Pemphigus erythematosus

Background

This disease is also known as Senear-Usher syndrome and comprises 10% of cases. Like pemphigus foliaceus, it is a superficial variant of pemphigus and combines features of pemphigus and lupus erythematosus. It has erythematous, scaly plaques in a lupus-like butterfly distribution on the face as well as involving the scalp, back, chest, and intertriginous areas. Sunlight may exacerbate the disease. Like pemphigus vulgaris, there is association with other autoimmune disorders. Serologically, some patients may show ANA patterns suggestive of systemic lupus erythematosus.

Outline

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Senear-Usher syndrome

GEOGRAPHY

The incidence of pemphigus in the southern region of Saudi Arabia.

Tallab T, Joharji H, Bahamdan K, Karkashan E, Mourad M, Ibrahim K.

Department of Internal Medicine, College of Medicine and Medical Sciences, King Khalid University and Asir Central Hospital, Abha, Saudi Arabia.

Int J Dermatol 2001 Sep;40(9):570-2 Abstract quote

BACKGROUND: This is the first epidemiologic study of pemphigus in the southern region of Saudi Arabia.

METHODS: Data were collected from patient records in the outpatient and inpatient departments of Asir Central Hospital during the period 1990-99. The diagnosis of pemphigus was based on the clinical, histopathologic, and direct immunofluorescence patterns which were consistent with pemphigus.

RESULTS: The results showed that the mean incidence of the disease in the general population was 0.16/100 000; the mean incidence of the disease in the population above 20 years of age was 0.27/100 000. The prevalence of the disease at the end of the study period was 1.56/100 000 for the total population, and 2.7/100 000 for the population above 20 years of age. The male to female ratio was 2.2 : 1. The age of onset of the disease ranged from 23 to 67 years, except for one case at an age of 9 years, giving an average of 43.1 +/- 13.4 years and a median of 40 years. Pemphigus vulgaris was the most commonly encountered type, followed by pemphigus erythematosus (94.7% and 5.3%, respectively). Mucosal involvement occurred in 84.2% of cases. No association with neoplasia was found in the current study.

CONCLUSIONS: Pemphigus in the southern region of Saudi Arabia is as common as in other parts of the world, but with higher mucosal involvement.

DISEASE ASSOCIATIONS CHARACTERIZATION

PENICILLAMINE

Two cases of penicillamine-induced pemphigus erythematosus.

Thorvaldsen J.

Dermatologica 1979;159(2):167-70 Abstract quote

2 women, 62 and 69 years old, both suffering from rheumatoid arthritis, were treated for 1 and 1 1/2 years, respectively, with penicillamine. Both developed a bullous eruption which according to clinical and histological picture, immunofluorescence studies and to light provocation, as well as in 1 case to antinuclear antibody findings corresponded to pemphigus erythematosus.

In spite of treatment with prednisone and azathioprine, they still keep developing bullae.

SYSTEMIC LUPUS ERYTHEMATOSUS

Pemphigus erythematosus: a unique association with systemic lupus erythematosus.

Ngo AW, Straka C, Fretzin D.

Cutis 1986 Sep;38(3):160-3 Abstract quote

An association between pemphigus erythematosus and systemic lupus erythematosus is well recognized. However, most reports strongly imply that the clinical manifestations of lupus erythematosus are usually minimal or only serologically significant.

We describe the case of a 27-year-old black woman who experienced life-threatening systemic lupus erythematosus while recovering from pemphigus erythematosus. Unique histopathologic findings show the presence of both disorders in the same lesion.

THIOPRONINE

Pemphigus erythematosus induced by thiopronine.

Alinovi A, Benoldi D, Manganelli P.

Acta Derm Venereol 1982;62(5):452-4 Abstract quote

A patient affected by rheumatoid arthritis developed pemphigus erythematosus after 14 months of treatment with thiopronine. The lesions healed spontaneously after 4 weeks' withdrawal of the drug.

Whereas the pemphigus erythematosus induced by D-penicillamine is a quite rare but well documented side effect, we believe our case to be the first one reported as being due to thiopronine. It is very interesting to note that the two drugs are very similar with regard to chemical structure, mechanism of action, therapeutic indications and also side effects.

THYMOMA

Pemphigus erythematosus and thymoma.

Uhlin SR, Maiocco KJ, Bhatia SG.

Cutis 1980 Feb;25(2):177-9, 182 Abstract quote

A sixty year old woman was found to have a benign thymoma and pemphigus erythematosus. Her skin disease was controlled with oral and topical corticosteroids. The association between thymoma and pemphigus erythematosus is discussed, and the literature reviewed. Most previous cases have also had myasthenia gravis and skeletal muscle antibodies.

This is the first case in which neither of these was present.

