vesiculobullous systemic lupus erythematosus

Yeung et al

Journal of the American Academy of

Dermatology

percutaneous absorption: Influence of hydration on A1- kanol permeation through hairless mouse skin. J Invest Dermatol 75:346-352, 1980.

4. Wester RC, Maibach HI: Relationship of topical dose and pemutaneous absorption in rhesus monkey and man. J Invest Dermatol 67:518-520, 1976.

5. Maibach HI, Stoughton RB: Topical corticosteroids. Med Clin North Am 57:1253-I265, 1973.

6. Reinfenrath WG, Robinson PB, Bolton VD, Aliff RE: Percutaneous penetration of mosquito repellants in the

hairless dog: Effect of dose on percent penetration. Fd Cosmet Toxicol 19:195-199, 1981.

7. Wedig HJ, Feldmann R J, Maibach HI: Percutaneous penetration of the magnesium sulfate adduct of di- pyrithione in man. Toxicol Appl Pharmaco141:1-6, 1977.

8. Roberts MS, Horlock E: Effect of repeated skin applica- tion on percutaneous absorption of salicylic acid. J Pharm Sei 67:1685-1687, 1978.

9. Gibaldi M, Kanig JL: Absorption of drugs through the oral mucosa. J Oral Ther Pharmacol 1:440-450, 1965.

Vesiculobullous systemic lupus erythematosus Report of two cases and a review of the literature

Charles Camisa , M.D . , and Haft M. Sharma, M.D.

Columbus, OH

Vesicles and bullae complicating systemic lupus erythematosus (SLE) are relatively uncommon. Two young women with SLE presented with vesiculobullous eruptions on sun-exposed areas that resembled dermatitis herpetiformis (DH) histologically. There were active visceral manifestations of SLE in both patients, including mesangioproliferative glomerulonephritis. Granular deposits of IgG and/or IgM, along with IgA, were demonstrated along the basement membrane of skin by direct immunofluorescence microscopy. Review of fifteen additional cases of vesiculobullous SLE reported in the literature suggests that this cutaneous manifestation of SLE is associated with a high incidence of IgA deposits in skin and glomerulonephritis. The following criteria for the diagnosis of a distinct subset of vesiculobullous skin lesions occurring in patients with SLE are proposed: (1) a diagnosis of SLE based upon American Rheumatism Association (ARA) criteria; (2) vesicIes and bullae arising upon but not limited to sun-exposed skin; (3) histopathology compatible with DH; (4) negative indirect immunofluorescence for circulating basement membrane zone (BMZ) antibodies; (5) direct immunofluorescence reveals IgG and/or IgM and often IgA at the BMZ. (J AM ACAD DERMATOL 9:924-933, 1983.)

From the Dep,'u-tment of Medicine, Division of Dermatology, and the Department of Pathology, Ohio State University Medical College.

A grant to cover the cost of color illustrations was provided by Owen Laboratories, Division of Dermatological Products of Texas, Inc., an affiliate of Alton Laboratories, Fort Worth, TX.

Accepted for publication March 18, 1983. Reprint requests to: Dr. Charles Camisa, Department of Medicine,

The Ohio State University, 4731 University Hospital Clinic, 456 Clinic Dr., Columbus, OH 43210.

924

While cutaneous manifestat ions of sys temic lupus erythematosus (SLE) occur frequently, the

complicat ion of a ves icular or bullous eruption is relatively uncommon. In three large series o f patients with SLE, skin lesions developed in 7 6 %

during the course of their illness. O f these, the incidence of blisters was 0 .04%, 4 .5%, and 8 .0%,

