A 43-year-old man with a history of anemia presented to the emergency department with a diffuse rash, which had been progressing for two months. He first developed painful bleeding ulcers in his mouth, then blisters on his trunk, extremities, and genitals. The blisters would rupture and bleed easily. He had lost 15 pounds since onset of the illness because of mouth pain while eating.
He also reported fevers and lethargy. He had no eye pain or vision changes and no family history of skin problems or malignancy. He had been sexually active with a single female partner, had no recent travel or sick contacts, and took no medications or supplements.
The patient's vital signs were within normal limits. An oral exam was significant for erosions and crusted lesions to the lips, tongue, and mucosa. The nostrils were involved, but the conjunctivae were normal. He also had flaccid bullae and scabbed lesions of varying sizes scattered over his trunk, flexural surfaces of the extremities, and groin. The margins of the blisters would extend when pressure was applied. The patient tested seronegative for HIV and syphilis. A complete blood count and basic metabolic panel were unrevealing.
What is the diagnosis? How would you treat this patient?
Find the diagnosis and case discussion on p. 12.
Diagnosis: Pemphigus Vulgaris
Pemphigus vulgaris (PV) is a mucocutaneous bullous autoimmune disorder in which antibodies to desmosomal proteins disrupt normal intracellular attachments. PV occurs primarily in middle-aged adults. (Clin Dermatol. 2011;29:432.) Exam findings include flaccid bullae scattered diffusely on the skin, extension of the bulla when pressure is applied (Asboe-Hansen sign), and shearing of the skin with rubbing (Nikolsky's sign). Mucosal involvement is common. (Lancet. 2005;366:61.) This is in contrast to bullous pemphigoid, which typically occurs in older adults with tense bullae, lacks mucosal involvement, and has a negative Nikolsky's sign. A thorough medication history helps distinguish PV from drug-induced pemphigus.
PV is ultimately diagnosed by clinical, histologic, immunopathologic, and serologic assessments. A punch biopsy taken from a new PV lesion will show suprabasal acantholysis and a pattern of the basal keratinocytes that resembles a row of tombstones. A direct immunofluorescence biopsy taken from normal-appearing skin shows deposition of IgG in the upper layers of the dermis. Indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) can also be used to support the diagnosis of PV. (Fitzpatrick's Dermatology in General Medicine Eighth Edition. New York: McGraw-Hill Education; 2012.)
Left untreated, the prognosis of PV is poor, with mortality higher than 70 percent within one to five years. (Lancet. 2005;366:61.) Oral glucocorticoids such as prednisone, prednisolone, or methylprednisolone are first-line therapy. The recommended starting dose of prednisone or prednisolone is 1-2.5 mg/kg per day. Steroids should be tapered once new skin lesions have stopped forming. (Br J Dermatol. 2017;177:1170; http://bit.ly/2Z9MrVk.)
Rituximab, a monoclonal antibody, can also be used in conjunction with steroids as a first-line agent, although it is costly and reserved for patients with severe or refractory disease. Rituximab has been shown to increase remission rates and reduce the steroids dose needed to induce remission of PV, reducing the side effects caused by glucocorticoids. (Lancet. 2017;389:2031; http://bit.ly/2ZeF4w4.) Nonsteroidal immunosuppressive agents such as azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide, and cyclosporine are typically used as adjuvants to steroids. These agents have not been found to increase the rate of remission, but they do reduce the glucocorticoid dose needed, a major benefit. (Br J Dermatol. 2017;177:1170; http://bit.ly/2Z9MrVk.)
Local wound care is important for reducing symptoms and preventing secondary infections. Topical corticosteroids can also be used for symptomatic treatment, and viscous lidocaine improves oral discomfort. Inpatient admission should be considered for patients with a new diagnosis of PV and large areas of skin or mucosal involvement or evidence of dehydration and electrolyte abnormalities.
Our patient was admitted for intravenous hydration and dermatology consultation. A biopsy with immunofluorescent staining and ELISA confirmed the PV diagnosis. He was started on prednisone 1 mg/kg per day with a plan to follow up with the dermatology clinic to start rituximab and mycophenolate mofetil pending infectious disease screening. His course was complicated by superinfection with HSV-1 and Staphylococcus aureus, requiring treatment with oral valacyclovir and dicloxacillin.
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Dr. Grzybowskiis a fourth-year emergency medicine resident at LAC+USC Medical Center. Dr. Burkholderis an assistant professor of clinical emergency medicine at the Keck School of Medicine at the University of Southern California. Follow him on Twitter@tayburkholder.