Acquired bullous diseases of childhood: re-evaluation of diagnosis by indirect immunofluorescence examination on 1 M NaCl split skin and immunoblotting

Summary Acquired autoimmune bullous diseases of childhood are rare, and can be difficult to distinguish clinically. We have studied 12 children, with an initial diagnosis of bullous pemphigoid (BP) in eight patients, cicatricial pemphigoid (CP) in one, chronic bullous disease of childhood (CBDC) in one, and epidermolysis bullosa acquisita (EBA) in two.
All patients had positive indirect immunofluorescence (HF) of the BMZ with IgG. Using 1 M NaCl split skin, six patients showed epidermal binding of IgG, with additional IgA in three cases, and in five patients IgG antibodies bound a dermal protein. Immunoblotting studies revealed an antibody to type VII collagen (EBA antigen) in three patients who had a dermal pattern on IIF. Six sera reacted with an epidermal protein of 180 and/or 220 kDa, characteristic of BP and CP. One of the three IgA-positive sera detected 220-and 180-kDa epidermal proteins using anti-IgA antibody. Following these studies the diagnosis was changed in three of the children. The diagnosis of CBDC was changed to either BP or EBA because of the presence of circulating IgG autoantibodies. In two children with an initial diagnosis of BP the diagnosis was changed to EBA.
We conclude that the clinical picture in bullous disorders of childhood shows considerable overlap, and is often misleading. Additional circulating IgA autoantibodies seem to be more common in BP than has been recognized previously. Indirect immunofluorescence investigation on 1 M NaCl split skin may be helpful in differentiating between BP and EBA, but does not replace immunoblotting studies. EBA is apparently more common in children than in adults. No difference was found between the children with BP and EBA with regard to the duration of disease. The long-term outlook is good, although the course may be protracted.     

Eruptive pseudoangiomatosis

We describe two children with acute onset and spontaneous resolution of angioma-like papules during a viral illness. The biopsy specimens from both patients showed a unique histologic appearance consisting of dilated dermal blood vessels with plump, hobnail-shaped endothelial cells. On the basis of the natural history and the histopathologic features we suggest the diagnosis of eruptive pseudoangiomatosis.     

Nevus of Ota in children

Nevus of Ota, synonymously termed oculodermal melanosis, is an uncommon dermal melanosis most commonly seen at birth in children of Japanese descent, though it can affect individuals of any age or ethnicity. The disease tends to persist and extend locally, becoming increasingly prominent with age, puberty, and postmenopausal state. Treatment should begin early after diagnosis using multiple sessions of laser photothermolysis to avoid darkening and extension of the lesion. Important associated disorders include ipsilateral glaucoma; intracranial melanocytosis; and rarely cutaneous, ocular, or intracranial melanoma. Recommendations are discussed for managing nevus of Ota in children.     

Balloon cell nevus in children: Report of three cases of the scalp and review

Balloon cell nevus (BCN) is a histopathological variant of cutaneous acquired melanocytic nevi characterized by junctional and/or dermal nests of large cells with a clear and foamy cytoplasm which has rarely been described in children. Three cases of BCN firstly reported on the scalp in two pediatric patients are presented along with a literature review. Dermoscopy is particularly indicated in those pigmented lesions showing a yellowish hue, in ruling out in real time those disorders that may clinically be similar such as xanthogranuloma and sebaceous nevus, and to suggest the diagnosis of BCN. The final diagnosis, however, is established by histopathological examination.     

Lymphomatoid papulosis in children: experience of five cases and the treatment efficacy of methotrexate

We present a case series of childhood lymphomatoid papulosis (LyP), an entity which is commonly misdiagnosed and poorly described in the paediatric dermatology literature. Clinically and histologically, the features of LyP in children can mimic insect bite reactions, with prominent dermal neutrophils and eosinophils. However, CD30 immunohistochemical staining of atypical lymphocytes within a mixed inflammatory infiltrate should point to the diagnosis of LyP. There is no consensus to guide management of childhood LyP due to its rarity and largely unknown natural course. We discuss our experience with LyP in five children and the use of methotrexate to induce rapid resolution of persistent lesions and to reduce recurrences in two children. Although none of our cases have experienced malignant transformation to date, life-long monitoring is advocated.     

