month follow-up period were recruited in their study. Therefore long-term follow-up is required even for patients with pemphigus who have negative
At relapseon cessationof treiltmenl
Minimal
Minimal
Remarks
Mouth ulcers Few scalp erosions Mouth ulcers Mouth ulcers Few facial erosions
results ofDIF; we recommend a minimum follow-up period of 5 years after stopping treatment. The cause of relapse in patients with negative results of DIF is unknown. An unlikely possibility is that it is caused by sampling errors or technical problems. These problems can be minimized by repeating DIF, but this was not undertaken in our study because of our patients' reluctance to undergo DIF a second time in the absence of clinical disease. Because the severity of disease after these in patients with negative results of DIF was much less severe compared with their disease at initial presentation and could be easily controlled by low-dose steroids, there may be other mechanisms that account for the minor relapses in these patients. Many studies have reported adverse prognostic factors in pemphigus, which include older age at disease onset,21 extensive cutaneous involvement,14 rapid progression before treatment,22 institution of treatment after 6 months of disease.I' high-dose prednisolone (> 180 mg daily) required to control disease activity,22 and py24 rather than other pemphigus subtypes. In our series both oral mucosal involvement and DIF C3 deposits on initial presentation were risk factors for relapse in patients with PY with negative results of DIP. Seidenbaum et at 23 also reported that patients with oral mucosal involvement on initial presentation have an increased chance of relapse. In their series, these patients responded to therapy more slowly than patients with skin lesions only and they required higher doses of steroids for longer periods. However, we did not observe any such association in our study (data not shown). We did not find DIF helpful in predicting pemphigus relapse. None of the patients with pemphigus had positive results of UF at the time of relapse. In addition, we found that biopsy specimens can be ob-
550 Ratnam and Pang tained from any site for DIF, as previously report-
00. 25, 26 DIF performed during clinical remission ofpemphigus is valuable in management of the disease. Negative results of DIF may be viewed as a state of immunologic remission in pemphigus, because most patients with negative results of DIF did not have a relapse after treatment was discontinued. However, there were not enough patients in the study to indicate clearly whether the converse is true. Therefore treatment can be stopped in patients with negative results of D IF, including patients with PV with risk factors, who have a significantly increased chance of relapse. Because patients with positive results ofDIF have a high chance of relapse, their treatment should not be discontinued. However, more data will be required to confirm this finding.
REFERENCES I. Beuther EH, Jordan RE. Demonstration of skin antibodies in sera of pemphigus vulgaris patients by direct immunofluorescent staining. Proc Soc Exp Bioi Med 1964; 117:505-
10. 2. Lever WF, Schaumburg-Lever G . Immunosuppressants and prednisolone in pemphigus vulgaris: therapeutic results obtained in 63 patients between 1961 and 1975. Arch Dermatol 1977;113 :1236-41. 3. Chorzelski TP, Von Weiss JF, Lever WF. Clinical significa nce of autoantibodies in pemphigus. Arch Dermatol 1966;93:570-6. 4. Sams WM Jr ., Jordan RE. Correlation of pemphigoid and pemphigus antibody titres with activity of disease. Br J DermatoI1971;84:7-13. 5. Weissman V, Feuerman EJ, Joshua H, et al. The correlation between the ant ibody titer in sera of patients with pemphigus vulgaris and their clinical state. J Invest DermatoI197H;71:107-9. 6. O'Loughlin S, Goldman GG, Provost IT. Fate of pemphigus antibody following successful therapy. Arch Dermatol 1978;114:1769-72. 7. Moy R, lordon RE. Immunopathology in pemphigus. Dermatol Clin 1983;1:72 -82. 8. Fitzpatrick RE, Newcomer YD. The correlation of disease activity and antibody titres in pemphigus. Arch Dermatol 1980;116:285-90. 9. Creswell SN, Black MM, Bhogal B, et a1. Correlation of
Journal of the American Academy of Dermatology April 1994