respectively, l-a The simultaneous occurrence of a

Volume 9 Number 6 December, 1983

Vesiculobullous systemic lupus elythematosus 925

Abbreviations used

ANA BMZ BP BUN CBC DH DIF ESR HPF IEM LBT LE PMN RBC SBE SLE WBC

anfinuclear antibody basement membrane zone bullous pemphigoid blood urea nitrogen complete blood (cell) count dermatitis herpetiformis direct immunofluorescence erythrocyte sedimentation rate high-power field immunoelectron microscopy lupus band test lupus erythematosus polymorphonuclear leukocytes red blood cell subacute bacterial endocarditis systemic lupus erythematosus white blood ceil

primary bullous disease in a patient with SLE must be differentiated from vesiculobullous SLE. For example, bullous pemphigoid (Bp),4-7 dermatitis herpetiformis (DH),8-1o porphyria cutanea tarda, 1, epidermolysis bullosa acquisita, 12 arid toxic epidermal necrolysis 1:~ have all been reported in association with SLE.

The task of differential diagnosis between vesiculobullous SLE and other bullous diseases is made more difficult by discrepancies in the literature. Clinical descriptions of blistering eruptions in SLE have ranged from large hemorrhagic bullae 14 to herpetiform vesicles? '~ Histopathologi- cally, biopsies of such lesions have been reported as nonacantholytic intraepidermal bullae with no inflammatory infiltrate,1 intraepidermal bullae containing polymorphonuclear leukocytes (PMN), and lymphocytes, 14-16 subepidermal blisters with degeneration of basal cells and dermal edema, 17 leukocytoclastic vasculitis, 18 and subepidermal blisters containing PMN, eosinophils, and lymphocytes with microabscesses at the tips of the dermal papillae. 1~,19,2~ We believe that this last group of patients with lesions that are his- topathologically similar to those of DH represents a distinct subset of blistering eruptions that can occur in association with SLE.

W e have had the opportunity to observe two young women with SLE who developed vesiculo-

bullous lesions in sun-exposed areas. Biopsies in both cases revealed the histologic alterations usually associated with DH. Direct immunofluorescence (DIF) microscopy of light-protected normal- appearing skin demonstrated granular deposits of IgG, IgM, and IgA at the basement membrane zone (BMZ). Both patients developed clinical evidence of renal disease that was documented by biopsy as mesangioproliferative glomerulonephritis. The kidney specimens gave positive results by DIF, and, with one exception, when a class of immunoglobulin was present in the skin, it was also found in the glomeruli.

CASE REPORTS Case 1

A 21-year-old white woman was well until August, 1978, when she developed choreiform movements of her right hand and fever of 38.9 ~ C for 1 month. Sub- acute bacterial endocarditis (SBE) could not be documented at a local hospital, but an echocardiogram showed mitral valve prolapse. In September, 1978, she developed an extensive pmfitic eruption. She was treated with topical fluorinated corticosteroids with slight improvement. She was admitted to Ohio State University hospitals for evaluation of the rash on April 9, 1979. She denied photosensitivity. Physical examination revealed a thin white woman in no acute distress with blood pressure of 120/80 mm Hg, pulse rate, l l0/min, respirations, 20/rain, and temperature, 37.2 ~ C. The skin revealed a raised, erythematous, serpiginous eruption with advancing borders, central clearing, and slight scale which involved the face, neck, trunk, and extremities. Slight vesiculation was noted at the edge of a lesion on the abdomen. Heart sounds were normal with a II-III/VI systolic ejection murmur at the left sternal border. No diastolic murmur or click was appreciated. There was no hepatospleno- megaly, and no other physical stigmata of SBE were present. CompLete blood cell (CBC) count disclosed hematocrit of 29.0%, hemoglobin, 9.4 gm/dl, white blood cell (WBC) count of 4,100/mm 3, with 14% bands, 68% PMN, 17% lymphocytes, 1% monocytes, and 335,000 platelets/mm ~. One week later the WBC count was 2,600/mm z. Erythrocyte sedimentation rate (ESR) was 36 (normal, up to 20). Antinuclear antibody (ANA) titer was positive at 1:160, speckled pattern. Lupus erythematosus (LE) cells were negative. Com- plement components were low: C'3,35 mg/dl (normal, 9%155), C'4, 3 mg/dl (normal, 13-44). Evaluation of renal status revealed normal electrolytes, blood urea nitrogen (BUN), i9 mg/dl (normal, 5-24), creafinine,

