EXPERIENCE AND REASON |
Pemphigus Vulgaris: The Eyes Have It
Department of Paediatrics
Hospital for Sick Children
University of Toronto
Toronto, Canada M5G 1X8
Division of Paediatric Medicine
Hospital for Sick Children
University of Toronto
Toronto, Canada M5G 1X8
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ABSTRACT |
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 TOP ABSTRACT CASE REPORTSDISCUSSIONREFERENCES |
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Pemphigus vulgaris is a potentially fatal autoimmune blistering disease that is rare in childhood. We report 2 recent cases seen contemporaneously in adolescents who presented with chronic oral mucosal lesions and conjunctivitis. The previously unemphasized ocular manifestations are described and the importance of a biopsy in establishing the diagnosis in instances of unexplained chronic mucositis is stressed.
Key Words: pemphigus • conjunctivitis
Abbreviations: PV, pemphigus vulgaris • IgG, immunoglobulin G • IV, intravenous
Pemphigus, derived from the Greek word meaning bubble or blister, refers to a group of uncommon autoimmune skin conditions characterized by blistering of the skin and mucous membranes. Before immunosuppressive therapy, pemphigus was usually fatal. Pemphigus is rare in childhood, and the diagnosis is usually not considered at the time signs first develop. We describe 2 adolescents with pemphigus vulgaris (PV) who presented with chronic mucositis and had conjunctival involvement before the development of cutaneous lesions, a feature unemphasized in the pediatric age group.
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CASE REPORTS |
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TOPABSTRACTCASE REPORTSDISCUSSIONREFERENCES |
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Case 1
A 15-year-old previously healthy boy of Pakistani descent was admitted to hospital in May 2001 because of a 2-month history of painful oral ulcers and conjunctivitis. The sores were noted to begin in the throat with progressive involvement of the lips, tongue, and buccal mucosa. He had no improvement after several courses of antibiotics prescribed by his family physician. Conjunctival injection with profuse watery discharge and photophobia began soon after the oral involvement, and the patient was ultimately admitted to the hospital because of severe dysphagia that precipitated a 5-kg weight loss. There was no history of fever, joint pain, abdominal pain, diarrhea, noticeable skin lesions, or exposure to medications before the onset of the lesions.
Physical examination revealed an unwell-looking boy. There were widespread erosions of the lips, gingiva, tongue, and buccal mucosa (Fig 1). Ophthalmologic examination revealed conjunctivitis. No uveitis was detected on slit-lamp examination, and visual acuity was normal. Three superficial erosions not previously noticed by the patient, measuring 0.5 to 0.8 cm in diameter, were seen on the trunk and scalp. An area of skin erosion was also seen on the corona of the penis. No vesicles or bullae were present.
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Laboratory investigations revealed a hemoglobin of 157 g/L, white blood cell count of 11.6 x 109/ L (5.35 x 109 /L polymorphonuclear leukocytes, 1.74 x 109 /L eosinophils) and a normal platelet count. The erythrocyte sedimentation rate was 9 mm/hour. Urinalysis, serum electrolytes, renal function tests, and transaminases were normal. Serology for antinuclear factor was negative. Viral studies of the oral lesions were negative for herpes simplex virus by polymerase chain reaction.
Total parenteral nutrition was provided because of severe dysphagia, and an intravenous (IV) morphine infusion was required for analgesia. Biopsy of one of the skin erosions was performed, demonstrating suprabasal and intraepidermal acantholysis with the formation of an intraepidermal, suprabasal vesicle. Immunofluorescence demonstrated intercellular deposition of immunoglobulin G (IgG) and C3, and serology for antidesmoglein 3 was positive by indirect immunofluorescence. The clinical, biopsy, and serologic findings were diagnostic of PV. Treatment with IV methylprednisolone (1 mg/kg/d) was administered for 2 weeks followed by prednisone 40 mg twice daily taken with calcium and vitamin D supplementation. Gradual improvement occurred over 3 weeks. One month after beginning treatment, all manifestations had resolved except for a persistent ulcerative throat lesion. Azathioprine was begun at 3 months as an adjunctive and steroid-sparing therapy.
Case 2
A 16-year-old previously healthy girl of African descent was admitted to hospital in June 2001 because of a 3-month history of painful oral ulcers that led to dysphagia precipitating a 9-kg weight loss and bilateral nonpurulent conjunctivitis. The sores began in the throat with progressive involvement of the lips, tongue, and buccal mucosa. She was unsuccessfully treated with 3 courses of oral antibiotics. There was no history of fever, joint pain, diarrhea, or exposure to medications.