Childhood bullous pemphigoid – report of a case with dermal fluorescence on salt-split skin

Summary Bullous pemphigoid (BP) is an acquired bullous disorder which predominantly affects the elderly. It is rare in children, and may be clinically indistinguishable from other immunobullous disorders. As routine histology may be non-specific, a definitive diagnosis of childhood BP usually depends on the results of direct and indirect immunofluorescence investigations.
We report a 5-year-old girl who developed bullous pemphigoid, associated with atypical immunofluorescence findings. Indirect immunofluorescence on split-skin showed a pure dermal pattern of IgG binding. This is usually suggestive of epidennolysis bullosa acquisit, but Western immunoblotting was positive with epidermal extracts, confirming a diagnosis of BP. Dermal binding on split-skin occurs in about 5% of adult cases of BP, and has not been reported previously in childhood BP.     

Linear IgA disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD285 and a dermal 180-kDa protein

BACKGROUND: Linear IgA disease (LAD) of adults and children is mediated by IgA antibodies that target proteins of the epithelial adhesion complex. Most studies have concentrated on the epidermal-associated antigens; the dermal antigens remain unresolved. OBJECTIVES: To determine the dermal antigen repertoire of IgA and IgG antibodies in LAD. METHODS: Immunoblotting was carried out on salt-split and urea-extracted dermal skin extracts with IgA antibodies (63 adult and 34 childhood sera) and with IgG antibodies (49 adult and 18 childhood sera). RESULTS: Antigens were identified by IgA (61%), IgG (27%) and by both antibody isotypes (19%). LAD285 and an antigen of 180 kDa were the major dermal antigens identified, and antigens of 230 kDa, collagen VII and a protein under 100 kDa were identified less commonly. IgA autoantibodies from adults bound single antigens more frequently than multiple antigens; from children they bound single and multiple antigens equally. The binding of multiple antigens was, however, more common in children than adults. The IgG response was weaker. The 180-kDa antigen was the main IgG dermal target, and with a single exception, IgG autoantibodies targeted single antigens. CONCLUSIONS: There was an IgA and IgG response to dermal antigens in LAD; however, the dual antibody response was limited. The antibody response to LAD285 and a 180-kDa antigen (probably BP180) suggests that intermolecular epitope spreading of the antigens associated with the extracellular matrix/dermal components of the basement membrane contributes to the immunopathology of the disease. The restricted IgG response suggests that dermal-binding IgG autoantibodies are not pathologically significant.     

Multicentric Reticulohistiocytosis: A Case Report of an Atypical Presentation in a 2‐Year‐Old

Multicentric reticulohistiocytosis (MRH) is a rare systemic inflammatory granulomatous disease marked by severe and often rapidly progressive polyarticular arthritis and cutaneous papulonodules. Initial clinical diagnosis may be difficult. We describe a 2‐year‐old girl presenting with pink dermal papules on the forehead, thighs, elbows, knees, and palms of the hands. Based on clinical findings and skin biopsy results, she was initially diagnosed with granuloma annulare. At 5 years of age, she developed arthritis, fatigue, and more widespread skin papules leading to the diagnosis of MRH. To our knowledge, this is the youngest individual with MRH yet described. We outline the timeline and unique features of her case and review the literature pertaining to MRH in children. Although rare, MRH can be permanently debilitating, making prompt diagnosis critical. A standardized approach to investigation and management needs to be developed.     

POST KALA-AZAR DERMAL LEISHMANIASIS

Summary.— A case of post kala-azar dermal leishmaniasis is reported to illustrate the late onset of the dermal changes and the difficulties of diagnosis.     

