Markus D. Boos

Lipofibromatosis: an institutional and literature review of an uncommon entity.

We report six new cases of lipofibromatosis, an uncommon pediatric soft tissue neoplasm. This is the only series of patients to be described since the initial case series of 45 patients that characterized this entity in 2000. The purpose of this study was to characterize the presentation of lipofibromatosis to further define the clinical phenotype of this rare entity. Six patients were diagnosed with lipofibromatosis at our institution from 2000 to 2012. Patient age, sex, and ethnicity were recorded, along with tumor site and size, management, and recurrence data. Half of our patients were younger than 2 years old at presentation and the other half were school age. Boys and girls were affected with equal frequency. In five of six patients, lipofibromatosis presented in its “classic” form as a mass on the distal extremities. These tumors typically measured 1 to 2 cm in diameter, in contrast to case reports in the medical literature highlighting the occurrence of lipofibromatosis of greater size and at varied anatomic sites. The tumors in our series were managed using excision, with recurrence noted in 33%. Lipofibromatosis is an uncommon tumor typically found on the distal extremities of infants, although it can appear in various sizes and locations. It should be considered in the differential diagnosis of pediatric soft tissue neoplasms.

Atypical Cutaneous Blastomycosis in a Child With Juvenile Idiopathic Arthritis on Infliximab

Blastomyces dermatitidis is a dimorphic fungus endemic to much of North America, particularly the soils of the midwestern and southeastern United States. Human infection typically occurs through inhalation of airborne conidia, which can be followed occasionally by dissemination to the skin, bone, genitourinary system, and central nervous system. A hallmark of the pathogen is that it can cause disease in both immunocompetent and immunosuppressed populations. Blastomycosis is rare in pediatric patients, with cutaneous manifestations occurring even less frequently. Here, we report the case of a 9-year-old boy on iatrogenic immunosuppression with infliximab and methotrexate for juvenile idiopathic arthritis who presented with a nonhealing, indurated plaque of his right ear with significant superficial yellow crusting in the absence of constitutional symptoms. After failing a prolonged course of topical and oral antibiotic therapy, biopsy and tissue culture revealed Blastomyces dermatitidis infection. The area cleared after treatment with oral fluconazole and withdrawal of infliximab. To our knowledge, this is the first report of a pediatric patient developing an infection with B dermatitidis after initiation of therapy with a tumor necrosis factor-α inhibitor. This case also highlights an unusual morphology of cutaneous blastomycosis in an iatrogenically immunosuppressed child.

Experience with topical timolol maleate for the treatment of ulcerated infantile hemangiomas (IH)

To the Editor: Ulceration is the most common complication of infantile hemangiomas (IH). Oral beta-blocker therapy has been reported to be of benefit. Whether topical timolol maleate gelforming solution is appropriate treatment for ulcerated cutaneous IH remains controversial. We performed a retrospective case analysis evaluating adverse events from the use of timolol gelforming solution in treating ulcerated IH. After approval from the internal review board of the Children’s Hospital of Philadelphia, 30 children were identified from January 2009 to August 2014 with a diagnosis of ulcerated IH treated with timolol. Exclusion criteria included concomitant use of oral corticosteroids. Demographic information is listed in Table I. Table II illustrates that most patients were treated with 1 drop of timolol maleate 0.5% gel-forming solution twice daily. Most ulcers occurred in skin folds including the diaper area (30%), consistent with the existing literature. Ulcers ranged in documented size from ‘‘focal’’ to 3 cm. Timolol was applied for 5 to 345 days, with a median and mean

A Crusted Papule in a Premature Neonate

Amale neonatewas born at 25 weeks’ gestation by cesarean delivery because of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in his primigravid mother, who also had systemic lupus erythematosus managed with hydroxychloroquine, aspirin, and prednisone during pregnancy. The patient’s premature birth was complicated by acute respiratory distress that necessitated intubation and necrotizing enterocolitis that required parenteralnutrition.Atbirth, thepatientwasfoundtobemildly anemic (hemoglobin level, 11.0g/dL[toconvert tograms per liter, multiply by 10]) and thrombocytopenic (platelet count, 120 × 103/μL [to convert to 109/L,multiply by 1]) with concomitant intraventricular hemorrhage. Although afebrile, hewas treated empirically for sepsis with vancomycin hydrochloride and cefepime hydrochloride. A cerebrospinal fluid culture result was positive for Staphylococcus epidermidis, but the resultsofadditionalbloodcultureswerenegative fororganisms.Onday8afterbirth, a 0.5-cm, circular, crusted papule with a surrounding rim of erythema on the left hip was noted (Figure, A). A punch biopsy of the lesion was performed (Figure, B and C). Quiz at jamapediatrics.com A B