926 Camisa and Sharma Journal of the

American Academy of Dermatology

1.6 mg/dl (normal, 0.7-1.3), and urinalysis with 3+ protein, large (amount of) blood by dipstick, 5 WBC, 20 red blood cells (RBC), 10 hyaline and 4 granular casts per high-power field (HPF). Urinary protein excretion in 24 hours was 5,240 mg.

Skin biopsies for routine hematoxylin and eosin, periodic acid-Schiff, and mucin stains were taken from the leg and abdominal lesions. A specimen of uninvolved light-protected skin of the arm was obtained for direct immunofluorescence study. 2t She was treated with prednisone, 30 mg daily, and was readmitted for an open kidney biopsy in November, 1979. The BUN was 24 mg/dl, and the abnormal urinary sediment per- sisted.

In September, 1981, she presented to the emergency room with multiple painful vesicles on the dorsa of both hands, on the neck, and on the upper portion of the trunk (Fig. 1) related to a recent sun exposure. A skin biopsy was not performed at this time. CBC, BUN, and creatinine were within normal limits. The ESR was 24, C'3 52 mg/dl, and C'4, 9 mg/dl. The ANA was positive at 1 : 320 dilution with a diffuse pattern. The vesicular eruption gradually subsided during therapy, with prednisone 25 mg and hydroxychloroquine 400 mg daily. Repeat DIF on light-protected skin of the upper arm was performed in August, 1982.

Case 2

A 19-year-old black woman was well until May, 1979, when she complained of migratory joint pain of the wrist and ankles. Physical examination was normal with the exception of synovitis of the right ankle. She was treated with aspirin. Over the next 2 months she experienced increased joint pains, nausea, vomiting, weight loss, fatigue, and low-grade fever.

Laboratory data in September, 1979, revealed hemoglobin, 10.2 gm/dl, hematocrit, 29.7%, 3,900 WBC/mm ~, with a normal differential. ANA titer was positive at 1:320, diffuse pattern, and LE cells were positive. The ESR was slightly elevated at 34, and complement levels were depressed: C'3, 66 mg/dl (normal, 97-155), C'4, 6 mg/dl (normal, 13-44). Urinalysis was within normal limits. She was treated with hydroxychloroquine, 400 mg daily. In October, 1980, she developed painful oral ulcerations that resembled aphthae. Cultures for Candida and herpes simplex were negative. Evaluation of renal status showed BUN 11 mg/dl, creatinine, 0.9 mg/dl, and urinalysis with specific gravity, 1.022, pH 5.0, 3+ protein, large blood; 35 WBC and 4 RBC/HPF. Granu- lar but no cellular casts were present. Twenty-four-hour urinary protein excretion was 149 rag. In July, 1981, she was readmitted to Ohio State University hospitals.

Serum creatinine had risen to 2.0 mg/dl and hematoerit had dropped to 18%. Bone marrow examination confirmed that the anemia was due to "chronic disease." After receiving two units of packed RBC, a percutaneous biopsy of the right kidney was performed. Prednisone, 40 mg, and cyclophospharnide, 100 mg daily, was begun on Aug. 3, 1981. Two weeks later, after a recent sun exposure, she presented with a vesicular eruption. She noted a "burning" sensation in the lesions. Physical examination revealed multiple 3- to 6-mm clear tense blisters arising upon normal-appearing skin of the dorsa of the hands (Fig. 2) and ,arms, nose, and lips. Small circular or oval hypopigmented macules were also present on the arms and hands, but there was no evidence of scarring, milia formation, or nail dystrophy. A malar flush was present. The mucous membranes were clear. Creatinine had decreased to 0.9 mg/dl, but C'3 and C'4 remained markedly low. De- termination of 24-hour urinary excretion of uroporphy- rins and coproporphyrins was within normal limits. A shave biopsy of a blister from the left hand was exam- ined by light microscopy with hematoxylin and eosin, periodic acid-Schiff, and mucin stains. A punch biopsy of nonlesional buttock skin was studied for direct immunofluorescence.