Neurothekeoma: report of a case in an infant and review of the literature

Neurothekeomas (nerve sheath myxomas) are uncommon benign tumors of nerve sheath origin. We describe an infant with a neurothekeoma and review the literature of neurothekeomas in children and adults. Neurothekeomas have been reported in 292 patients whose ages have ranged from 15 months to 84 years. They occur twice as often in women as in men. Neurothekeomas were most commonly located on the upper extremities and the head and neck. They also occurred on the trunk, the lower extremities, and mucosa. Histologic variants of neurothekeomas include classical, cellular, and mixed tumors. Surgical excision was the most common treatment. Recurrences were attributed to an incomplete excision; treatment of these tumors is by complete excision. Neurothekeomas should be included in the differential diagnosis of dermal nodules in infants and children.     

儿童色素减退性蕈样肉芽肿在皮肤镜及反射式共聚焦显微镜下的特征

目的 探讨临床表现为色素减退的儿童蕈样肉芽肿在皮肤镜及反射式共聚焦显微镜（RCM）下的特征,分析皮肤镜联合RCM与组织病理诊断色素减退性蕈样肉芽肿的一致性。方法 2014年11月至2015年10月皮肤科门诊收集皮肤镜及RCM下疑似色素减退性蕈样肉芽肿患者15例,获取并分析影像资料。所有患者均经组织病理、免疫组化及相关检查。结果 皮肤镜联合RCM诊断疑似色素减退性蕈样肉芽肿15例,其中13例经病理证实为色素减退性蕈样肉芽肿。色素减退性蕈样肉芽肿皮肤镜下特征表现为皮纹明显,可见白色糠秕状鳞屑;色素减退呈网格状、斑马样或波点状模式;血管呈点状、短细线状、精子样或星状模式。RCM特征为表皮各层及真表皮交界处较多高折光细胞,部分可见Pautrier微脓疡,基底层色素环折光减弱,色素环外较多高折光细胞分布。结论 色素减退性蕈样肉芽肿在皮肤镜和RCM下有特征性表现,可作为儿童色素减退性蕈样肉芽肿早期筛查及辅助诊断的方法。     

Histopathology and Immunofluorescence of Discoid Lupus Erythematosus in Children

Abstract: The histopathology and immunofluorescence of discoid lupus erythematosus (DLE) are well documented In adults, but in children they have not been studied systematically. We reviewed nine skin biopsy specimens from six children with DLE. Only three specimens showed the well-developed epidermal changes seen in lesions of adults with DLE, and in the other six, these changes were either mild or absent. All nine specimens showed some degree of vacuolar alteration of the basal layer, ranging from focal and mild to severe. They all had a moderate to heavy lymphocytic dermal infiltrate in a perivascular and periadnexal distribution. Direct immunofluorescence performed on five specimens of lesional skin was weakly positive for IgM or IgG in three cases, negative in one, and strongly positive for IgM, IgG, IgA, and C3 in one. This study indicates that the range of histologic and immunofluorescence features in children with DLE is similar to that in adults. The histologic findings are distinctive enough to be useful in establishing the diagnosis, although clinico-pathologic correlation is required.     

MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi

BACKGROUND: The histopathologic differential diagnosis of Spitz nevus (SN) from malignant melanoma (MM) may be difficult. OBJECTIVE: Our purpose was to determine the staining pattern and usefulness of MIB-1 antibody, which recognizes Ki-67 antigen in formalin-fixed, paraffin-embedded tissue, as an adjunct to the histopathologic differential diagnosis of SN. METHODS: Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic nevi (MNs) were immunostained with the MIB-1 antibody. RESULTS: The mean counts of MIB-1--stained tumor cells of the epidermal and dermal components, both alone and together, were significantly lower in SNs and MNs than in MMs (P <.0001). The dermal counts showed the best discriminating power. In addition, the mean dermal/epidermal count ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly lower than the corresponding ratio (0.94) in MMs (P <.0001). CONCLUSION: MIB-1-stained tumor cell counts, especially of the dermal component, and dermal/epidermal MIB-1 count ratios may be helpful as an adjunct to the histopathologic differential diagnosis of SN.     

