Paraneoplastic Autoimmune Multiorgan Syndrome (Paraneoplastic Pemphigus) in a Child: Case Report and Review of the Literature Joshua E. Lane, MD*; Carol Woody, MD*; Loretta S. Davis, MD*; Margaret F. Guill, MD‡; and Rita S. Jerath, MD§ ABSTRACT. Paraneoplastic autoimmune multiorgan bronchiolitis obliterans resulting in pulmonary de- syndrome, also known as paraneoplastic pemphigus, has struction and death. We report the case of a 10-year- been observed only rarely among children. We describe a old child who developed a diffuse mucocutaneous 10-year-old boy with typical clinical and histologic find- eruption that was clinically and immunopathologi- ings of paraneoplastic pemphigus associated with Castle- cally consistent with PAMS. Systemic evaluation re- man’s disease. His disease was refractory to resection of vealed a retroperitoneal Castleman’s tumor. the tumor and aggressive combination immunosuppres- sive therapies. The patient died 1 year after presentation, as a result of complications of bronchiolitis obliterans. CASE REPORT This case is unusual because of the young age of the A 10-year-old, previously healthy, white boy presented with a patient. Pediatrics 2004;114:e513–e516. URL: www. 2-month history of a papular eruption of the trunk, conjunctivitis, pediatrics.org/cgi/doi/10.1542/peds.2004-0436; paraneo- erosive stomatitis, proximal nail fold inflammation, and nail dys- plastic pemphigus, paraneoplastic autoimmune multior- trophy. Prior evaluation included a positive mycoplasma titer and a skin biopsy that was interpreted as indicating erythema multi- gan syndrome, child, Castleman’s tumor. forme/Stevens-Johnson syndrome. The mucocutaneous lesions were resistant to systemic corticosteroid treatment. The patient was referred to our institution because of progressive symptoms. ABBREVIATIONS. PAMS, paraneoplastic autoimmune multior- System review results included fever, cough for 6 to 8 weeks, gan syndrome; CT, computed tomography; C3, complement com- fatigue, constipation, and weight loss, with poor food intake at- ponent 3; Ig, immunoglobulin. tributable to painful oral ulcers. The physical examination re- vealed a thin boy with perioral cyanosis and resting tachypnea. A facial examination revealed bilateral exudative bulbar and palpe- araneoplastic autoimmune multiorgan syn- bral conjunctivitis, nasal septal erosions with crust, gray erythem- drome (PAMS) (paraneoplastic pemphigus) atous desquamation of the tongue and gums, and erosive ery- encompasses a multitude of mucocutaneous thema of the interdental gingiva (Figs 1 and 2). Erythematous P plaques were present on both palms, with erythema and edema of and systemic findings. Mucocutaneous involvement in paraneoplastic pemphigus is prominent, with the distal digits and dystrophic nail changes (Fig 3). In addition, an erythematous plaque with focal erosion was present on the painful erosive lesions involving the oral, nasal, up- glans penis. Pustules were present on the knees and ankles. Right per gastrointestinal, respiratory, ocular, and genital and left upper quadrant tenderness and fullness were noted in the epithelium.1 Cutaneous manifestations are variable abdominal examination. The initial differential diagnosis included and often consist of polymorphous inflammatory Reiter’s syndrome, Behcet’s disease, lupus erythematosus, der- matomyositis, and PAMS. macules, papules, and plaques. Histopathologic ex- Laboratory investigations revealed a normal complete blood aminations classically reveal acantholysis, intraepi- count, normal erythrocyte sedimentation rate (8 mm/hour), and dermal blister formation, and immunoreactant dep- negative titers for antinuclear antibody (Hep-2), anti-double- osition along the basement membrane and within stranded DNA, anti-SSA/Ro, anti-SSB/La, anti-Smith, anti-U1- epithelial intercellular spaces. Associated neoplasia ribonucleoprotein, anti-Jo-1, cytoplasmic anti-neutrophil cytoplas- mic antibody, perinuclear anti-neutrophil cytoplasmic antibody, is a requisite finding of PAMS but may be occult at anticardiolipin antibodies, cryoglobulins, HLA-B27, and HLA-B5. the onset of cutaneous lesions. Patients with PAMS Urinalysis results were normal. Chest radiograph results were frequently have significant pulmonary involvement, initially normal. which accounts for the high mortality rate. Histopathologic examinations of cutaneous biopsies demon- strated interface vacuolar dermatitis with minimal acantholysis, a The occurrence of PAMS in childhood has been slight increase in connective tissue mucin, and focal basement reported infrequently. When PAMS occurs among membrane thickening. The stratum corneum was compact and children, however, Castleman’s disease is the most parakeratotic. A specimen obtained after corticosteroid