IntroductionParaneoplastic pemphigus is an autoimmune disease associated with an underlying tumor. Several cases have been reported as unusual pemphigus vulgaris, erythema multiforme, or paraneoplastic bullous disease,1Anhalt G.J. Paraneoplastic pemphigus.Adv Dermatol. 1997; 12: 77-96PubMed Google Scholar but the incidence of the condition is unknown.2Cervini A.B. Tosi V. Kim S.H. et al.Case Report: Paraneoplastic Pemphigus or Paraneoplastic Autoimmune Multiorgan Syndrome. Report of 2 Cases in Children and a Review of the Literature.Actas Dermosifiliogr. 2010; 101: 879-886Crossref PubMed Scopus (13) Google Scholar Response to treatment is generally poor, with significant morbidity and mortality.This condition is clinically characterized by severe mucositis and polymorphic blistering skin eruptions, and histologically by acantholysis, keratinocyte necrosis, and interface dermatitis.3Mahajan V.K. Sharma V. Chauhan P.S. et al.Paraneoplastic Pemphigus: A Paraneoplastic Autoimmune Multiorgan Syndrome or Autoimmune Multiorganopathy?.Case Rep Dermatol Med. 2012; 2012: 207126Crossref PubMed Google Scholar Immunoprecipitation and immunoblot testing detect autoantibodies against desmosomal polypeptides.4Sehgal V.N. Srivastava G. “Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome”.Int J Dermatol. 2009; 48: 162-169Crossref PubMed Scopus (76) Google Scholar We describe a case of paraneoplastic pemphigus associated with an abdominal inflammatory myofibroblastic tumor in a 7-year-old girl.Case reportA previously healthy 7-year-old girl from the city of Valledupar, Colombia, presented to a different Institution in March 2009, with a 2-month history of severe depression, oral ulcers, denuded lips, and progressive bullae involving the face, extremities, and lower back and affecting 40% of her body surface (Figs 1 and 2). She had pemphigus vulgaris diagnosed by skin biopsy (Fig 3) and direct immunofluorescence and received treatment with oral prednisone, thalidomide, and azathioprine, with minimal improvement.Fig 2A, Finger. B, Soles.View Large Image Figure ViewerDownload (PPT)Fig 3Skin biopsy taken before treatment initiation shows acantholytic intraepidermal vesicular dermatitis suggestive of vulgaris pemphigus.View Large Image Figure ViewerDownload (PPT)In June of 2009, she was admitted to our hospital and received multidisciplinary treatment by pediatrics, pediatric dermatology, infectious disease, psychiatry, and endocrinology. Initial management included intravenous immunoglobulin, methylprednisolone, azathioprine, oxacillin, rituximab (4 doses), and psychotherapy. After 40 days of hospitalization, skin lesions partially improved. After discharge, prolonged courses of prednisone and continuous azathioprine temporarily controlled her disease. Cushing's syndrome, a small cataract, skin infections, and myopathy developed as side effects of therapy.Between April 2010 and July 2011, she required multiple hospitalizations for relapses and skin infections. In August 2011, she was seen in the emergency room for severe abdominal pain and fever. Salmonellosis was documented, and an abdominal ultrasound scan found a 55-mm vascularized mass in the right flank (Fig 4); biopsy of the mass showed an inflammatory myofibroblastic tumor (Fig 5).Fig 4Abdominal ultrasound scan shows a 55-mm, hypoechoic, solid mass with low resistance.View Large Image Figure ViewerDownload (PPT)Fig 5Biopsy of the abdominal mass found a fusocellular lesion associated with a mononuclear inflammatory infiltrate. A histologic diagnosis of an inflammatory myofibroblastic tumor was made.View Large Image Figure ViewerDownload (PPT)Surgical removal of 95% of the lesion was possible, with the remaining 5% adhered to the internal iliac vein. After surgery, the skin lesions began to improve and disappeared. At 4 years of follow-up, the residual tumor remains stable, and she remains asymptomatic without medications.DiscussionParaneoplastic pemphigus is a neoplasia-associated autoimmune disease, first described by Anhalt et al,5Anhalt G.J. Kim S.C. Standley J.R. et al.Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia.N Engl J Med. 1990; 323: 1729-1735Crossref PubMed Scopus (889) Google Scholar characterized by the production of autoantibodies against a complex of desmosomal proteins (desmoplakin I and II, bullous pemphigoid antigen 1, envoplakin, periplakin and desmoglein).6Ohyama M. Amagai M. Hashimoto T. Nousari H.C. Anhalt G.J. Nishikawa T. Clinical phenotype and anti-desmoglein autoantibody profile in paraneoplastic pemphigus.J Am Acad Dermatol. 