Juvenile xanthogranuloma

Juvenile xanthogranuloma

Megan Mowbray and Olivia M.V. Schofield

Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports

Courtesy of Mary Glover, Great Ormond Street Hospital, London, UK

Juvenile xanthogranuloma (JXG) is a benign disorder characterized by solitary or multiple, yellow-red nodules in the skin, and, occasionally, in other organs. The lesions spontaneously regress by age 6 months to 3 years. It occurs most commonly in infancy and early childhood, but adults may be affected. Treatment is only recommended for systemic lesions if their location interferes with organ function.

Management strategy

The diagnosis of JXG is usually made clinically, but a biopsy is required for atypical clinical variants (giant, plaque-like, paired, clustered, infiltrative, lichenoid, linear, subcutaneous, and intramuscular) and if multiple lesions are present. JXG is classified as a ‘non-Langerhans cell histiocytosis’ and characterized histologically by an accumulation of foamy histiocytes lacking Birbeck granules (non-Langerhans cells) and multinucleated Touton-type giant cells. Immunohistochemical staining of JXG lesions shows expression of factor XIIIa, CD68, CD163, fascin, HLA-DR, and CD14, but not S100 or CD1a. This pattern of expression suggests that the cell of origin of JXG is the dermal dendrocyte. The histogenesis of this group of conditions is unclear but the relationship to LCH is thought to be a divergent differentiation from a common precursor CD34+ myeloid cell. Reported cases of the two conditions occurring in the same individual suggest that this divergent maturation is not irreversible.

The ‘JXG family’ can be divided into three groups:

Cutaneous: JXG, benign cephalic histiocytosis, generalized eruptive histiocytosis, adult xanthogranuloma, progressive nodular histiocytosis

Cutaneous with a major systemic component: xanthoma disseminatum

Systemic: Erdheim–Chester disease, rarely seen in children

In the most common solitary type of JXG (60–89% of all cases), there is a male to female preponderance of 1.5 : 1. The usually affected sites are the head, neck, and upper trunk. In young infants with multiple lesions the male : female ratio increases to 12 : 1. In the majority of cases no further investigation is required. The lesions will resolve spontaneously within months or years and no follow-up is necessary. As involvement of other organs can occasionally occur in the cutaneous group, a review of systems and general examination is recommended to look for involvement of other sites and to examine for café-au-lait macules (see below).

Eye involvement

The eye is the most commonly affected extracutaneous site of JXG. Uveal lesions are the most frequently reported ophthalmologic findings but lesions affecting the eyelid, orbit, conjunctiva, cornea, and optic nerve have also been described. Iris lesions may lead to hyphema and glaucoma. The incidence of eye involvement in cutaneous JXG is only 0.2–0.4%, but intraocular JXG can occur without cutaneous disease and can be locally aggressive.

Systemic JXG

Systemic JXG is classically defined as involvement of two or more visceral organs in addition to multiple cutaneous and subcutaneous lesions. However, there are many reports of extracutaneous involvement occurring both with and without cutaneous lesions. After the eye, the subcutis, CNS, lung, liver, and spleen are the commonest sites, but there are reports of every organ system in the body being affected. As the differential diagnosis is usually neoplasia, it is imperative to determine an accurate diagnosis. Lesions in extracutaneous sites, like the skin, spontaneously regress and therefore treatment is only indicated in cases of compromised organ function.

Triple association of JXG, NF-1, and JMML

It is likely that there is an association of JXG with neurofibromatosis-1 (NF-1). Children with NF-1 have a 200- to 500-fold greater risk of developing juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative disorder of childhood. The triple association of JXG, NF-1 and JMML has also been reported. Awareness of the increased risk of JMML in NF-1 and in cases with both JXG and NF-1 is important to ensure early diagnosis.

Association of JXG and hematologic malignancy in adults

In adults there have been sporadic reports of xanthogranulomas preceding or arising concurrently with hematologic malignancies.

Specific investigations

In most cases, no specific investigations are required

Ophthalmological assessment in children under the age of 2 years with multiple lesions

Full blood count and/or pediatric referral in children with JXG and café-au-lait macules, NF-1, or a family history of NF

Biopsy in cases of unusual clinical variants

Biopsy in cases with systemic manifestations to avoid unnecessary invasive diagnostic procedures

Radiological and clinicopathological features of orbital xanthogranuloma.

Miszkiel KA, Sohaib SAS, Rose GE, Cree IA, Moseley IF. Br J Ophthalmol 2000; 84: 251–8.

Of 150 cases of intraocular JXG, none was identified on routine screening of individuals with cutaneous JXG. Of those children with eye involvement, 92% are under the age of 2 years, and if they have cutaneous lesions these tend to be multiple.

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Tags: Treatment of Skin Disease Comprehensive Therapeutic Strategies

Aug 7, 2016 | Posted by admin in Dermatology | Comments Off

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