Histopathologie findings Skin. Biopsies of lesions in Patients 1 (Figs. 3 and

4) and 2 showed similar changes: there were subepidermal blisters which contained PMN and microabscesses with nuclear "dus t" and fibrin deposition at the tips of the dermal papillae. An infiltrate consisting of PMN and nuclear "dust" was present in the upper interstitial dermis as well as around and within the walls of blood vessels of the superficial and mid-dermal plexuses, consistent with leukocytoclastic vasculitis. Eosinophils were rare. Free pigment was present in the superficial dermis in both cases. An additional biopsy from an urticarial lesion in Patient 1 without clinical vesiculation revealed essentially the same changes but presumably at an earlier stage in the evolution of the disease. The infiltrate of PMN was limited to the superficial dermis and vasculature, and leukocytoclasis was much less marked.

Alcian blue failed to reveal increased tissue mucin deposition nor was the PAS-positive basement membrane thickened in either case. In the vicinity of a blister, it was either indistinguishable or was found in the floor of the bulla.

Kidney, Both cases revealed a similar lesion by conventional light microscopy: diffuse mesangioproliferative glomemlonephfitis. Patient 2 showed the additional finding of segmental necrosis indicating " ac t i ve"

Volume 9 Number 6 December, t 983

Vesiculobultous systemic lupus elythematosus 927

Table I. Direct immunofluorescence studies on skin and kidney biopsies of patients with vesiculobullous SLE and mesangioproliferative glomerulonephritis*

Se,,I.a l I,,ate .,~ I i.o I c,3 1 F C 21 4/79 Non-sun-exposed + + + granular ND + + + granular ND

normal skin BMZ BMZ 8/82 Non-sun-exposed - + granular + + granular -

normal skin BMZ BMZ 1/79 Kidney + granular + granular + + + granular + granular

GBM GBM GBM, mesan- GBM

2 F B 19 8/81 Non-sun-exposed + + + granular + + granular normal skin BMZ BMZ

7/81 Kidney + + + diffuse + + granular granular GBM, segmental mesangium

gium

+ + + granular - BMZ - + + + dif-

fuse granular GBM, mesangium

BMZ: Basement membrane zone; GBM: glomerular basement membrane; ND: net done. *Intensity of immunofluorescence is graded from - to +++.

disease. Electron microscopic findings ~2 of deposits in the mesangium in both cases corroborate the light microscopic pictures of the lesions.

Immunofluorescence studies (Table I). Circulating BMZ antibodies were not found in either case by indirect immunofluorescence.

In all cases DIF revealed intensely positive granular staining for IgG and/or IgM at the BMZ. A weaker IgA band was present in Patient 2, but not studied initially in Patient 1. However, when DIF was repeated 28 months later in Patient 1 (after therapy with prednisone and hydroxychloroquine), lgA was indeed present, but IgG was now absent. With only one exception (IgM, Patient 2), when an immunoglobulin class was present in the skin, it was also found in the kidney. C'3 deposits were not found in any skin specimen but were found in both kidney biopsies.

