A 13-year-old boy comes to clinic having a 3-day history of swelling and redness of his eyes with discharge as well as pain with eye movement for 1 day. Acute bacterial conjunctivitis had been diagnosed elsewhere and topical antibiotic eye drops prescribed.Now he complains of inability to see with his right eye. In addition, he has had nonprojectile vomiting for 1 week and loose stools for 2 days, but no headache. He has had no fever, trauma, sick contacts, illicit drug use, polyuria, nocturia, or recent travel. He has gained 60 lb over the last 6 months despite normal activity. His grandparents have type 2 diabetes.Physical examination reveals a cooperative, obese teen who has a temperature of 98.7°F (37.1°C), heart rate of 110 beats/min, respiratory rate of 20 breaths/min, and blood pressure of 161/85 mm Hg. There is slight ptosis of the right upper lid, with lower lid chemosis and bilateral subconjunctival hemorrhage, more prominent on the right. The corneae and lenses are clear, and pupils are equally reactive bilaterally. Horizontal extraocular muscle movement is limited due to pain, with vertical movements intact. The optic discs appear normal. Visual acuity is 20/200 in the right eye and 20/20 in the left.His WBC count is 10×103/mcL (10×109/L), Hgb is 13 g/dL (130 g/L), Hct is 39% (0.39), and platelet count is 424×103/mcL (424×109/L). Electrolytes are within normal range. CT scan of the orbit is ordered, and an ophthalmologist is consulted.A 2-month-old infant girl is admitted to the hospital following 8 days of vomiting, diarrhea, and dehydration and is rehydrated intravenously. On day 2, a nurse notes a protrusion in the infant's neck when she cries.Physical examination reveals an alert, vigorous infant in no distress. Her temperature is 98.6°F (37°C), pulse is 164 beats/min, respirations are 40 breaths/min, and blood pressure is 72/30 mm Hg. The child has several abnormal features, including dolichocephaly (premature fusion of the sagittal suture), a large anterior fontanelle, a depressed nasal bridge, low-set ears, downslanting palpebral fissures, a high-arched palate, camptodactyly (permanent flexion of the fingers), and prominent calcanei.A dynamic bulge protrudes just left of the midline above the clavicle when the child cries. The mass does not appear on quiet breathing. The infant does not have increased work of breathing or tachypnea, and the remainder of the pulmonary and cardiac findings are normal. She has a reducible umbilical hernia. Her genitalia, muscle tone, and reflexes are normal.Chest radiograph and CT scan of the chest yield normal findings. Further radiologic studies reveal the diagnosisA 12-year-old boy is evaluated for oral ulcers, conjunctivitis, and a vesicular rash. Two weeks ago, he developed painful ulcers on his lips, tongue, and buccal mucosa. One week ago, he was given amoxicillin, but there was no improvement. Three days ago, his oral ulcers became so painful that eating and drinking became difficult. Yesterday he developed a pruritic, vesicular rash; conjunctivitis; and tactile fever. Three months ago, he had similar painful oral ulcers that resolved in 1 week. He has had no chronic illness, drug allergies, or recent contact with ill people.Physical examination reveals a thin, uncomfortable boy who has bleeding ulcerations on his lips. His temperature is 100.0°F (37.8°C), heart rate is 92 beats/min, respiratory rate is 24 breaths/min, and blood pressure is 131/72 mm Hg. Conjunctivae are erythematous, with yellow discharge bilaterally. He has white ulcerations on his buccal mucosa, gums, tongue, and lips, some of which are bleeding. A diffuse, clustered, vesicular rash on an erythematous base in various stages of healing is most prominent on his trunk, back, and genitalia. The rash is less pronounced on his face and extremities, with sparing of his palms and soles. His nasal mucosa is clear. The remainder of his physical findings are normal.On hospital day 2, he develops a dry cough. Chest radiograph is normal. Laboratory tests and a skin biopsy reveal the diagnosis.Possible diagnoses in a patient who has ptosis, eye swelling, pain, and sudden loss of vision include orbital cellulitis, carcinoma (primary or metastatic), retrobulbar abscess or hematoma, sarcoidosis, lymphoid tumor, Graves disease, optic neuritis, eosinophilic granuloma, and syphilis. The absence of fever in this patient argued against an acute infection. CT scan of the orbit showed preseptal soft-tissue stranding, with no focal abscess or hemorrhage. The orbital contents appeared intact and symmetric.Dilated eye examination showed sharp disc margins with an attached and well-perfused