circulating intercellular antibody titres in pemphigus with disease activity. Clin Exp Dermatol 1981;6:477-83. 10. Judd KP, Lever WF. Correlation of antibodies in skin and serum with disease severity in pemphigus. Arch Dermatol 1979;115:428-32. 11. David M, Weissman-Katzenelson V, Ben-chetrit A, et a1. The usefulness of immunofluorescent tests in pemph igus pat ients in clinical remission. Br J Dermatol 1989; 120:391-5. 12. Beutner EH. Hale WH, Nisengard RF, et al. Defined immunofluorescence in clinical immunopathology. In: Beutner EH, Chorzelski TP, Bean SF, et al., eds. Immunopathology of the skin. 1st ed. Pennsylvania: Dowden H utch inson and Ross, 1973:197-247. 13. Lever WF, Schaumberg-Lever G. Treatment of pemphigus vulgaris: results obtained in 84 patients between 1961-1982. Arch Dermatol 1984;120:44-7. 14. Ryan JG. Pemphigus: a 20 year survey of experience with 70 cases. Arch Dermatol 1971;104:14-20. 15. Costello MJ, Jairno vich L, Dannenberg M. Treatment of pemphigus with corticosteroids. JAMA 1957;65:1249-52. 16. Hietanen J, Salo OP. Pemphigus: an epidemiological study of patients treated in Finnish hospitals between 1969 and 1978. Acta Derm VenereoI1982;62:491-6. 17. Michel B, Ko CS. Effects of pemph igus or bullous pemphigoid sera and leucocytes on normal human skin in organ culture: an in-vitro model for the study of bullous diseases. J Invest Dermatol 1974;62:541-2. 18. Michel B, Ko CS. An organ culture model for the study of pemphigus acantholysis . Br J Dermatol 1977;96:295-302. 19. Hashimoto K, Shafran KM , Webber PS, et al. Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. J Exp Med 1983;157:259-72 . 20. Ka wana S, Geoghegan WD, Jordan RE. Complement fixation by pemph igus antibody. III. Altered epidermal cell membrane intergrity mediated by pemph igus antibody a nd complement. J Invest Dermatol 1986;86:29-33. 21. Sav in JD. Some factors affecting prognosis in pemphigus vulgaris and pemphigoid. Br J DermatoI1981;104:415-20. 22. Ahmed AR, May R. Death in pemphigus. J AM ACAD DERMATOL 1982;7:221-8. 23. Seidenbaurn M. David M, Sandbank M . The course a nd prognosis of pemph igus: a review of l l S pat ients. Int J Dermatol 1988;27:580-4. 24. Ahmed AR. Pemphigus vulgaris: clinical features . Dermatol Clin 1983 ;1:171-7. 25. Bhogal B, Wojnarowska F, Black MM, et al. The distribution of immunoglobulins and C3 component of comp lement in multiple biopsies from the uninvolved and perilesional skin in pemphigus. Clin Exp DermatoI1986;11:49-53. 26. Grando SA, Terman AK, Stupina AS, et al. Ultrastructural study of clinically uninvolved skin of patients with pemphigus vulgaris. Clin Exp DermntoI1991;16:359·63.
Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of serum autoantibodies, acantholysis, and the formation of intraepithelial vesicles in the skin and mucous membranes.' Its course is variable and unpredictable.i with relapses occurring between 2 months to lO years. Many studies have reported some correlation between disease activity and serum antibody titers. 3-6 However, only 80% of patients with PV have circulating IgO autoantibodies," and serial antibody titers have not been consistent enough to be used as a guide for therapy and prognosis.v 9 Direct immunofluorescence (DIF) is more sensitive than indirect immunofluorescence (I1F) in diagnosing PV.lo David et al.'! showed that DIF may have value if it is performed during clinical remission. However, there are no long-term studies to show whether DIF is helpful in the management of PV when it is performed during remission. Our goal was to determine whether DIF has any From the National Skin Centre. Accepted for pubJication Sept. 7. 1993. Reprint requests: K. V. Ratnam, MRCP, National Skin Centre, I Mandalay Rd., Singapore 1130. Copyright © 1994 by the American Academy of Dermatology, Inc. 0190-9622/94 $3.00 + 0
16/1/51329
value in predicting relapse when it is performed during clinical remission of PV and whether the site of biopsy is important. We also investigated the risk factors for relapse during clinical remission of PV and pemphigus foliaceus (PF).
MATERIAL AND METHODS Twenty-eight patients with pemphigus (19 with PV and nine with PF) who were in clinical remission were recruited prospectively for the study from 1983 to 1988. Clinical remission was defined as a state in which no new blisters developed while the patient was taking low-dose prednisolone (between 10 to 20 mg/day). After a 6-month to l-year period of clinical remission, DIF was performed either on normal forearm skin or close to a previous biopsy site. Patients with negative results of DIF had their medications discontinued. Treatment was also discontinued in six patients who had positive results of DIF and whose disease was in clinical remission. The clinical severity of the disease in all patients who had a relapse was compared with the severityof their disease at initial presentation and graded according to the extent of involvement: severe (>50%), moderate (20% to 50%), mild «20%), and minimal «5%). IIF was performed 3 months after the initial diagnosis. The immunofluorescence procedures used were described by Beutner et aL/2 Monkey esophagus was used as a substrate for IIF.