2001; 44: 593-598Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 7Schepens I. Jaunin F. Begre N. et al.The protease inhibitor alpha-2-macroglobulin–like-1 is the p170 antigen recognized by paraneoplastic pemphigus autoantibodies in human.PLoS One. 2010; 5: e12250Crossref PubMed Scopus (77) Google ScholarParaneoplastic pemphigus is mainly associated with lymphoproliferative disorders such as non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Castleman's disease. Nonlymphoid malignant neoplasms, such as benign thymomas,8Hartz R.S. Daroca P.J. Clinical-pathological conference: cutaneous paraneoplastic pemphigus associated with benign encapsulated thymoma.J Thorac Cardiovasc Surg. 2003; 125: 400-406Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 9Leyn J. Degreef H. Paraneoplastic pemphigus in a patient with a thymoma.Dermatology. 2001; 202: 151-154Crossref PubMed Scopus (21) Google Scholar poorly differentiated sarcomas, and carcinomas of the lung, colon, pancreas,10Matz H. Milner Y. Frusic-Zlotkin M. Brenner S. Paraneoplastic pemphigus associated with pancreatic carcinoma.Acta Derm Venereol (Stockh). 1997; 77: 289-291PubMed Google Scholar and cervix11Chorzelski T. Hashimoto T. Maciejewska B. Amagai M. Anhalt G.J. Jablonska S. Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis, and bronchiolitis obliterans.J Am Acad Dermatol. 1999; 41: 393-400Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar are rarely associated.12Lemon M.A. Weston W.L. Huff J.C. Childhood paraneoplastic pemphigus associated with Castleman's tumour.Br J Dermatol. 1997; 136: 115-117Crossref PubMed Scopus (55) Google Scholar, 13Rodot S. Botcazou V. Lacour J.P. et al.Paraneoplastic pemphigus: review of the literature, apropos of a case associated with chronic lymphoid leukemia.Rev Med Interne. 1995; 16: 938-943Crossref PubMed Scopus (10) Google ScholarStomatitis is a cardinal feature and often the earliest presenting sign and is extremely resistant to therapy. Patients can present with vesicles, bullae, erosions, crusting, pruritic skin eruption resembling bullous pemphigoid,14Coelho S. Reis J.P. Tellechea O. Figueiredo A. Black M. Paraneoplastic pemphigus with clinical features of lichen planus associated with low-grade B cell lymphoma.Int J Dermatol. 2005; 44: 366-371Crossref PubMed Scopus (18) Google Scholar and erythematous papules with central vesiculation resembling erythema multiforme. Nikolsky sign can occasionally be seen.15Jansen T. Plewig G. Anhalt G.J. Paraneoplastic pemphigus with clinical features of erosive lichen planus associated with Castelman's tumor.Dermatology. 1995; 190: 245-250Crossref PubMed Scopus (67) Google Scholar Blisters and lichenoid lesions on the palms and soles, and pseudomembranous conjunctivitis, as in our patient's case, help to differentiate the condition from pemphigus vulgaris.16Allen C.M. Camisa C. Paraneoplastic pemphigus: a review of the literature.Oral Dis. 2000; 6: 208-214Crossref PubMed Scopus (45) Google Scholar The most commonly affected areas are the trunk, proximal extremities, head, and neck.17Robinson N.D. Hashimoto T. Amagai M. et al.The new pemphigus variants.J Am Acad Dermatol. 1999; 40: 649-671Abstract Full Text Full Text PDF PubMed Scopus (218) Google ScholarIn 1990, Anhalt et al5Anhalt G.J. Kim S.C. Standley J.R. et al.Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia.N Engl J Med. 1990; 323: 1729-1735Crossref PubMed Scopus (889) Google Scholar proposed diagnostic criteria (Table I), which Camisa and Helm18Camisa C. Helm T.N. Paraneoplastic pemphigus is a distinct neoplasia-induced autoimmune disease.Arch Dermatol. 1993; 129: 883-885Crossref PubMed Scopus (147) Google Scholar modified in 1993 (Table II).Table IOriginal diagnostic criteria for paraneoplastic pemphigus (Anhalt et al1Anhalt G.J. Paraneoplastic pemphigus.Adv Dermatol. 1997; 12: 77-96PubMed Google Scholar)1.Painful mucosal ulcerations and blisters and a polymorphous skin eruption in the context of an occult or known neoplasm2.Intraepidermal acantholysis, keratinocyte necrosis, and vacuolar interface changes in histopathology3.Deposition of IgG and complement C3 in intercellular epidermal and basement membrane zones seen on direct immunofluorescence4.Detection of serum autoantibodies to stratified squamous epithelia, columnar, and transitional epithelia by indirect immunofluorescence5.Serum immunoprecipitation of a characteristic complex of four proteins (250, 230, 210, and 190 kDa) from keratinocytes of transitional epithelia by indirect immunofluorescence Open table in a new tab Table IICamisa and Helm criteria for the diagnosis of paraneoplastic pemphigus11Chorzelski T. Hashimoto T. Maciejewska B. Amagai M. Anhalt G.J. Jablonska S. Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis, and bronchiolitis obliterans.J Am Acad Dermatol. 1999; 41: 393-400Abstract Full Text Full Text PDF PubMed Scopus (76) Google ScholarMajor Criteria1.Polymorphous mucocutaneous eruption2.Concurrent internal neoplasia3.Characteristic serum immunoprecipitation findingsMinor Criteria1.Positive cytoplasmic staining of rat bladder by immunofluorescence2.Intercellular and basement membrane zone immunoreactants on direct immunofluorescence of perilesional tissue3.Acantholysis in biopsy specimen from at least one anatomic site of involvement Open table in a new tab The course of Paraneoplastic pemphigus does not necessarily parallel the course of the underlying neoplasm. This condition can be associated with pulmonary disease including bronchiolitis obliterans and IgG deposits in respiratory epithelium, which in some cases may lead to respiratory failure accounting for the mortality cause in these patients.19Lane J.E. Woody C. Davis L.S. Guill M.F. Jerath R.S. Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) in a child: case report and review of the literature.Pediatrics. 2004; 114: e513-e516Crossref PubMed Scopus (35) Google Scholar, 20Takahashi M. Shimatsu Y. Kazama T. Kimura K. Otsuka T. Hashimoto T. paraneoplastic pemphigus associated with bronchiolitis obliterans.Chest. 2000; 117: 603-607Crossref PubMed Scopus (50) Google ScholarInflammatory myofibroblastic tumors are rare neoplastic lesions that occur primarily in children and young adults.21Coffin C.M. Watterson J. Pries J.R. et al.Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases.Am J Surg Pathol. 1995; 19: 859-872Crossref PubMed Scopus (1271) Google Scholar They may present in any organ, most often seen in soft tissues, lungs, and abdomen.22Coffin C.M. Humphrey P.A. Dehner L.P. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathologic survey.Semin Diagn Pathol. 1998; 15: 85-101PubMed Google Scholar These tumors were considered to have a benign clinical course, but now it is recognized that they can have an aggressive behavior and occasionally an unfavorable prognosis.23Meis J.M. Enzinger F.M. Inflammatory fibrosarcoma of the mesentery and retroperitoneum. A tumor closely simulating inflammatory pseudotumor.Am J Surg Pathol. 1991; 15: 1146-1156Crossref PubMed Scopus (416) Google Scholar Few cases of paraneoplastic pemphigus associated with inflammatory myofibroblastic tumors have been reported,24Lee D.H. Lee S.H. Sung J.K. Inflammatory Myofibroblastic Tumor on Intercostal Nerve Presenting as Paraneoplastic Pemphigus with Fatal Pulmonary Involvement.J Korean Med Sci. 2007; 22: 735-739Crossref PubMed Scopus (9) Google Scholar none in children. The tumor can be locally recurrent and rarely metastasizes. In most cases, complete surgical resection of the lesion is curative.Although paraneoplastic pemphigus is rare in childhood and adolescence, it should be included in the differential diagnosis of periorificial erosive dermatitis. Lesions that are refractory to therapy should prompt an aggressive search for a possible occult neoplasm with imaging of the chest, abdomen, and pelvis. IntroductionParaneoplastic pemphigus is an autoimmune disease associated with an underlying tumor. Several cases have been reported as unusual pemphigus vulgaris, erythema multiforme, or paraneoplastic bullous disease,1Anhalt G.J. Paraneoplastic pemphigus.Adv Dermatol. 1997; 12: 77-96PubMed Google Scholar but the incidence of the condition is unknown.2Cervini A.B. Tosi V. Kim S.H. et al.Case Report: Paraneoplastic Pemphigus or Paraneoplastic Autoimmune Multiorgan Syndrome. Report of 2 Cases in Children and a Review of the Literature.Actas Dermosifiliogr. 2010; 101: 879-886Crossref PubMed Scopus (13) Google Scholar Response to treatment is generally poor, with significant morbidity and mortality.This condition is clinically characterized by severe mucositis and polymorphic blistering skin eruptions, and histologically by acantholysis, keratinocyte necrosis, and interface dermatitis.3Mahajan V.K. Sharma V. Chauhan P.S. et al.Paraneoplastic Pemphigus: A Paraneoplastic Autoimmune Multiorgan Syndrome or Autoimmune Multiorganopathy?.Case Rep Dermatol Med. 2012; 2012: 207126Crossref PubMed Google Scholar Immunoprecipitation and immunoblot testing detect autoantibodies against desmosomal polypeptides.4Sehgal V.N. Srivastava G. “Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome”.Int J Dermatol. 2009; 48: 162-169Crossref PubMed Scopus (76) Google Scholar We describe a case of paraneoplastic pemphigus associated with an abdominal inflammatory myofibroblastic tumor in a 7-year-old girl.