Distal‐type epitheloid sarcoma mimicking a wart in a child: A diagnosis not to be missed

Epithelioid sarcoma is a rare soft‐tissue tumor that occurs mainly in children and young adults. It typically presents as a subcutaneous or deep dermal mass in distal extremities. Due to its benign‐appearing clinical presentation, infrequent occurrence, and histologic similarities with other pathologies, the diagnosis of epithelioid sarcoma in its early stages can be extremely difficult and can be easily confused with benign lesions such as warts or foreign body granuloma. In this paper, we report the case of a 12‐year‐old boy with a distal‐type epithelioid sarcoma of the hand and wish to emphasize the difficulties of diagnosing this potentially lethal tumor both clinically and histologically.     

Multiple juvenile xanthogranulomas in a 13-year-old

A 13-year-old Caucasian girl presented with a 1(1/2) month history of multiple, asymptomatic, discrete, orange-yellow to skin-colored, dome-shaped, smooth, 3 to 6 mm papules on the arms, legs, trunk, and buttock. Pathology showed a dermal infiltrate of Touton-type giant cells, scattered lymphocytes, and macrophages. The patient was diagnosed with juvenile xanthogranuloma. We present this patient because of the uncommon presentation of multiple juvenile xanthogranulomas in a 13-year-old. Although juvenile xanthogranuloma generally occurs in infancy, it must be included in the differential diagnosis for an older child. This entity can less frequently occur in adults and typically a solitary lesion is found. Multiple juvenile xanthogranuloma is rare in older children and adults. Work-up should include a thorough review of systems, physical examination, and ophthalmology examination. Pediatricians and dermatologists should be aware that juvenile xanthogranulomas might occur in older children.     

The cutaneous manifestations of sinus histiocytosis with massive lymphadenopathy

Ten patients with sinus histiocytosis with massive lymphadenopathy (SHML) also had cutaneous involvement. Seven of the ten were children. The skin lesions were solitary in three patients and multiple in seven. They were papular or nodular, up to 4 cm in diameter, and often had a xanthomatous appearance. Microscopically, they were constituted by a dermal infiltrate made up predominantly of histiocytes, plasma cells, and lymphocytes. Some of the histiocytes contained phagocytosed lymphocytes in their cytoplasm. The microscopic differential diagnosis includes dermatofibroma, xanthoma, Tangier disease, histiocytosis X, reticulohistiocytoma, juvenile xanthogranuloma, and leprosy.     

Reticular erythema with focal mid‐dermal elastophagocytosis (REMDE)

A 57‐year‐old man presented with a persistent arcuate partly reticular erythema of the upper chest. Histopathological examination revealed an upper and mid‐dermal perivascular and interstitial dermatitis with macrophages which had engulfed elastic fibers. Additionally a focal dermal elastolysis was observed. The characteristic clinicopathological constellation has hitherto been reported in only 3 cases, including our case. Presumably, the disease belongs to a spectrum of clinical manifestation of mid‐dermal elastolysis. It is suggested to gather future cases under the provisional diagnosis ‘‘reticular erythema with focal mid‐dermal elastophagocytosis” (REMDE) to gain more insights into this rare disease.     

Epidermotropic xanthoma mimicking balloon cell melanoma

Xanthomas of the skin may mimic balloon cell melanoma because 1) both lesions may exhibit a diffuse dermal proliferation of cytologically similar large vacuolated or clear cells with distinct cytoplasmic membranes, 2) dermal maturation (smaller deep dermal nuclei) is absent in both lesions, 3) melanin pigment is usually absent in balloon cell melanoma, 4) cellular atypia may be minimal in balloon cell melanoma, and 5) mitoses may be absent or rare in balloon cell melanoma. We report a unique xanthoma, which further simulated melanoma by exhibiting epidermotropism and a pseudonesting pattern at the dermal-epidermal junction. The correct diagnosis was made with an immunohistochemical panel revealing tumor cell positivity for CD68 and negativity for S-100 protein and MART-1. Immunohistochemical studies may be required in the critical differential diagnosis of epidermotropic xanthoma and amelanotic balloon cell melanoma.