Congenital Self-healing Reticulohistiocytosis: An Underreported Entity

The etiology of CSHR remains unknown, though neoplastic, viral, and immunologic origins have been suggested. There have been reports that human herpesvirus 6 may contribute to the development of LCH.⁹ It may be postulated that our patient’s presentation of CSHR was potentiated by his recent upper respiratory tract illness. In the literature, CSHR is distributed equally among males and females. Prevalence is higher in the white population than in other racial groups.⁵

Although CSHR is a benign cutaneous variant of LCH, there have been reports of patients with disseminated and extracutaneous involvement. In 1 rare case, CSHR reportedly involved the eyes, producing multiple, bilateral, well-circumscribed, diffuse, yellow-white lesions of the retinal pigment epithelium throughout the posterior pole of the eyes.¹⁰ The retinal lesions spontaneously regressed along with the skin manifestations. Additionally, it was reported that a neonate in Thailand presented with CSHR at birth and 1 month later developed multiple lung cysts that had completely regressed 11 months later.¹¹ One study reported that initial diagnoses of LCH in 18 patients with only cutaneous involvement eventually progressed to systemic LCH, requiring further management.¹² When LCH is suspected, a thorough physical examination, including hematologic and coagulation evaluation, liver function tests, musculoskeletal examination, and consultation with specialists if necessary, is recommended.¹³

There are 3 additional variants of LCH. Letterer-Siwe disease is an acute form of LCH that accounts for 10% of all LCH cases and typically presents in children younger than 2 years. It involves multiple organs, including the bones, lungs, liver, and lymph nodes.¹⁴ Affected patients usually present with fever; hepatosplenomegaly; anemia; lymphadenopathy; extensive lytic skull lesions; and a generalized cutaneous eruption, appearing as a maculopapular scaling rash with underlying purpura on the scalp, neck, axilla, and trunk.³ Letterer-Siwe disease is inherited in an autosomal-recessive pattern. Diagnosis is confirmed by skin biopsy demonstrating a thinning of the epidermis and a collection of reticulum cells in the dermis.³ Letterer-Siwe disease is treated with radiation and chemotherapy; if left untreated, the disease is fatal.⁴

Hand-Schüller-Christian disease, a chronic form of LCH, is most commonly seen in children aged 2 to 6 years and accounts for 15% to 20% of all LCH cases. This LCH variant presents with a classic triad of diabetes insipidus (resulting from erosion into the sella turcica), lytic bone lesions, and exophthalmos.¹⁵ Hand-Schüller-Christian disease also affects the oral cavity, producing nodular ulcerations of the hard palate, trouble swallowing, and halitosis.⁴ The involvement of lytic bone lesions of the mastoid process and petrous portions of the temporal bones may cause recurrent or chronic otitis media and otitis externa. Hand-Schüller-Christian disease is treated with a combination of chemotherapy, radiation, and surgical excision. The mortality rate is 30%.⁴

Eosinophilic granuloma is the most prevalent variant of LCH, accounting for 60% to 80% of all cases. Characterized by Langerhans cell granulomatous infiltration of the lungs and painful cystic bone lesions, eosinophilic granuloma primarily presents in the third or fourth decades of life.¹⁶ Some studies suggest an epidemiologic association with tobacco use.¹⁷ In the preliminary stages of this disease, Langerhans cells, eosinophils, lymphocytes, and fibroblasts infiltrate and form nodules on the terminal bronchioles in the upper and middle lung zones, damaging the airway walls.¹⁸ Fibrotic scarring progresses, ultimately resulting in alveolar destruction.¹⁰ The common signs and symptoms of eosinophilic granuloma are a nonproductive cough, dyspnea, weight loss, spontaneous pneumothorax, fever, peripheral edema, and a tricuspid regurgitation murmur.¹⁴ The prognosis of eosinophilic granuloma is variable. Although some patients progress to end-stage fibrotic lung disease requiring lung transplant, there have been reports of complete remission following cessation of cigarette smoking.¹⁷

Langerhans cells travel from the bone marrow to the epidermis where they express the CD1a protein on the surface of the antigen-presenting cell. Elevated levels of cytokines, such as tumor necrosis factor α, IFN-γ, granulocyte-macrophage colony-stimulating factor, and interleukins have been seen in patients with LCH.¹ Their role in the pathogenesis of this disease remains unknown, but the elevated levels of cytokines may indicate the lack of an efficient immune system.

Histologically, hematoxylin and eosin–stained sections demonstrate an infiltrate of histiocytes, neutrophils, eosinophils, and an increased number of mast cells involving the papillary and reticular dermis. Infiltrating Langerhans cells have concave reniform nuclei¹⁸ and stain positive for CD1a, S-100, and CD68 antigens.¹⁵ In 10% to 30% of CSHR cases, Birbeck granules can be seen on electron microscopy and tend to transform into laminated dense bodies, signifying the degenerative changes seen in CSHR.¹⁵ The various forms of LCH exhibit no significant differences in the expression of the epithelial cadherin, the phosphorylated histone H3, and the Ki-67 proteins, indicating that they are simply different forms of the same disease represented on a spectrum.¹⁵