Pemphigus erythematosus in a five-year-old child
Carolyn B. Lyde, MD, Sue Ellen Cox, MD, and Ponciano D. Cruz, Jr., MD Dallas, Texas
A 5-year-old girl had pemphigus erythematosus based on clinical and immunohistologic cri• teria. The rare occurrence in childhood ofthe pemphigus group of disorders, and ofpemphi• gus erythematosus in particular, is discussed. We also review current knowledge concerning the delineation of the different pemphigus subsets and the treatment of pemphigus erythe• matosus. (J AM ACAD DERMATOL 1994;31:906-9.)
Wedescribe pemphigus erythematosus in a child. We also review the literature on the occurrence of the pemphigus group of disorders in childhood and discuss the relation between pemphigus erythema• tosus, pemphigus foliaceus, and lupus erythemato• sus.
CASE REPORT A S-year-old black girl had a blistering eruption 2 days after a dental procedure. The blisters were confined ini• tially to the face, butsoon involved her trunk and extrem• ities. Courses of oral antibiotics and topical steroids pro• duced only minimal improvement. There was no family history of a similar disorder. Examination revealed almost generalized erythema with scaling and erosions (Figs. 1 and 2). Several intact bullae were present on the trunk; there were no mucosal lesions. Bilateral cervical and occipital adenopathy was noted. A 3 mm punch biopsy specimen revealed acantholysis limited to the stratum granulosum (Fig. 3). A specimen from perilesional skin was obtained for direct immuno• fluorescence. The specimen showed IgG and C3 in the intercellular spaces of keratinocytes and a linear band of C3 at the epidermal-dermal junction. Indirect immunofluorescence documented the pres• ence of circulating antibody directed at intercellular ke• Fig. 1. Generalized eczematous plaques and erosions at ratinocyte substance on monkey esophagus at a titer of previous bullae sites. 1:2560. Repeat studies atanother laboratory found inter• cellular antibodies on monkey esophagus "weakly posi• tive" to a titer of 1:640, and intercellular antibodies on tigens were not detected on monkey or guinea pig guinea pig esophagus "strongly positive" to a titer of esophagus. A speckled-pattern of antinuclear antibodies 1:640. Antibodies against basement membrane zone an- on HEp-2 substrate was demonstrated by two laborato• ries at titers of 1: 360 and 1:80, respectively. Extractable nuclear antigen antibodies (i.e., Ro(SS-A], La[SS-B], From the Department ofDermatology, University ofTexas Southwest• ern Medical Center. UtRNP, and Sm) tested by Ouchterlony diffusion and Reprint requests: Carolyn B. Lyde, MD, Department of Dermatology, anti-native double-stranded DNA tested by Crithidia lu• University of Texas Southwestern Medical Center, 5323 Harry cilia assay were notobserved. Theserum factor VIII level Hines Blvd., Dallas, TX 75052-9069. was 105% of normal. Magnetic resonance imaging did Copyright @ 1994 by the American Academy of Dermatology, Inc. not demonstrate abnormal mediastinal masses. 0190-9622/94 $3.00 + 0 16/4/57953 A diagnosis of pemphigus erythematosus was made, 906 Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2 Lyde et al. 907
Fig. 2. Close-up view of flaccid bullae.
Fig. 3. Hematoxylin-eosin stain shows superficial acantholysis consistent with either pem• phigus foliaceus or pemphigus erythematosus.
and the child was treated with oral prednisone (l mgj culating antibody directed at intercellular kerati• kg/day) and dapsone (50 mgjday). The cutaneous nocyte antigen) and oflupus erythematosus (malar lesions gradually resolved during thenext 2 months,leav• eruption, complement deposition in epidermal-der• ingonlymalarscalingwithminimalunderlyingerythema. mal junction, and positive antinuclear antibodies). Thedose ofprednisone was slowly reduced while thedose The paucity of children with pemphigus erythe• ofdapsone was increased to 75 mgjday. There have been matosus makes it difficult to predict a prognosis in no signs or symptoms of systemic lupus erythematosus during the 2 years of follow-up. our patient. She responded well to prednisone in combination with dapsone. Basset et al. I reported dapsone therapy to be helpful in five of nine adults DISCUSSION with superficial pemphigus. Patients with lower A diagnosis of pemphigus erythematosus was titers of circulating antibody had better response. madein our patientbased on theconcurrentfeatures Dapsone was discontinued in one responder because of pemphigus (flaccid bullae, acantholysis, and cir- ofhemolytic anemia and hepatotoxicity. Ithas been Journal of the American Academy of Dermatology 908 Lyde et al. November 1994
Table I. Distinguishing features of pemphigus variants
______1 Oinical features Acantholysis Antigen Superficial Foliaceus No mucous membrane involvement Subcorneal Desmoglein (160 kd) Erythematosus Overlapping features with lupus erythematosus Subcorneal ND Suprabasal Vulgaris Mucous membrane involvement Suprabasal Pemphigus vulgaris antigen (130 kd) Vegetans Vegetative lesions Suprabasal ND
ND, Not determined.