Concurrent features of cutaneous lupus erythematosus and pemphigus erythematosus following myasthenia gravis and thymoma.

Cruz PD Jr, Coldiron BM, Sontheimer RD.

J Am Acad Dermatol 1987 Feb;16(2 Pt 2):472-80 Abstract quote

A case that exhibits the pathologic features of cutaneous lupus erythematosus and the immunopathologic characteristics of pemphigus erythematosus following myasthenia gravis and thymoma is presented, and the literature pertaining to these disease associations is reviewed.

The findings in this case were analyzed with respect to the accepted diagnostic criteria for lupus erythematosus, pemphigus, and pemphigus erythematosus. The pathogenic mechanisms that lead to acantholysis in pemphigus are examined in an attempt to explain why acantholysis did not occur in this case.

Pemphigus erythematosus associated with thymoma: a case report.

Fuxiang G, Beutner EH.

Department of Dermatology, Affiliated Drum Tower Hospital, Nanjing University College of Medicine, People's Republic of China.

Cutis 1999 Sep;64(3):179-82 Abstract quote

A 52-year-old Chinese man was found to have a benign thymoma and pemphigus erythematosus (PE). Initially, most of his skin lesions appeared on the scars of the surgical incisions and suture sites three months after he underwent thymectomy. To our knowledge, this is the first report documenting the skin lesions of PE on the scars after thymectomy.

Most of the previous cases had myasthenia gravis and skeletal muscle antibodies. However, in this patient, neither condition was present.

PATHOGENESIS CHARACTERIZATION

DESMOPLAKIN

Desmoplakin I and II in acantholytic dermatoses: preservation in pemphigus vulgaris and pemphigus erythematosus and dissolution in Hailey-Hailey's disease and Darier's disease.

Setoyama M, Choi KC, Hashimoto K, Ishihara M, Predeteanu GS, Dinehart S, Predeteanu C, Hamzavi LH, Etoh H.

Department of Dermatology and Syphilology, Wayne State University School of Medicine, Detroit, Michigan.

J Dermatol Sci 1991 Jan;2(1):9-17 Abstract quote

Desmoplakin I and II are important components of the attachment plaque of the desmosome which mediates cell to cell adhesion, in epithelial cells. In this study we used well-characterized antibody against desmoplakin I and II immunohistochemically and immunoelectron microscopically on two cases of pemphigus vulgaris and one case of pemphigus erythematosus and two cases each of Hailey-Hailey's disease and Darier's disease. In the normal human epidermis the desmosomes were demonstrated in a dotted pattern along cell periphery.

In pemphigus vulgaris and pemphigus erythematosus acantholytic cells and the perilesional cells exhibited normal dotted pattern along the cell periphery. In Hailey-Hailey's disease and Darier's disease, the dotted pattern is lost in acantholysed and perilesional areas and anti-desmoplakin I + II positive proteins were observed diffusely in the cytoplasm. Immunoelectron microscopical findings correspond to these light microscopical observations.

It is concluded that in autoimmune acantholytic disease such as pemphigus vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as Hailey-Hailey's disease and Darier's disease primary or secondary abnormalities abnormalities of desmosomes may be involved in their pathogenesis.

PE ANTIGENS

Regional variation in the expression of pemphigus foliaceus, pemphigus erythematosus, and pemphigus vulgaris antigens in human skin.

Ioannides D, Hytiroglou P, Phelps RG, Bystryn JC.

Department of Dermatology, New York University School of Medicine, New York, 10016.

J Invest Dermatol 1991 Feb;96(2):159-61 Abstract quote

The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was evaluated by indirect immunofluorescence by using sera with a high titer of PF, PE, and PV antibodies.

Regional variations were observed in the expression of all these antigens. The expression of the PF and PE antigens, as measured by endpoint titer of antibody reactivity, was highest in skin specimens obtained from the upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp.

This distribution pattern differed from that of PV antigen, whose expression was highest in buccal mucosa and scalp. These patterns correlate with, and may provide a partial explanation for, the different distribution of skin lesions in these different forms of pemphigus.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

LABORATORY MARKERS

SEROLOGY Shares identity to pemphigus foliaceus

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

CHILDHOOD

Pemphigus erythematosus in a five-year-old child.

Lyde CB, Cox SE, Cruz PD Jr.

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75052-9069.

J Am Acad Dermatol 1994 Nov;31(5 Pt 2):906-9 Abstract quote

A 5-year-old girl had pemphigus erythematosus based on clinical and immunohistologic criteria. The rare occurrence in childhood of the pemphigus group of disorders, and of pemphigus erythematosus in particular, is discussed.

We also review current knowledge concerning the delineation of the different pemphigus subsets and the treatment of pemphigus erythematosus.

PHOTODISTRIBUTION

Photo-induction of lesions in a patient with pemphigus erythematosus.

