Congenital Self-healing Reticulohistiocytosis: An Underreported Entity

Langerhans cell histiocytosis (LCH), also known as histiocytosis X, is a general term that describes a group of rare disorders characterized by the proliferation of Langerhans cells.¹ Central to immune surveillance and the elimination of foreign substances from the body, Langerhans cells are derived from bone marrow progenitor cells and found in the epidermis but are capable of migrating from the skin to the lymph nodes. In LCH, these cells congregate on bone tissue, particularly in the head and neck region, causing a multitude of problems.²

The spectrum of LCH includes 4 variants: congenital self-healing reticulohistiocytosis (CSHR)(also known as Hashimoto-Pritzker disease), Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma (also known as pulmonary histiocytosis X)(Table). Despite the various clinical presentations and levels of severity, all variants are caused by the proliferation of Langerhans cells. We present a case of CSHR in a 6-month-old male infant that was initially diagnosed as molluscum contagiosum. We believe the actual incidence of CSHR may be underreported due to its spontaneous regression and low rate of clinical recognition.

Case Report

A 6-month-old male infant was referred to our clinic by his pediatrician with a generalized cutaneous eruption of 3 weeks’ duration. The eruption, which followed a recent viral upper respiratory tract infection, was characterized by multiple flesh-colored to erythematous, umbilicated papules distributed along the postauricular region, scalp (Figure 1A), abdomen (Figure 1B), and anterior aspect of the neck. Due to his recent illness, the patient was diagnosed with molluscum contagiosum by the referring pediatrician that was treated symptomatically with hydrocortisone lotion, Schamberg’s cream formulated in our office (a compound mixture of zinc oxide, menthol, calcium hydroxide solution, and olive oil), and pediatric diphenhydramine as needed. During a subsequent visit 2 weeks later, a more potent topical corticosteroid and a low-dose systemic corticosteroid was prescribed for 1 week due to development of new lesions and exacerbation of existing lesions. On follow-up 1 week later, the lesions on the trunk had improved, but the patient had developed new lesions on the scalp that differed from prior findings in that they were darker (more erythematous to brown) and firmer (papules and nodules).

Figure 1. Multiple fleshcolored to erythematous, umbilicated papules on the frontal scalp (A) and erythematous papules on the abdomen (B).

A shave biopsy was obtained from the frontal scalp to rule out LCH. Histologic examination and culture of the biopsy specimen revealed an atypical cellular infiltrate effacing the dermoepidermal junction and extensive epidermotropism. Focal erosion of the epidermis and an acute inflammatory exudate were visible. The nuclei of the cellular infiltrate were enlarged and hyperchromatic with a characteristic reniform appearance and indistinct nucleoli (Figure 2). The cells were admixed with scattered eosinophils and extravasated red blood cells.

Figure 2. Low-power view of dermal mononuclear cells with reniform nuclei (A)(H&E, original magnification ×100), and high-power view of enlarged and hyperchromatic nuclei with a characteristic reniform appearance admixed with eosinophils and extravasated red blood cells (B) (H&E, original magnification ×400).

Figure 3. Immunohistochemical staining of the biopsyspecimen was strongly positive for CD1a and S-100expression (original magnification ×400).

Immunohistochemical staining of the biopsy specimen was strongly positive for both CD1a and S-100 expression (Figure 3). Histopathologic findings were consistent with LCH. Clinicopathologic correlation strongly favored the diagnosis of CSHR.

Comment

Congenital self-healing reticulohistiocytosis is a rare, benign, congenital variant of LCH that spontaneously resolves with no systemic involvement. The more aggressive forms typically manifest at birth or during the first 2 months of life and regress within 3 to 4 months.⁵ Since CSHR was first described in 1973 by Hashimoto and Pritzker,⁵ more than 100 cases have been reported, but the true incidence is believed to be higher than reported given the high rate of spontaneous resolution and the low rate of clinical recognition.² The first reported case of CSHR occurred in a female infant who presented at birth with multiple, diffusely distributed, red-brown papules that were 2 to 4 mm in diameter. Although the patient received no treatment, the exanthem completely resolved within 3.5 months without recurrence at 14-year follow-up.⁵ Most often, CSHR presents as multiple papules or nodules with occasional disseminated crusting and is followed within a few months by a dramatic and spontaneous regression. Lesions may heal with mild postinflammatory hyperpigmentation. Pseudo-Darier sign, the propensity to urticate from physical manipulation, has been reported in some lesions with an increased number of mast cells.⁶ Extensive superficial nasal and oral mucosal erosions have been reported in 2 cases.⁷ Solitary lesions have been reported in 25% of cases.⁸