Table II. Reported cases of pemphigus erythematosus in children
Features of pemphigus Features of lupus erythematosus
Orculating Antibody antibody directed at Immunoreactants deposits between interceDular keratinocyte in epidermal- Authors Bullae Acantholysis keratinocytes antigen Malar eruption dermal junction ANA Richter21 (1950) + NR NR NR + NR NR (Cites Sakagami, 1923) Richter21 (1950) + NR NR NR Initial NR NR (Cites Klaber, 1937) Petratos and Andrade18 + + NR NR Widespread NR NR (1967) Beutner et a1. 22 NR NR NR NR NR NR NR (1973) Kowalska et a1. 2O + + IgG 1:160 + NR NR (1975) Igarashi et a1. 24 NR + IgG 1:64 NR NR NR (1980) Present case + + IgG 1:2560 Initial C3 1:80 (1994)
LE, Lupus erythematous; NR, not reported; +, present. speculatedthatdapsone exertsits therapeuticeffects existence. They described 11 adult patients with an by stabilizing lysosomal membranes, by inhibiting eruption ofseborrheic areas that consisted of malar cytotoxicity induced by polymorphonuclear leuko• lesions almost indistinguishable from lupus erythe• cytes, orbybothmechanisms. This explanation may matosus and of truncal lesions comprised of fragile be inadequate because polymorphonuclear cells do bullae similar to those in pemphigus vulgaris. In not predominate in primary lesions. Antimalarial 1968 Chorzelski et a1. 4 fueled renewed interest in agents have also been used for treatment of super• this disease by describing patients with the clinical ficial pemphigus. Hymes et a1. 2 reported hydroxy• features of the "Senear-Usher syndrome" and with chloroquine to be successful in treatment of three deposition of IgG and complement in both epider• patients with pemphigus foliaceus. Antimalarial mal intercellular areas and the epidermal-dermal agents quench oxygen radicals and can inhibit the junction. Similar patients, iricluding those with cir• formation of immune complexes. culating antinuclear antibodies, have since been de• Controversy exists with respect to the classifica• scribed byother authors. Most ofthese patients had tion ofpemphigus erythematosus. Oneview regards subclinical features of lupus erythematosus, al• it as a distinct entityin whichfeatures ofpemphigus though a few had full-blown systemic lupus erythe• and lupus erythematosus coexist. In 1925 Senear matosus.4-9 and Usher3 were the first to rePort this unusual co- Pemphigus erythematosus has also been consid- Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2 Lyde et al. 909 ered a variant ofpemphigus foliaceus. lO Pemphigus 2. Hymes SR, Jordon RE. Pemphigus foliaceus. Arch Der• encompasses a group of chronic blistering diseases matoI1992;128:1462-4. 3. Senear FE, Usher B. An unusual type of pemphigus com• characterized by the presence of circulating au• bining features of lupus erythematosus. Arch Dermatol toantibodies directed against desmosomal antigens Syph 1926;13:761-81. found in stratified squamous epithelia. Ithas been 4. Chorzelski T, Jablonska S, Blaszczyk M. Immunopatho• logical investigations in theSenear-Usher syndrome (coex• suggested that the four clinical types of pemphigus istence ofpemphigus and lupus erythematosus). Br J Der• (vulgaris, vegetans, foliaceus, and erythematosus) matoI1968;80:211-7. represent two basic categories; superficial pemphi• 5. N go AW, Straka C, Fretzin D. Pemphigus erythematosus: a unique association with systemic lupus erythematosus. gus and suprabasal pemphigus (Table 1).10,11 Cutis 1986;38:160-3. Evidence at the molecular level confirms pemphi• 6. Cruz PD Jr, Coldiron BM, Sontheimer RD. Concurrent gus foliaceus and pemphigus vulgaris to be dispar• features ofcutaneous lupus erythematosus and pemphigus erythematosus following myasthenia gravis and thymoma. atedisorders becausetheir respective autoantibodies JAM ACAD DERMATOL 1987;16:472-80. 