Deschamps P, Pedailles S, Michel M, Leroy D.

Photodermatol 1984 Feb;1(1):38-41 Abstract quote

Ultraviolet light applied to the normal appearing skin of a patient with pemphigus erythematosus produced clinical and histological changes, typical of the disease, in the irradiated skin. The action spectrum, studied with monochromatic light, was in the range of UVB.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL The histology is identical to pemphigus foliaceus with a subcorneal blister with acantholysis.

VARIANTS

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

DIRECT IMMUNOFLUORESCENCE Direct immunofluorescence shows intercellular and dermoepidermal staining for IgG and complement.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Pemphigus foliaceus

Pemphigus foliaceus: a case with serologic features of Senear-Usher syndrome and other autoimmune abnormalities.

Maize JC, Green D, Provost TT.

J Am Acad Dermatol 1982 Dec;7(6):736-41 Abstract quote

The two variants of superficial pemphigus, pemphigus erythematosus (Senear-Usher syndrome) and pemphigus foliaceus, share common histopathologic and indirect immunofluorescence findings. They differ in that pemphigus erythematosus is limited in distribution and usually has concomitant basement membrane zone deposition of immunoglobulin and complement in lesional skin in addition to intercellular space staining in the epidermis, whereas pemphigus foliaceus is a generalized process that reputedly lacks basement membrane zone staining.

A 49-year-old man with an array of immunologic abnormalities, including pernicious anemia and Sjogren's syndrome consistent with broad immunologic dysfunction, developed generalized superficial pemphigus (pemphigus foliaceus) with concomitant basement membrane zone immunoreactant deposition.

The demonstration of basement zone immunofluorescent staining lends additional support to the basic viewpoint that pemphigus erythematosus and pemphigus foliaceus are variable phenotypic expressions of the same basic disease process.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT Topical or oral corticosteroids

CYCLOSPORINE

The role of cyclosporine A in the treatment of pemphigus erythematosus.

Campolmi P, Bonan P, Lotti T, Palleschi GM, Fabbri P, Panconesi E.

Department of Dermatology, University of Florence, Italy.

Int J Dermatol 1991 Dec;30(12):890-2 Abstract quote

Steroids are effective in the autoimmune bullous disease pemphigus; however, treatment may be difficult to sustain because of severe side effects. Cyclosporine A acts mainly on helper/inducer T lymphocytes and has few side effects at low doses.

We report three patients with pemphigus erythematosus who had a relapse while receiving the maintenance dose of steroid therapy. All patients who were treated with both cyclosporine A (5 mg/kg/d) and prednisone (1 mg/kg/d) responded remarkably well to combined therapy. After clearing, prednisone was discontinued and cyclosporine A was reduced to 2 to 3 mg/kg/d.

With this treatment, all patients have been virtually free of symptoms, have remained well, and have had normal laboratory values.

Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

Commonly Used Terms

Pemphigus vulgaris.

Internet Links

Last Updated 1/25/2002

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Senear-Usher syndrome
GEOGRAPHY
The incidence of pemphigus in the southern region of Saudi Arabia. Tallab T, Joharji H, Bahamdan K, Karkashan E, Mourad M, Ibrahim K. Department of Internal Medicine, College of Medicine and Medical Sciences, King Khalid University and Asir Central Hospital, Abha, Saudi Arabia.	Int J Dermatol 2001 Sep;40(9):570-2 Abstract quote BACKGROUND: This is the first epidemiologic study of pemphigus in the southern region of Saudi Arabia. METHODS: Data were collected from patient records in the outpatient and inpatient departments of Asir Central Hospital during the period 1990-99. The diagnosis of pemphigus was based on the clinical, histopathologic, and direct immunofluorescence patterns which were consistent with pemphigus. RESULTS: The results showed that the mean incidence of the disease in the general population was 0.16/100 000; the mean incidence of the disease in the population above 20 years of age was 0.27/100 000. The prevalence of the disease at the end of the study period was 1.56/100 000 for the total population, and 2.7/100 000 for the population above 20 years of age. The male to female ratio was 2.2 : 1. The age of onset of the disease ranged from 23 to 67 years, except for one case at an age of 9 years, giving an average of 43.1 +/- 13.4 years and a median of 40 years. Pemphigus vulgaris was the most commonly encountered type, followed by pemphigus erythematosus (94.7% and 5.3%, respectively). Mucosal involvement occurred in 84.2% of cases. No association with neoplasia was found in the current study. CONCLUSIONS: Pemphigus in the southern region of Saudi Arabia is as common as in other parts of the world, but with higher mucosal involvement.