DISCUSSION

We have presented two cases of SLE in which vesiculobullous eruptions occurred during a flare of systemic manifestations of the disease. The diagnosis of SLE is based on demonstrating four or more of the eleven 1982 revised criteria. 2a Case 1 had a positive ANA, persistent proteinuria greater than 0.5 gin/day, leukopenia, and photosensitivity. Patient 2 had a positive ANA and LE cell test, oral ulcerations, leukopenia, and photosensitivity. Both cases resemble DH histologically, with the exception that leukocytoclastic vasculitis is more marked than would be expected in DH. 24 The patients had clinical evidence of

renal disease documented by biopsy; the common lesion was diffuse mesangioproliferative glomerulonephritis. In Patient 2, IgA was present along with IgG and IgM at the BMZ by DIF. It was not looked for initially in Patient 1, but was present by repeat DIF over 2 years later when the vesicular eruption but not photosensitivity had resolved. In- terestingly, IgG was no longer a component of the DIF on uninvolved skin (lupus band test or LBT). The patient had been treated with prednisone and hydroxychloroquine, so we do not know whether IgA was present at the time of the kidney biopsy when vesiculobullous SLE was active. IgA was also a component of the LBT in all four of the cases reported by Hall et al. 2~ The finding of IgA at the BMZ, along with other immunoglobulin classes by DIF of other cases of vesiculobullous SLE reported in the literature, is summarized in Table II. The high incidence of IgA in these patients (64%) contrasts with the frequency of IgA in LBTs derived from series of patients with SLE in the literature (Table III), suggesting that vesiculobullous SLE is associated with deposits of IgA in lesional and nonlesional skin. Moreover, none of the reports listed in Table III describes a case of vesiculobullous SLE, and the incidence of this complication is certainly less than 13.3%. The high incidence of renal disease in patients with vesiculobullous SLE may not be remarkable since renal involvement may occur in 50% to 80% of patients with SLE. 25,2~

928 Camisa and Sharma


Dermatology

Table II. Summary of cases o f vesiculobullous SLE

Presence of IgA at BMZ of lesional or

Reference Cases nonlesional skin

1 1/1 Pedro and Dahl 3r (1973)

Renal disease (clinically

or histologically)

1/1

Davies et al 8 (1976) 1 1 / 1 1 / 1

Meyer et aP 5 (1976) 1 NS NS

Moncada 9 (1979) 1

Jacoby and Abraham ~6 (i 979) 1

Penneys and Wiley t5 (1979) 4

Hall et al 20 (1982) 4

Olansky et a133 (1982) 2

ND 1/1

0/1 1/1

1/3 2/3

4/4 3/4

0/2 1/2

Camisa and Sharma 2 2/2 2/2

Treatment/comment

Short trials with dapsone and sulfapyridine ineffective; cleared with prednisone Cleared with prednisone and dapsone Dapsone failed; systemic corticosteroids and azathioprine currently Cleared with prednisone and topical steroids Cleared with 60 mg prednisone daily Improved spontaneously or with prednisone Poor response to prednisone; dramatic response to dapsone Good response to prednisone and topical steroid or azathioprine Gradual clearing with systemic treatment of SLE and topical steroids

17 9/14 (64%) 12/15 (80%)

ND: Not done; NS: not stated in article.

T a b l e III. Frequency of IgA deposits in LBT of patients with SLE

No. I No. ,, cases IgA+ % Reference

42 4 9.5 Gilliam et al, 42 1974 24 0 0 Dantzig et al, 4z 1975 53 5 9.4 Wertheimer and Barland, 44

1976 39 7 17.9 Shrager and Rothfield, 28 1976 32 5 15.6 Morris et al, ~7 1979 88 16 18.2 Halberg et al, 45 1982

278 37 13.3

While IgA is an infrequent and when present, a nondominant component of the + L B T (Table III), there is some evidence to suggest that its presence is associated with disease activity. Morris et a127 noted that while there was no significant association of the class of immunoglobulin in skin or glomeruli with histologic type of glomerulone-

phritis, all five patients who demonstrated IgA in the LBT had decreased creatinine clearances com- pared to 22% of those without IgA. Schrager and Rothfield 2s found that IgA was absent in all nonlesional light-exposed skin of sixteen patients with SLE in remission and was present in seven of twenty-three patients with active disease, although not necessarily renal disease. Therefore, the increased incidence of IgA in LBTs of patients with vesiculobullous SLE may be explained by activity of the disease in skin as well as other organs.