retina. Orbital pseudotumor was diagnosed. The patient was given high-dose prednisone, and his vision improved in 3 days without sequelae. His repeat blood pressure after pain medications was 122/84 mm Hg. Evaluation for autoimmune diseases was negative, but testing to explain his excessive recent weight gain showed dysmetabolic syndrome with insulin resistance. He was started on a regular exercise program, metformin, and diet monitoring to help with weight reduction.Orbital pseudotumor, also know as orbital inflammatory pseudotumor, is a rare, idiopathic, inflammatory process within the orbit. Some ophthalmologists prefer the term idiopathic orbital inflammatory syndrome. The condition is diagnosed by exclusion and affects adults primarily, with a 6% to 17% prevalence in children. Although usually unilateral in adults, orbital inflammatory pseudotumor commonly is bilateral in children. Because this disorder affects the vision, prompt diagnosis and referral to an ophthalmologist are crucial so treatment can be started immediately.Patients present with a sudden onset of pain, eyelid edema, proptosis, and subconjunctival hemorrhage, which may be associated with vision loss, photophobia, diplopia, ptosis, and motility restriction. Other potential findings include headache, vomiting, and weight loss, which are not seen in the adult population. Additional associations in pediatric patients include bilateral involvement, iritis, and a history of trauma preceding the inflammatory process.Another child who presented with a 3-week history of headaches and vomiting and had normal head CT scan results initially was believed to have migraine. She failed to respond to therapy with acetaminophen and propranolol and subsequently developed photophobia, diplopia, and eyelid swelling over 2 weeks. Orbital pseudotumor was diagnosed, and she was treated successfully with systemic corticosteroids.The cause of orbital pseudotumor is unknown. Several theories point to an immune-mediated mechanism causing inflammation, which compresses the orbital structures and results in a mass lesion effect. Infections and genetic and environmental factors also have been postulated. Histologic findings include a mixture of plasma cells, macrophages, eosinophils, mature lymphocytes, and polymorphonuclear cells. In some cases, increasing amounts of fibrovascular stroma are seen.Orbital pseudotumor is diagnosed clinically. However, because this condition presents with variable symptoms that may mimic other disorders such as orbital cellulitis or malignancy, orbital imaging is crucial. CT scan is the preferred imaging technique in the emergency setting because of its ease of use. On CT, orbital pseudotumor may demonstrate contrast enhancement and infiltration of orbital tissue, extraocular muscle enlargement, absence of contiguous paranasal sinus disease, and absence of bony erosion or distortion of orbital contents.Some authors prefer MRI to CT scan. MRI demonstrates hypointensity on T1-weighted images and isointensity or minimal hyperintensity on T2-weighted images. (1) The findings depend on the degree of fibrosis. For example, a lesser degree of signal intensity is seen with the sclerosis variety on T2-weighted images, but enhancement generally is increased after the introduction of gadolinium. (1)Some clinicians believe that evaluation of a patient who is suspected of having orbital pseudotumor should include CBC, absolute eosinophil count, electrolytes, ESR, anti-double-stranded DNA, antineutrophilic cytoplasmic antibodies, angiotensin-converting enzyme, rapid plasma reagin test, thyroid function studies, and serum electrophoresis.Oral systemic corticosteroids are the mainstay of treating orbital pseudotumor. Rapid response to steroids also is considered diagnostic. Prednisone 1 to 1.5 mg/kg per day (up to 100 mg/d) leads to resolution of pain and proptosis within 24 to 48 hours. Intravenous steroids should be reserved for patients who experience rapid progression of symptoms or vision loss.Low-dose radiotherapy has been used when corticosteroids fail or are medically contraindicated as well as during recurrences of signs and symptoms when the patient is receiving corticosteroid therapy. Surgery has been used to decompress localized tumors. Biopsy may be useful in evaluating patients who have presumed orbital pseudotumor, but because of the potential risk to surrounding orbital structures, surgery typically is not indicated.Orbital pseudotumor is a rare, benign inflammatory disorder of the orbit. The diagnosis is made by exclusion in patients presenting with eye pain, ptosis, chemosis, and vision loss. Findings on CT