PATHOGENESIS	CHARACTERIZATION
DESMOPLAKIN
Desmoplakin I and II in acantholytic dermatoses: preservation in pemphigus vulgaris and pemphigus erythematosus and dissolution in Hailey-Hailey's disease and Darier's disease. Setoyama M, Choi KC, Hashimoto K, Ishihara M, Predeteanu GS, Dinehart S, Predeteanu C, Hamzavi LH, Etoh H. Department of Dermatology and Syphilology, Wayne State University School of Medicine, Detroit, Michigan.	J Dermatol Sci 1991 Jan;2(1):9-17 Abstract quote Desmoplakin I and II are important components of the attachment plaque of the desmosome which mediates cell to cell adhesion, in epithelial cells. In this study we used well-characterized antibody against desmoplakin I and II immunohistochemically and immunoelectron microscopically on two cases of pemphigus vulgaris and one case of pemphigus erythematosus and two cases each of Hailey-Hailey's disease and Darier's disease. In the normal human epidermis the desmosomes were demonstrated in a dotted pattern along cell periphery. In pemphigus vulgaris and pemphigus erythematosus acantholytic cells and the perilesional cells exhibited normal dotted pattern along the cell periphery. In Hailey-Hailey's disease and Darier's disease, the dotted pattern is lost in acantholysed and perilesional areas and anti-desmoplakin I + II positive proteins were observed diffusely in the cytoplasm. Immunoelectron microscopical findings correspond to these light microscopical observations. It is concluded that in autoimmune acantholytic disease such as pemphigus vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as Hailey-Hailey's disease and Darier's disease primary or secondary abnormalities abnormalities of desmosomes may be involved in their pathogenesis.
PE ANTIGENS
Regional variation in the expression of pemphigus foliaceus, pemphigus erythematosus, and pemphigus vulgaris antigens in human skin. Ioannides D, Hytiroglou P, Phelps RG, Bystryn JC. Department of Dermatology, New York University School of Medicine, New York, 10016.	J Invest Dermatol 1991 Feb;96(2):159-61 Abstract quote The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was evaluated by indirect immunofluorescence by using sera with a high titer of PF, PE, and PV antibodies. Regional variations were observed in the expression of all these antigens. The expression of the PF and PE antigens, as measured by endpoint titer of antibody reactivity, was highest in skin specimens obtained from the upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp. This distribution pattern differed from that of PV antigen, whose expression was highest in buccal mucosa and scalp. These patterns correlate with, and may provide a partial explanation for, the different distribution of skin lesions in these different forms of pemphigus.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
LABORATORY MARKERS
SEROLOGY	Shares identity to pemphigus foliaceus

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
CHILDHOOD
Pemphigus erythematosus in a five-year-old child. Lyde CB, Cox SE, Cruz PD Jr. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75052-9069.	J Am Acad Dermatol 1994 Nov;31(5 Pt 2):906-9 Abstract quote A 5-year-old girl had pemphigus erythematosus based on clinical and immunohistologic criteria. The rare occurrence in childhood of the pemphigus group of disorders, and of pemphigus erythematosus in particular, is discussed. We also review current knowledge concerning the delineation of the different pemphigus subsets and the treatment of pemphigus erythematosus.
PHOTODISTRIBUTION
Photo-induction of lesions in a patient with pemphigus erythematosus. Deschamps P, Pedailles S, Michel M, Leroy D.	Photodermatol 1984 Feb;1(1):38-41 Abstract quote Ultraviolet light applied to the normal appearing skin of a patient with pemphigus erythematosus produced clinical and histological changes, typical of the disease, in the irradiated skin. The action spectrum, studied with monochromatic light, was in the range of UVB.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL	The histology is identical to pemphigus foliaceus with a subcorneal blister with acantholysis.
VARIANTS

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
DIRECT IMMUNOFLUORESCENCE	Direct immunofluorescence shows intercellular and dermoepidermal staining for IgG and complement.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT	Topical or oral corticosteroids
CYCLOSPORINE
The role of cyclosporine A in the treatment of pemphigus erythematosus. Campolmi P, Bonan P, Lotti T, Palleschi GM, Fabbri P, Panconesi E. Department of Dermatology, University of Florence, Italy.	Int J Dermatol 1991 Dec;30(12):890-2 Abstract quote Steroids are effective in the autoimmune bullous disease pemphigus; however, treatment may be difficult to sustain because of severe side effects. Cyclosporine A acts mainly on helper/inducer T lymphocytes and has few side effects at low doses. We report three patients with pemphigus erythematosus who had a relapse while receiving the maintenance dose of steroid therapy. All patients who were treated with both cyclosporine A (5 mg/kg/d) and prednisone (1 mg/kg/d) responded remarkably well to combined therapy. After clearing, prednisone was discontinued and cyclosporine A was reduced to 2 to 3 mg/kg/d. With this treatment, all patients have been virtually free of symptoms, have remained well, and have had normal laboratory values.