Physical examination revealed bilateral conjunctival injection, and corneal ulcers were detected on slit lamp examination. Erosions were noted on the tongue, palate, and buccal mucosa. There were crusted lesions on the chest, shoulder, and thighs.
Biopsy of 1 of the skin lesions was performed, demonstrating intraepidermal bulla, spongiosis, and acantholysis. Serology was positive for circulating pemphigus autoantibodies in a dilution of 1:320. Immunofluorescence studies demonstrated IgG and complement deposition in the intercellular spaces in the epidermis. The clinical, biopsy, and serologic findings were diagnostic of PV.
She was treated with IV fluids and morphine for analgesia. IV methylprednisolone (1 mg/kg/d) was administered for 4 days, followed by prednisone (2 mg/kg/d).
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DISCUSSION |
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TOPABSTRACTCASE REPORTSDISCUSSIONREFERENCES |
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Pemphigus is caused by the formation of pathogenic autoantibodies directed against desmosomal proteins that act as intercellular adhesion molecules, leading to acantholysis or separation of epidermal cells from each other.1 Different forms of pemphigus occur, depending on the type of desmoglein attacked and the subsequent level of epidermis affected. PV is the most common form and presents with oral lesions and flaccid cutaneous blisters that may exhibit a Nikolsky sign, a separation of the epithelium with tangential pressure on the skin surface. Pemphigus foliaceous, a more benign form of the disease, involves the more superficial levels of the epidermis, presents with crusting skin lesions of the face, scalp, and upper trunk and rarely involves the mucous membranes. Desmoglein 3, present only in the deep epidermis, is affected in PV. Desmoglein 1, present throughout the epidermis, is the adhesion molecule affected in pemphigus foliaceous, and it is felt that the normal presence of desmoglein 3 in the deep epidermis compensates for the loss of desmoglein 1 in this condition and prevents deep skin and mucosal blistering.2 A paraneoplastic variant of the condition may occur, most commonly with lymphatic malignancies,3 and drug-precipitated forms (eg, penicillamine) have been reported. A transient neonatal form can occur in infants of affected mothers.4 Ocular manifestations may precede oral or skin lesions by several days to months. The characteristic ocular finding is conjunctivitis with hyperemia and mucoid discharge. Conjunctival blisters, erosions, and synechiae are rare, although conjunctival biopsies may demonstrate similar histopathologic and direct immunofluorescence findings to skin biopsies.5 The eye symptoms generally improve with the institution of systemic therapy, and long-term sequelae are uncommon.5 The few documented cases of ocular involvement in PV are in adults. To the best of our knowledge, ocular findings in pediatric PV have not been reported in the literature.
Pemphigus has a worldwide distribution but is more common among people of Ashkenazi Jewish and Mediterranean descent, affects both sexes equally, and has a mean age of onset in the sixth decade of life. Pemphigus is rare in childhood, and the diagnosis is usually not considered at the time signs first develop. Conditions that are commonly first considered include Stevens-Johnson syndrome, aphthous stomatitis, herpes simplex virus infection, impetigo, contact dermatitis, and Behcet’s disease. Other autoimmune disorders characterized by chronic oral mucositis include lichen planus, pemphigoid, linear immunoglobulin A disease, and epidermolysis bullosa acquisita.
The diagnosis of PV and the differentiation between it and other similar processes requires a biopsy of perilesional skin or oral mucosa. Immunoglobulin (usually IgG) and sometimes complement is detected by direct immunofluorescence in the intercellular spaces of the epidermis. Circulating autoantibodies can also be detected by indirect immunofluorescence testing of patients’ serum. The mainstay of treatment of PV is systemic steroid therapy in high doses (1–6 mg/kg/d). Adjuvant therapies have included azathioprine, cyclosporine, cyclophosphamide, methotrexate, dapsone, mycophenolate mofetil, plasmapheresis, and IV immune globulin.6
The course of PV in childhood is similar to that observed in adults and does not follow a more benign course as originally considered.7,8 Pemphigus is very uncommon in the pediatric population. These cases highlight the need to consider PV in children and adolescents with chronic mucositis without another obvious cause, the fact that PV may present with oral and conjunctival involvement before or without cutaneous signs, and the importance of a biopsy in establishing the diagnosis in cases of unexplained chronic mucositis.
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FOOTNOTES |
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Received for publication Oct 30, 2002; Accepted Jan 31, 2003.
Address correspondence to Michael Weinstein, MD, Division of Paediatric Medicine, Hospital for Sick Children, 555 University Ave, Toronto, Canada, M5G 1X8. E-mail: michael.weinstein{at}sickkids.ca
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REFERENCES |
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PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics
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