547
Journal of the American Academy of Dermatology April 1994
548 Ratnam and Pang Table I. Immunofluorescence and clinical profile of patients with pemphigus on initial presentation PV
Total No. Positive DIF PositiveIIF DIF: C3 deposits Oral mucosal involvement
19 19/19(100%) 10/19 (52.6%) 6/19 (42.1%) 9/19 (47.4%)
PF
9 9/9 (100%) 4/9 (44.4%) 3/9 (33.3%) 0/9 (0%)
RESULTS Medication was discontinued for 22 patients with negative DIF findings and six patients with positive DIF findings whose disease was in clinical remission. Ten men (28 to 59 years of age) and nine women (17 to 59 years of age) had PV. All nine patients with PF were women (18 to 75 years of age). The patients with PV and PF had been under treatment for 0.8 to 10 years (mean, 4.6 years) and 1.2 to 12.8 years (mean, 6.5 years), respectively. The follow-up period after discontinuatiort of treatment was 1.5 to 9.5 years (mean, 5 years). On initial presentation (Table I), all patients with PV and PF who had DIF performed had positive results, whereas only 10 of 19 patients with PV (52.6%) and 4 of 9 patients with PF (44.4%) had positive results of IIF. DIF C3 deposits were found in 6 of 19 patients with PV (42.1 %) and three of nine patients with PF (33.3%). Nine of 19 patients with PV (47.4%) but none of the patients with PF had oral mucosal involvement on initial presentation. After discontinuation of treatment (Table II), the disease of most patients with negative DIF findings (73.3% of patients with PV and 85.7% of patients with PF) remained in remission. Only five patients with negative results of DIF (22.7%) had a relapse. Of those five patients, two (13.3%) had a relapse within the first 6 months, one (6.7%) had a relapse at 2.5 years, and one (6.7%) had a relapse 4.5 years after cessation of treatment. Only one of seven patients with PF with negative results of DIF (14.3%) had a relapse, and this was within the first 6 months after discontinuation of treatment. All six patients with PF and PV who had positive DIF findings had a relapse within 3 months after cessation of treatment. Four ofthese patients had positive results of IIF on initial presentation. All patients had negative results of lIF at the time treatment was discontinued. The severity of disease during the relapse of all
Table II. Follow-up of patients with pemphigus who had negative results of DIF after cessation of therapy PV
PF
Total No. of patients with 15 7 negative results of DIF Patients with negative results 11 (73.3%) 6 (85.7%) of DIF who did not have a relapse Patients with negative results of DIF who had a relapse: 2 (13.3%) 1 (14.3%) <6mo 1 (6.7%) 21/ 2 yr 0 4% yr 1 (6.7%) 0
patients with negative DIF findings was mild compared with the severity of disease at their initial clinical presentation (Table III). Only two of five patients who had a relapse had cutaneous involvement, which was of minimal severity. The remaining four patients who had a relapse had oral ulcers only. The relapses were easily controlled with a short course of low-dose oral prednisolone (10 mg daily) and topical steroids. However, all patients with PF and PV who had positive results of DIF had a relapse of the disease within 3 months that was of moderate severity and required prednisolone, 30 to 60 mg/day, for control. Two of the five who had a relapse had positive IIF findings at initial presentation. For patients with negative DIF findings who had a relapse, risk factors were identifiable in the patients with PV but not in the patients with PF. If both oral mucosal involvement and DIF C3 deposits were present on initial presentation, the chance of relapse with negative results of DIF was 100% (three of three patients with PV). DISCUSSION
Remission of pemphigus can be induced with immunosuppressive agents in most instances. The most difficult management decision is how to maintain remission with the least medication. Many previous studies that used clinical criteria as the sole management guideline achieved remission in only 11% to 57% of patients with pemphigus. 13-16 The poor outcome may be related to a lack of objective criteria to monitor disease activity. In this study we showed that DIF performed during clinical remission of pemphigus is valuable in management of the disease.
Journal of the American Academy of Dermatology Volume 30, Number 4
Ratnam and Pang 549
Table III. Clinical features of patients with pemphigus with negative results of DIF who had a relapse Severityof pemphigus
PadentNo.