There have been several case reports of subepidermal blisters occurring in association with SLE. ~9,a~ Vesiculobullous SLE is most often confused with bullous pemphigoid or dermatitis herpetiformis. While all three diseases have histo- pathologic features in common, immunofluorescence studies help to differentiate them. Circulat- ing BMZ antibodies are not detectable in all cases of BP. Moreover, the presence of antinuclear anti-


Vesiculobullous systemic lupus erythematosus 929

Fig. 1. Case 1, 1981. Photograph of subclavicular area demonstrates grouped vesicles in annular and arciform distribution. Fig. 2. Case 2, 1981. Demonstrates solitary and grouped tense blisters arising upon apparently normal skin of dorsum of hand. Fig. 3. Case 1, 1979. Photomicrograph shows subepidermal blister with collection of PMN at the tip of a dermal papilla. Clefts containing PMN can be seen forming at the left of the figure. (Hematoxylin-eosin stain; original magnification, x6.3.) Fig. 4. Case 1, 1979. Higher magnification of Fig. 3 identifies PMN, nuclear fragments, and fibrin-like material in a papillary microabscess. Early cleft formation is seen at the left. (Hematoxylin-eosin stain; original magnification, x 16.)

bodies may interfere with the detection of BMZ antibodies by standard technics when SLE and BP coexist . ~,31 Jordan et al 4 reported three cases of SLE with BP, two of whom were studied by direct and indirect immunofluorescence technics. Circu- lating BMZ and antinuclear antibodies were detected, and linear IgG staining was found at the

BMZ. None of the three responded to sulfapyridine or dapsone; one resolved spontaneously, and two responded to high doses of prednisone. More recently, a case of SLE with a generalized bullous eruption was described in which DIF of perile- sional skin revealed a tubular band at the BMZ staining for IgG, IgA, IgM, and C'3. 7 This pa-

930 Camisa and Sharma


Dermatology

tient's serum was positive for ANA and antibodies to Sm antigen, but circulating BMZ antibodies were not detected. A chronic cutaneous LE lesion from a pinna demonstrated a tubular band with IgG only. A fine linear tubular band with central absence of immunofluorescence as is seen in BP is differentiated from the broader granular, stippled, or homogeneous band at the BMZ found in SLE. a2

Immunoelectron microscopic studies have shown that the immune reactants in BP are located above the basal lamina in the lamina lucida; in SLE they are deposited in the upper dermis just beneath the basal lamina. Olansky et al aa confirmed the diagnosis of vesiculobullous SLE in two cases by demonstrating IgG deposits below the basal lamina by immunoelectron microscopy (IEM). The diagnosis of BP in the presence of SLE probably should not be made without the demonstra- tion of immune reactants in the lamina lucida. The previous reports of coexisting BP and SLE 4-7 must therefore be viewed with caution since IEM was not done.

A double immunofluorescence microscopic tech- nic was recently described which distinguishes diseases with immune deposits above and below the basal lamina, a4 The authors state that the method is technically easier, less time-consuming, and less expensive than IEM: it may be used as a rapid screening test if IEM is not available.

Meyer et al a5 recognized the problem of diag- nosing bullous diseases in patients with SLE. They described a 30-year-old man with SLE and a vesiculobullous eruption that mimicked DH histologically. The DIF was most consistent with SLE, but the immunoreactants are not specified in the article. The patient did not respond to dapsone, and the authors concluded that his skin disease was a manifestation of SLE. A report by Mon- cada 9 of DH in association with SLE is included in Table II as a case of vesiculobullous SLE because (1) the histopathology is compatible with either DH or SLE, (2) DIF revealed granular IgG at the BMZ of lesional skin (IgA was not tested), (3) the skin lesions cleared gradually with prednisone and topical steroids with no recurrences, and the patient was not treated with dapsone. The bullous dermatosis reported by Jacoby and Abraham a6 also probably represents vesiculobullous SLE. There were no immunofluorescence data to support a