Pityriasis Lichenoides and Cutaneous T Cell Lymphoma: An Update on the Diagnosis and Management of the Most Common Benign and Malignant Cutaneous Lymphoproliferative Diseases in Children

Although more common with advanced age, the entire spectrum of benign and malignant cutaneous lymphoproliferative disorders can present in the pediatric population. Nevertheless, these conditions are often mistaken for other more common, benign dermatoses, resulting in delayed diagnosis. Standardized management of these conditions is also lacking. The purpose of this review is to provide an update on the most common benign and malignant cutaneous lymphoproliferative disorders in children: pityriasis lichenoides and mycosis fungoides. The presentation, evaluation and management of each of these conditions are discussed.

Degos disease mimicking primary vasculitis of the CNS.

A 4-year-old boy developed a headache. Initial evaluation revealed a normal neurologic examination and a right subdural hygroma on CT. Worsening headaches led to hospitalization at an outside institution. MRI showed leptomeningeal enhancement; magnetic resonance angiography (MRA) was normal. Infectious, rheumatologic, hematologic, and CSF studies were unrevealing. He then developed a left-sided hemiparesis. Imaging showed increased leptomeningeal enhancement with punctate infarcts in the right hemisphere. CT angiography demonstrated irregularity involving branches of the circle of Willis suggestive of vasculitis. Methylprednisolone (30 mg·kg−1·d−1 × 5 days) was administered for presumed CNS vasculitis.

Aquagenic wrinkling: A unique facial presentation

resulted from infliximab treatment; the other case was induced by etanercept. However, unlike the present case, erythroderma was not associated with the reported cases, which could explain why the pseudolymphomatous reaction resolved after withdrawal of the drug in both cases. Moreover, in the second case described, relapse did not occur after the administration of another TNF inhibitor, adalimumab. Because our patient developed an erythrodermic reaction, treatment with TNF inhibitors was halted. Cyclosporine was used as rescue therapy and resulted in dramatic improvement without any significant side effects.

Acute Onset of a Hemorrhagic Rash in an Otherwise Well-Appearing Infant

10-month-old, previously healthy girl presented withacute onset of a diffuse, hemorrhagic rash. Physicalexamination revealed multiple non-blanchable redplaques on her bilateral hands, feet, cheeks, and ears(Figure 1; and Figures 2 and 3; available at www.jpeds.com). A small red papule was present on the lower lip.Minimal edema of the hands and feet was also present, butno involvement of the conjunctiva, oropharynx, or othermucous membranes was noted (Figure 4; available at www.jpeds.com). The patient was well-appearing, playful, andafebrile, with stable vital signs.This patient had been treated 1 week prior for congestion,conjunctivitis, and otitis media with both moxifloxacin andamoxicillin/clavulanate.Shehadnohistoryofvomiting,diar-rhea, melena, or hematochezia. Urine dipstick was negativefor blood and protein.Thispatient’sclinicalpresentationwasconsistentwithadi-agnosis of acute hemorrhagic edema of infancy (AHEI), orFinkelstein’s disease. AHEI is a benign, small vessel vasculitischaracterizedbytheacuteonsetofhemorrhagic,targetoid,orrosette-shaped lesionsthat aremost commonlyfoundontheface, ears, and extremities.

Severe Mucha-Habermann-Like Ulceronecrotic Skin Disease in T-Cell Acute Lymphoblastic Leukemia Responsive to Basiliximab and Stem Cell Transplant

A 5‐year‐old girl with T‐cell acute lymphoblastic leukemia (T‐ALL) developed a progressive eruption of crusted papules and ulcerative plaques involving 80% of her body surface area with histopathology consistent with febrile ulceronecrotic Mucha–Habermann disease (FUMHD), although multiple specimens also contained clonal leukemic cells. Her skin disease was refractory to many classic treatments for FUMHD, including methotrexate, and became so severe that concern about superinfection prevented intensification of chemotherapy for her malignancy. The addition of basiliximab promoted gradual improvement of the skin, allowing for chemotherapy intensification and subsequent bone marrow transplantation, after which the eruption resolved completely. This report describes a severe case of FUMHD‐like eruption associated with clonal leukemic cells that improved with basiliximab, suggesting anti‐CD25 therapy as a novel treatment for ulceronecrotic skin disease in the setting of high interleukin‐2 levels.