scan or MRI of the orbit, normal serologic test results, and a rapid response to steroids establish the diagnosis. Because this disorder affects vision, it is crucial to diagnose promptly and refer to an ophthalmologist for immediate treatment. (Mia Pingul, MD, Lopa Shah, MD, Scott Denton, MD, University of Nevada School of Medicine, Las Vegas, Nev.)Dynamic airway fluoroscopy demonstrated during a Valsalva maneuver that the mass was lung, establishing the diagnosis of a unilateral, apical cervical lung hernia. A search of the literature for a link between the patient's dysmorphisms and the cervical lung hernia failed to reveal an association. The family was reassured that the hernia should resolve eventually without intervention.Head and neck lesions are encountered commonly in newborns. The differential diagnosis can be extensive and includes both congenital and acquired conditions. History and physical examination can narrow the differential diagnosis and guide diagnostic testing. Pertinent historical and examination findings include the time when the mass initially was detected, location of the mass, presence of inflammation or drainage, color and character of the mass, transillumination, and the effect of a Valsalva maneuver on the mass. These findings guide further diagnostic efforts (TableT1).Branchial cleft cysts can present during the first year after birth. Improper branchial arch closure in early gestation results in a cleft cyst or sinus. Branchial cleft cyst can present as a nontender, fluctuant mass in the lateral anterior triangle. The cyst may become inflamed during an upper respiratory tract infection.Thyroglossal duct cyst presents as a painless mass that moves with tongue protrusion. Such cysts are found in the midline between the base of the tongue and the sternum, most often below the hyoid bone, and may become inflamed during an upper respiratory tract infection. Treatment of both thyroglossal duct cysts and branchial cleft cysts is excision following resolution of infection.Enlargement of the thyroid can be due to congenital goiter or a mass in the thyroid gland. Defects in fetal thyroxine synthesis or maternal antithyroid medications or iodides during pregnancy can cause congenital goiter. Congenital goiter always is present in congenital hyperthyroidism. Congenital goiter presents as thyroid enlargement (midline mass) at birth that may cause hyperextension of the head. Goiter nodules need nuclear medicine assessment for “hot” or “cold” status. Cold nodules must be evaluated further for malignancy. Treatment of goiters due to hypothyroidism requires immediate replacement of thyroid hormone.Lymphatic malformations, such as cystic hygroma, are congenital malformations of lymph tissue resulting from failure of the lymphatic primordial buds to establish venous drainage. A lymphatic malformation presents as a soft, smooth, nontender, compressible mass that transilluminates. Typically, lymphatic malformations fluctuate in size with infection or hemorrhage. These masses can cause respiratory compromise and difficulty feeding. Treatment of a lymphangioma is excision or observation, depending on the severity of the lesion.Hemangiomas are proliferative hamartomas of vascular endothelium that present at birth, grow rapidly during the first postnatal year, and begin to involute slowly by 18 to 24 months of age. Hemangiomas often present as red or bluish soft masses that enlarge with crying or Valsalva maneuvers and do not transilluminate. Surgery or laser therapy may be required if the hemangioma impinges on vital structures of the neck and chest.A laryngocele is an abnormal dilation or herniation of the saccule of the larynx. Laryngoceles may present in the newborn with hoarseness, stridor, cough, dyspnea, or dysphagia. They are found just lateral to midline and may enlarge with Valsalva maneuvers. Surgical excision is the management of choice.Congenital torticollis presents as a firm, painless, discrete, fusiform mass within the sternocleidomastoid muscle that slowly increases in size for 2 to 3 months and then regresses slowly for 4 to 8 months. Torticollis usually improves with conservative management, including stretching and exercises of passive and active range of motion.Lymphoma must be kept in mind when evaluating a neck mass.Cervical lung herniation is defined as the presence of lung tissue outside the confines of the bony thorax. Lung herniation was described first by Roland in 1499. Morel-Lavalee further classified lung hernias based on location and cause (intercostal, cervical, and diaphragmatic).Twenty percent of all lung hernias are congenital; the remainder