diagnosis of either BP or DH. This patient's eruption did not respond to sulfapyridine but was well-controlled by prednisone. The patient reported by Davies et al s is included in the tabte because (1) leukocytoclastic vasculitis was noted in the skin biopsy, (2) DIF of lesional and nonlesional skin revealed granular IgG and IgM along with IgA at the BMZ, (3) a renal biopsy revealed mesangioproliferative glomerulonephritis, and (4) the renal and skin diseases were controlled with a combination of prednisone and dapsone.

Among cases originally reported as vesiculobullous SLE, one patient with a generalized eruption received brief therapeutic trials with dapsone and sulfapyridine because a skin biopsy was inter- preted as DH. a7 Both drugs had to be discontinued because of hematologic side effects. The blisters were controlled during therapy with prednisone. Penneys and Wiley 1~ reported four patients with SLE who presented with a vesiculobullous eruption that resembled DH clinically and histologically. Direct immunofluorescence of lesional and nonlesional skin demonstrated the typical findings of SLE. In all four cases, the cutaneous lesions developed during a flare of the SLE and improved either spontaneously or with oral prednisone as the activity of SLE in visceral organs subsided. No patient was treated with dapsone. By contrast, Hall et al 2~ recently reported four patients with vesiculobullous SLE in three of whom the eruption was not associated with a flare of the systemic disease. In all four, systemic manifestations of SLE improved with either prednisone or hydroxychloroquine while the skin diseases per- sisted. Subsequently, each patient enjoyed a dramatic response to dapsone (within 24 to 48 hours). Two of the four were able to discontinue dapsone without a recurrence. The authors also noted that IgA was no longer present in normal skin of two patients after therapy. This would be an unusual finding in DH, as whereas the dyna- mism of the LBT is well recognized, a'a

It should be emphasized that a subset of blistering eruptions that may occur in association with SLE has been described. Other distinct forms of bullous lesions in SLE, for example, vacuolar degeneration of the basal layer with dermal edema resulting in elevation of the epidermis 4~ or severe leukocytoclastic vasculitis] s may exist without


Vesiculobullous systemic lupus erythematosus 931

Table IV. Comparison of vesiculobullous SLE and DH

Vesiculobullous SLE DI-[

Clinical distribution Grouped or single vesicles and bullae

Symptoms

Histopathology

Direct immunofluorescence of uninvolved skin

anywhere, frequently sun-exposed areas Asymptomatic, pruritic, or "burning" Subepidemlal vesicles containing PMN and rarely eosinophils with microabscesses, nuclear "dust," fibrin at tips of dermal papillae; leukocytoclastic vasculitis in superficial and mid dermis frequently; vacuolar alteration of basal cell layer occasionally Granular IgG and/or IgM at BMZ in all cases; IgA also present in about 64% of all cases

Response of DIF to therapy Treatment

May change with activity of disease May resolve without specific therapy, or gradually as systemic disease responds to corticosteroids given for systemic effect, or dramatically to dapsone

Grouped papules, vesicles, and bullae on extensor surfaces, scapular area, buttocks, and scalp Usually intensely pruritic to "bum- ing" Subepidermal vesicles containing PMN and eosinophils in older lesions with micmabscesses, nuclear "dust," fibrin at tips of dermal papillael~'46; lymphocytes and PMN around blood vessels of superficial dermis

Granular IgA in dermaI papillae with fewer deposits beneath epidermal rete ridges in most cases; C3 also frequently found in same area 47 No change Dramatic response to dapsone or sulfapyridine

invoking an additional diagnosis of a primary bullous disease.