A Progressive Blistering Eruption in a 5-Month-Old Male Infant.

DISCUSSION Bullous pemphigoid (BP) is the most common acquired autoimmune blistering disorder. It occurs primarily in elderly patients, aged 70 years or older, and classically presents as tense bullae on an erythematous or uninvolved base distributed on the trunk and proximal extremities. Accompanying intense pruritus is common. The appearance of BP can be protean, however, as excoriation can lead to linear and annular erosions. The condition can also manifest as urticarial papules and plaques, prurigo-like papulonodules, and eczematous lesions. A high degree of suspicion is required to make the diagnosis of BP in these instances. Involvement of the oral mucosa can also be seen in 10%–30% of patients, with involvement of other mucosal sites occurring less frequently. BP can also afflict infants and children. Although historically this was believed to be a rare occurrence, a recent study indicates that the incidence of infantile BP may be as high as 23:1,000,000 per year. Infantile BP (defined as BP present in children younger than 1 year) has a presentation unique from adult and childhood BP in that it primarily affects acral surfaces including the face. Generalized eruptions similar to that seen in our patient are also not uncommon in the infantile form of BP, although mucosal and genital involvement is rare. In contrast, mucosal and genital involvement is more frequent in children older than 1 year. In both infants and children, the disease appears to affect females with a slightly increased frequency. Although there are reports of infantile BP being triggered by vaccination, the majority of cases appear to be idiopathic in nature. The hallmark of BP is the production of autoreactive antibodies to the proteins BP180 and BP230. Although IgG is the primary isotype that appears to mediate disease, recent evidence implicates autoreactive IgE antibodies directed against BP180 in the pathogenesis of BP, as well. Various immune proteins and leukocyte subsets also appear to be required for the development of BP, including complement, mast cells, CD4+ T helper cells, and neutrophils. A diagnosis of BP requires histological and immunofluorescence studies to distinguish it from other blistering dermatoses. BP is characterized on histology by subepidermal bullae or papillary dermal edema with an associated eosinophilic infiltrate, although a variable neutrophilic or lymphocytic infiltrate may also be present. Direct immunofluorescence (DIF) performed on perilesional skin is a necessary confirmatory test and reveals linear staining of IgG and/or C3 at the dermal–epidermal junction (DEJ). At times, IgM, IgA, and IgE can also be seen. Other tests, such as indirect immunofluorescence or enzyme-linked immunosorbent assay to identify circulating anti-BP180 or anti-BP230 antibodies, are useful adjuncts when a diagnosis of BP remains in question. The differential diagnosis of infantile BP includes chronic bullous disease of childhood (CBDC), which is the most common bullous eruption in children. It usually presents around 5 years of age. Distinguishing CBDC from infantile or childhood BP on clinical grounds can be challenging, as CBDC is also characterized by red inflamed papules, vesicles, and bullae on erythematous or uninvolved skin. These lesions are commonly found on the lower abdomen, buttocks, and genitalia, although periorificial and mucous membrane involvement are also frequent occurrences. The bullae of CBDC are classically described as being arranged as a “cluster of jewels” or “string of pearls,” owing to their annular configuration, which can be a helpful clue to the diagnosis. Ultimately, however, the diagnosis of CBDC can only be made by histology, which shows subepidermal bullae with a predominantly neutrophilic infiltrate. CBDC is primarily an IgA-mediated disorder, and DIF accordingly demonstrates linear deposition of IgA at the DEJ. Other disease entities that should be considered in the differential diagnosis of infantile BP include epidermolysis bullosa acquisita and bullous lupus. These can typically be differentiated on histology within the appropriate clinical context. Bullous impetigo, herpesvirus infections, and an exuberant form of Hand, Foot, and Mouth disease caused by coxsackie A6 virus should also be considered in patients with widespread vesiculobullous eruptions. Bacterial and viral culture or polymerase chain reaction can help distinguish among these conditions. From the Department of Pediatrics, Section of Dermatology, The Children’s Hospital of Philadelphia, Philadelphia, PA. The authors declare no conflicts of interest. Reprints: Markus Boos, MD, PhD, Department of Pediatrics, Section of Dermatology, The Children’s Hospital of Philadelphia, 3550 Market Street, 2nd Floor, Philadelphia, PA 19104 (e-mail: boosm@email.chop.edu). Copyright