therapy common underlying neoplasm, with progressive showed vacuolar interface dermatitis with ulceration, acantholy- sis, abscess formation, and underlying vasculitis. No direct immu- nofluorescence was observed for immunoglobulin (Ig) G, IgA, IgM, or complement component 3 (C3). Indirect immunofluores- From the *Section of Dermatology, Department of Medicine, ‡Section of cence assays showed intercellular and dermal/epidermal staining Pulmonology, Department of Pediatrics, and §Section of Rheumatology, for IgG and C3 on monkey bladder (Fig 4). Paraneoplastic pem- Department of Pediatrics, Medical College of Georgia, Augusta, Georgia. phigus was diagnosed on the basis of clinical and histopathologic Accepted for publication May 19, 2004. findings. A neoplasm was not evident at that time. doi:10.1542/peds.2004-0436 Persistent constipation and the presence of abdominal fullness Address correspondence to Loretta S. Davis, MD, Section of Dermatology, prompted computed tomography (CT) evaluation of the abdo- Department of Medicine, Medical College of Georgia, 1004 Chafee Ave, men, which showed a mass (5.5 cm ϫ 7cmϫ 9 cm) in the right Augusta, GA 30912. E-mail: [email protected] lower retroperitoneal space. An open biopsy, complicated by sig- PEDIATRICS (ISSN 0031 4005). Copyright © 2004 by the American Acad- nificant bleeding, was interpreted as indicating a hemangioma. emy of Pediatrics. Magnetic resonance angiography was performed to delineate the www.pediatrics.org/cgi/doi/10.1542/peds.2004-0436Downloaded from www.aappublications.org/news byPEDIATRICS guest on September Vol. 25, 114 2021 No. 4 October 2004 e513 Fig 3. Prominent erythema and nail dystrophy of the distal dig- Fig 1. Exudative bulbar and palpebral conjunctivitis. its. blepharon as a result of chronic conjunctivitis, and he eventually lost his fingernails. Fourteen months after presentation, the patient’s lung function had progressively deteriorated. Chest CT scans showed new de- velopment of lower-lobe bronchiectasis, with progression of pre- viously identified, thin-walled, cystic lesions in both lungs and increasing areas of ground glass opacity, especially in the left lower lobe. Bronchoalveolar lavage was performed and showed no superficial inflammation or friability of the mucosa. Cultures were negative for bacterial, fungal, or viral infection. Sections from an open lung biopsy performed on the same day showed evidence of small-airway disease, with mucostasis and an absence of respi- ratory bronchioles in the visible sections. There was also mild cellular interstitial pneumonia, with small nonnecrotizing granu- lomas and multinucleated giant cells present, which was likely an incidental finding in the context of small-airway disease. Subse- quent CT scans of the abdomen and pelvis showed a residual tumor (2 cm ϫ 3 cm) inferior to the right kidney in the pelvis. One month after the lung biopsy, despite aggressive medical therapy, end-of-life issues needed to be discussed with the patient and his parents. The patient was discharged from the hospital with hos- Fig 2. Gray erythematous desquamation of the tongue and gums, pice care and died shortly thereafter. with mild nasal septal erosions and crusting. DISCUSSION An association between polymorphous skin le- vascular nature of the mass; it revealed a large feeding vessel to sions, including bullae, and internal malignancies the mass, which was embolized. has long been recognized. However, a distinct entity, Early in the disease course, the patient’s respiratory symptoms worsened. CT evaluation of the chest demonstrated a diffuse ie, PAMS (paraneoplastic pemphigus), was formally 1 interstitial infiltrate. The patient was unable to undergo pulmo- characterized by Anhalt et al in 1990, as an autoim- nary function testing because of the fixation of his mouth and mune bullous disease associated with neoplasia (of- painful oral lesions. A clinical diagnosis of bronchiolitis obliterans ten occult). The disease is typified by painful muco- was made. The patient was treated with prednisone (50 mg daily, sal ulcerations and polymorphous cutaneous lesions 2 mg/kg per day) and then intravenously administered ␥-globulin (24 g of Ig) and cyclosporine (350 mg/day). The skin findings progressing to bullae among patients with underly- transiently improved, except for those for the distal phalanges. ing neoplasia. Histopathologic findings include epi- Therapy with rituximab (monoclonal antibody against B cells) and dermal necrosis, acantholysis with suprabasilar cleft- daclizumab (antibody against interleukin-2 receptor) was subse- ing, vacuolar-interface changes (sometimes lichenoid quently initiated.2,3 Four months after presentation, the patient was referred to a inflammation), and exocytosis of inflammatory