CONCLUSIONS

Two cases have been reported and cases re- viewed from the literature of SLE associated with vesiculobullous skin lesions. The cutaneous complication of SLE shares some clinical, histologic, and immunologic similarities with DH and may be confused with that entity. We believe that it represents a distinct subset of blisters that may occur in association with SLE and propose the following criteria for its diagnosis: (1) a diagnosis of SLE based on four or more of the American Rheuma- tism Association's fourteen preliminary criteria 4~ or of the eleven 1982 revised criteria'~a; (2) vesicles and bullae arising upon but not limited to sun-exposed skin; (3) histopathology compatible with D H (Table IV) and leukocytoclastic vasculitis in the superficial and mid dermis; (4) negative indirect immunofluorescence for circulating BMZ antibodies; (5) DIF of lesional and nonlesional skin always reveals linear or granular IgG and/or IgM and often IgA at the BMZ. If there is a

linear pattern of immunoglobulin deposition, immunoelectron microscopy should be done to dem- onstrate the immune reactants below the basal lamina. The spectrum of response to therapy for vesiculobullous SLE ranges from spontaneous clearing as the activity of the disease diminishes, to sluggish response to systemic corticosteroid and immunosuppressive therapy given for visceral manifestations of SLE, to dramatic clearing with dapsone.

AUTHORS' NOTE ADDED IN PROOF

Patient 1 was readmitted in August, 1983, because of fever, abdominal pain, and pancytopenia. Evalua- tion confirmed a flare of SLE, and the dose of prednisone was increased to 40 mg daily. All manifestations improved except for a subsequent flare of the vesiculobullous eruption. Dapsone, 50 mg daily, was started. The patient reported improvement of the rash within 72 hours and was free of vesicles and bullae after 1 week of therapy. Dapsone was discontinued after 2 weeks without a recurrence of skin lesions.

We acknowledge John C. Neff, M.D., for performing the inmaunofluorescence studies of skin, William

932 Camisa and Sharma Journal of the

American Academy of Dermatology

Roberts, M.D., for taking the photomicrographs, and Edmund D. Lowney, M.D. , for reviewing the manu- script.

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Vesiculobullous systemic lupus erythematosus

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I I I I I III Ill[ I I I II

A double-blind study of the effectiveness of a 3 % erythromycin and 5 % benzoyl peroxide combination in the treatment of acne vulgaris Dan K. Chalker, M.D . , * Alan Shalita, M.D. ,** J. Graham Smith, Jr. , M.D. ,*

and R. W. Swann, M.D.*** Augusta, GA, Brooklyn, NY, and Brunswick, GA

One hundred sixty-five subjects completed a 10-week, double-blind controlled study comparing the following: (1) a combination of 3% erythromycin and 5% benzoyl peroxide in a gel, (2) 5% benzoyl peroxide gel, (3) 3% erythromycin gel, and (4) the gel vehicle. The benzoyl peroxide gel and the erythromycin gel were superior to the control gel; however, the combination product was more effective than any of the others. This was ta-ue for both pustular and papular lesions, but the most dramatic effect was on combined inflammatory lesions, i.e., papules and pustules. (J AM ACAD DERNATOL 9:933-936, 1983.)

S y s t e m i c antibiotics for the treatment of acne v u l g a f i s have become an accepted therapeutic

From the Medical College of Georgia, Augusta,* and SUNY Downstate Medical Center, Brooklyn.**

Reprint requests to: Dr. Dan K. Chalker, Department of Dermatol- ogy, Medical College of Georgia, Augusta, GA 30912.

**,3215 Shrine Rd., Brunswick, GA 31520.

measure among dermatologists . In 1975 a review

of their use for ache vulgaris found them to be safe and effective. 1 Despite their safety, systemic antibiotics are not without side effects. ~-

Recently there has been increasing interest in the use of topical antibiotics. A number of these have been introduced and evaluated in clinical studies. These include: topical tetracycline, a-'~

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vesiculobullous systemic lupus erythematosus

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