follow trauma. Congenital cervical lung hernia manifests during the first year after birth but may not be apparent at birth. The most common location is cervical because of the absence or laxity of the endothoracic fascia (Sibson fascia) in this area.The presenting sign of a cervical hernia usually is a neck mass noticed while the patient is straining, crying, or coughing. Examination may demonstrate a supraclavicular mass that increases in size with Valsalva maneuvers, representing extrathoracic lung protrusion (Fig. 1). Cervical lung hernias are spongy and sometimes appear to move with respiration. They rarely are painful but may cause hoarseness, chronic cough, stridor, or superior vena cava syndrome by external compression of the structures within the neck. Of note, patients are at risk for pneumothorax when a central venous catheter is placed.Cervical lung hernias usually resolve spontaneously. Treatment should be pursued if there is incarceration or complications from compression of nearby structures.Although clinicians experienced in managing cervical lung hernias point out that their appearance usually is so characteristic that the diagnosis is apparent, clinicians should be aware of the wide spectrum of neck masses and the modalities available for differentiating among them. Imaging studies often are used to delineate the nature of a neck mass. Choice of the best study is guided by history and physical findings (TableT1). The most common modalities for evaluating neck masses include ultrasonography, CT, and MRI. Important factors guiding the choice of imaging include the size and suspected extent of the lesion, suspicion of vascular or airway involvement, need for a bedside examination, and the perceived risk of sedation.History and physical examination often allow the clinician to identify the nature of a congenital neck mass. Because the mass in this patient was dynamic, a dynamic study (airway fluoroscopy) was employed to verify the diagnosis. Although many types of neck masses occur in newborns and infants, masses that are intermittent are rare. The dramatic increase with Valsalva maneuver, absence of red or bluish color change, and supraclavicular location helped to focus the diagnosis. A cervical lung hernia should be considered when a neck mass behaves as this one did. (Elizabeth Walenz, MD, Michael Weisgerber, MD, Stephen Conley, MD, Children's Hospital of Wisconsin, Milwaukee, Wisc.)The differential diagnosis of mucocutaneous ulcers includes both infectious disorders (varicella zoster virus [VZV], herpes simplex virus [HSV]) and autoimmune conditions (Stevens-Johnson syndrome, toxic epidermal necrolysis, Behçet disease, lichen planus, pemphigus).Initially, the boy's condition was believed to be an infection. However, when he did not improve on antiviral therapy (intravenous acyclovir and trifluridine eye drops) and tests for infection were negative (negative direct fluorescent antibodies for VZV and HSV and negative viral cultures), a skin biopsy was performed. The biopsy showed acantholysis and deposition of immunoglobulin G (IgG) and C3 complement along the dermal-epidermal junction with direct immunofluorescence, findings consistent with pemphigus.Because pemphigus in children often is associated with an underlying neoplasm, CT scans of the chest, abdomen, and pelvis were performed, revealing a left perinephric mass measuring 7×5.2×7 cm and right lower lobe borderline bronchiectasis. The patient underwent a tumor resection and a left nephrectomy because the tumor was attached to the left kidney. Histologic examination revealed Castleman disease, a rare, benign, localized lymphoproliferative disease usually found in the retroperitoneum or mediastinum.In the hospital, the boy received immunosuppression with methylprednisolone, rituximab (monoclonal antibody against B cells), and daclizumab (antibody against interleukin-2 receptor), which resulted in improvement of his mucocutaneous lesions. Almost 1 year later, he continues to receive steroids and daclizumab and has had no recurrence of his mucocutaneous ulcers. No recurrence of his Castleman disease was noted on his most recent CT scan. However, he has progressive bronchiolitis obliterans, with worsening pulmonary function testing consistent with moderate obstructive pulmonary disease.Pemphigus is a term used to describe a group of autoimmune blistering diseases in which autoantibodies bind to the epidermis, leading to skin erosions. The three major types of pemphigus are pemphigus foliaceus, pemphigus vulgaris, and paraneoplastic pemphigus. The most benign variant is pemphigus foliaceus, in which IgG autoantibodies