1
2 3 4 5
Disease
At initial presentation
PV PV PV PV PF
Mild Mild Moderate Mild Moderate
In our series the disease of a majority of the patients with negative DIF findings (73 .3% of patients with PV and 85.7% of patients with PF) remained in clinical remission after discontinuation of treatment. Only 22.7% of the patients with negative results of DIF had a relapse during a mean follow-up period of 5 years. Because the binding of pemphigus antibodies to intercellular substance has been implicated as the pathogenetic mechanism of acantholysis, 17-20 negative results of DIF may imply immunologic remission of the disease, thus accounting for the low incidence of relapse . This hypothesis is possibly further supported by the finding that our six patients with positive DIF findings had a relapse of moderate severity within 3 months after discontinuation of treatment, which indicates that positive DIF findings obtained while the disease is in remission may indicate a high relapse potential. Because our study included only a small number of patients with positive results of D IF, further studies will be necessary. Similar findings with respect to relapse in patients with positive results of DIF have been reported. II The short-term prognosis of patients with PV and PF who have negative DIF findings is the same, that is, 13.3% and 14.3% of patients, respectively, had a relapse within the first 6 months after discontinuation of treatment. However, long-term follow-up showed that another 13.4% of patients with PV but not of patients with P F had a relapse (one had a relapse at 2.5 years and one had a relapse at 4.5 years). This contrasts with the results of a study by David et al., II who suggested that negative results of DIF is a possible marker for an apparent cure of the disease. However , only eight patients with pemphigus who had negative results of DIF with a maximum 20-month follow-up period were recruited in their study. Therefore long-term follow-up is required even for patients with pemphigus who have negative
At relapseon cessationof treiltmenl
Minimal
Minimal
Remarks
Mouth ulcers Few scalp erosions Mouth ulcers Mouth ulcers Few facial erosions
results ofDIF; we recommend a minimum follow-up period of 5 years after stopping treatment. The cause of relapse in patients with negative results of DIF is unknown. An unlikely possibility is that it is caused by sampling errors or technical problems. These problems can be minimized by repeating DIF, but this was not undertaken in our study because of our patients' reluctance to undergo DIF a second time in the absence of clinical disease. Because the severity of disease after these in patients with negative results of DIF was much less severe compared with their disease at initial presentation and could be easily controlled by low-dose steroids, there may be other mechanisms that account for the minor relapses in these patients. Many studies have reported adverse prognostic factors in pemphigus, which include older age at disease onset,21 extensive cutaneous involvement,14 rapid progression before treatment,22 institution of treatment after 6 months of disease.I' high-dose prednisolone (> 180 mg daily) required to control disease activity,22 and py24 rather than other pemphigus subtypes. In our series both oral mucosal involvement and DIF C3 deposits on initial presentation were risk factors for relapse in patients with PY with negative results of DIP. Seidenbaum et at 23 also reported that patients with oral mucosal involvement on initial presentation have an increased chance of relapse. In their series, these patients responded to therapy more slowly than patients with skin lesions only and they required higher doses of steroids for longer periods. However, we did not observe any such association in our study (data not shown). We did not find DIF helpful in predicting pemphigus relapse. None of the patients with pemphigus had positive results of UF at the time of relapse. In addition, we found that biopsy specimens can be ob-
550 Ratnam and Pang tained from any site for DIF, as previously report-
00. 25, 26 DIF performed during clinical remission ofpemphigus is valuable in management of the disease. Negative results of DIF may be viewed as a state of immunologic remission in pemphigus, because most patients with negative results of DIF did not have a relapse after treatment was discontinued. However, there were not enough patients in the study to indicate clearly whether the converse is true. Therefore treatment can be stopped in patients with negative results of D IF, including patients with PV with risk factors, who have a significantly increased chance of relapse. Because patients with positive results ofDIF have a high chance of relapse, their treatment should not be discontinued. However, more data will be required to confirm this finding.
REFERENCES I. Beuther EH, Jordan RE. Demonstration of skin antibodies in sera of pemphigus vulgaris patients by direct immunofluorescent staining. Proc Soc Exp Bioi Med 1964; 117:505-
10. 2. Lever WF, Schaumburg-Lever G . Immunosuppressants and prednisolone in pemphigus vulgaris: therapeutic results obtained in 63 patients between 1961 and 1975. Arch Dermatol 1977;113 :1236-41. 3. Chorzelski TP, Von Weiss JF, Lever WF. Clinical significa nce of autoantibodies in pemphigus. Arch Dermatol 1966;93:570-6. 4. Sams WM Jr ., Jordan RE. Correlation of pemphigoid and pemphigus antibody titres with activity of disease. Br J DermatoI1971;84:7-13. 5. Weissman V, Feuerman EJ, Joshua H, et al. The correlation between the ant ibody titer in sera of patients with pemphigus vulgaris and their clinical state. J Invest DermatoI197H;71:107-9. 6. O'Loughlin S, Goldman GG, Provost IT. Fate of pemphigus antibody following successful therapy. Arch Dermatol 1978;114:1769-72. 7. Moy R, lordon RE. Immunopathology in pemphigus. Dermatol Clin 1983;1:72 -82. 8. Fitzpatrick RE, Newcomer YD. The correlation of disease activity and antibody titres in pemphigus. Arch Dermatol 1980;116:285-90. 9. Creswell SN, Black MM, Bhogal B, et a1. Correlation of
Journal of the American Academy of Dermatology April 1994
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