12 14 bind to different desmosomal antigens. - Circu• 7. Krain LS, Bierman S. Pemphigus vulgaris and internal lating antibodies from patients with pemphigus fo• malignancy: a report offive cases. Cancer 1973;83:1091-9. liaceus coprecipitate a 160 kd glycoprotein that is 8. Orfanos CE, Gartmann H, Mohrle G. Zur Pathogenis des pemphigus erythematosus. Arch Dermatol Forsch 1971; identical to desmoglein, whereas circulating anti• 240:317-33. bodies from patients with pemphigus vulgaris iden• 9. Wieselthier JS, Treloar V, KohHK, et a1. Multiplecrusted tify a 130 kd glycoprotein. Each of these antigens plaques in a woman with systemic lupus erythematosus. Arch Dermatol 1991;127:1572-3. exists as a molecular complex with a common 85 kd 10. Perry RO. Pemphigus foliaceus. Arch Dennato11961;83: protein, called plakoglobin. 52-72. The true categorization ofpemphigus erythema• 11. Lever WF. Pemphigus. Medicine 1953;32:1·123. tosus might be resolved by characterization of the 12. Korman NJ. Pemphigus. Dermatol Clin 1990;8:689-700. 13. Eyre RW, Stanley JR. Human autoantibodies against a antigenic determinant(s) in this disease. If desmo• desmosomal protein complex with a calcium-sensitive glein proves to be the target of circulating anti• epitope are characteristic of pemphigus foliaceus patients. bodies in this disease, it would validate the notion of J Exp Moo 1987;165:1719.24. 14. Korman NJ, Eyre RW, Klaus-Kovtun V, et a1. Demon• pemphigus erythematosus as a variant ofpemphigus stration ofan adhering-junction molecule (plakog1obin) in foliaceus. the autoantigens of pemphigus foliaceus and pemphigus Pemphigus rarely occurs in children. Of the 55 vulgaris. N Engl J Med 1989;321:631-5. cases reported in children, 37 were diagnosed as 15. Kanwar AJ, Kaur S. Pemphigus in children. Int J Derma• tol 1991;30:343-6. pemphigus vulgaris, 1 as pemphigus vegetans, 11 as 16. Graff-Lonnevig V, Kaaman T. Juvenile pemphigus vul• pemphigusfoliaceus (excluding fogo selvagem), and garis. Acta Paediatr Scand 1991;80:262-5. 6 as pemphigus erythematosus. The diagnosis of 17. Andrade R. Pemphigus erythematosus in a six-year-old girl. In: Ruiz-Ma1donado R, ed. Modern problems in pedi• pemphigus erythematosus in these patients was atrics. Basel: Karger, 1975:190-2. based mainly (ifnot exclusively) on clinical features 18. Petratos MA, Andrade R. Pemphigus erythematosus. Am (Table II). 15-23 Indeed, even among the patients de• J Dis Child 1967;113:394-7. 19. Baer RL, Andrade R, SelmanowitzVJ. Pemphigus erythe• scribed after the advent of immunofluorescent matosus. Arch DermatoI1966;93:374-S. studies, none was shown to have laboratory features 20. Kowalska M, Blaszczyk M, Kupis B. Pemphigus erythe• of lupus erythematosus. Thus our patient represents matosus in an 8-year-old boy. Przeglad Derm 1975;62: theonlyfully documented case ofpemphigus erythe• 705-8. 21. Richter R. Das Senear-Usher Syndrom. Arch Dermatol matosus in childhood. Syph 1950;188:724-75. We thank Richard D. Sontheimer, MD, for advice in 22. Beutner ER, Chorzelski TP. Studies on etiologic factors in the preparation ofthis manuscript, and Ernst H. Beutner, pemphigus. J Cutan Pathol 1976;3:67-74. PhD, for confirmational serologic studies. 23. Smitt Sillevis JR, Mulder TJ, AlbOOa FW, et al. Pemphi• gus vegetans in a child. Br J Dermatol 1992;127:289·91. REFERENCES 24. Igarashi R, Morohashi M, Inomata N. An immunofluo• rescence studyoflight chain in pemphigus. Acta DermVe• 1. Basset N, Guillot B, Michel B, et al. 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