bind to the epidermis, leading to superficial erosions of the skin. In contrast, in pemphigus vulgaris, IgG autoantibodies bind to both the epidermis and epithelial lining of mucosal surfaces, leading to erosions in the skin, mouth, conjunctiva, nose, and genitalia. Pemphigus vulgaris is the most common type of pemphigus in adults and results in nearly 100% mortality if untreated and 5% to 25% mortality despite treatment.Although all three types occur in children, paraneoplastic pemphigus is the most common variant in this population and is associated with an underlying neoplasm, often Castleman disease. In paraneoplastic pemphigus, IgG autoantibodies bind to the epidermis and the epithelial lining of mucosal surfaces, including the respiratory epithelium, leading to erosions in the lungs in addition to erosions in the skin, mouth, esophagus, conjunctiva, nose, and genitalia. In addition, autoantibodies have been found in kidney, bladder, and striated and smooth muscle, leading some to suggest renaming the disease paraneoplastic autoimmune multiorgan syndrome (PAMS).In children, the mean age of presentation of paraneoplastic pemphigus is 13 years, with the youngest child presenting at 7 years. There is no sex predominance.The diagnosis of paraneoplastic pemphigus requires a high degree of suspicion in a child who has long-standing, painful oral ulcers, often the earliest and most consistent clinical finding. Some children do not have additional mucosal or cutaneous involvement. When cutaneous involvement does occur, eruption is highly variable and can present as lichenoid lesions, erythema multiformelike lesions, diffuse erythema, vesicobullous lesions, pustules, papules, or ulcerations potentially involving all areas of the skin, including the palms and soles (Fig. 2).Conjunctivitis and genital involvement are common. Esophageal and nasal erosions also may be present. Respiratory symptoms may be subtle initially, with children complaining of a dry cough but having a normal initial chest radiograph. However, respiratory involvement can progress to bronchiolitis obliterans, leading to severe chronic obstructive lung disease, the most common cause of death in this disease.Skin biopsy seeks to detect intraepidermal acantholysis and direct immunofluorescence staining. The specimen should be taken from noninvolved, perilesional skin. However, because there is a high false-negative rate for direct immunofluorescence staining in paraneoplastic pemphigus, serum also should be sent to a specialized laboratory for indirect immunofluorescence and immunoprecipitation studies.Diagnosis of paraneoplastic pemphigus requires identification of three major criteria or two major and two minor criteria. Major criteria include polymorphous mucocutaneous eruption, concurrent neoplasm, and a specific serum immunoprecipitation pattern. Minor criteria include histologic evidence of acantholysis, direct immunofluorescence with intercellular and basement membrane staining, and indirect immunofluorescence staining.Treatment of paraneoplastic pemphigus includes therapy for the underlying neoplasm as well as treatment of the autoimmune disease. In Castleman disease, resection often is curative. Unfortunately, resection of the underlying neoplasm does not halt progression of the autoimmune component of the disease in most cases, with a continued high mortality rate of approximately 90% from progressive respiratory involvement despite treatment. Optimal treatment for the autoimmune component of the disease is unknown. Immunosuppression (steroids, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil), targeted monoclonal antibody treatment (rituximab, daclizumab), plasmapheresis, and intravenous immunoglobulin all have been tried, but none has been found to be effective consistently.Paraneoplastic pemphigus should be considered in children who have severe, prolonged, painful oral ulcerations. Skin biopsy demonstrating acantholysis, characteristic direct immunofluorescence staining, serum immunoprecipitation, and indirect immunofluorescence staining help to make the diagnosis. Because the most common primary tumor associated with paraneoplastic pemphigus in children is Castleman disease, a CT scan of the chest, abdomen, and pelvis should be performed to search for an occult neoplasm. At least in some situations, early resection and immunosuppression may slow the development of bronchiolitis obliterans, the leading cause of death in children afflicted with paraneoplastic pemphigus. (Su-Ting T. Li, MD, MPH, University of California Davis, Sacramento, Calif.; Matthew C. Hollander, MD, Wright-Patterson Air Force Base, Ohio)