Overall, 80 % of LCH cases involve the bone [10]. In children, the skull is most commonly affected, followed by the spine, extremities, pelvis, and ribs [10]. In adults, the jaw is most often affected [10]. When the bone is solely involved, the clinical course is often benign, and spontaneous resolution may occur [10].

Dermatologic involvement is present in about half of cases, frequently in infants [10]. Clinical description is variable and includes erythema, papules, nodules, petechiae, vesicles, crusted plaques, and seborrhea-like eruptions [10]. Systemic evaluation is mandatory with cutaneous involvement because MS LCH disease is the norm, and death may occur [10].

Pulmonary involvement is usually MS LCH in children, but SS LCH in adults [10]. It is important to note that adult pulmonary LCH has been associated with smoking and may regress with smoking cessation [10]. However, adult pulmonary LCH has also been reported to have a mortality of up to 25 % [10].

When diffuse bone marrow involvement is present, life-threatening anemia and thrombocytopenia may result [10].

Twenty-five percent of all LCH and 50 % of multisystem LCH may have dysfunction or infiltration of the pituitary gland or hypothalamus [10]. Diabetes insipidus (DI) may occur at any time of the disease course and is more frequently associated with craniofacial bone lesions, ear, eye, and/or oral lesions [10]. Therefore, these systems are referred to as “CNS risk lesions” [10]. Appropriate chemotherapy may prevent DI, but rarely cures it. Approximately 50 % of patients with DI develop other pituitary hormone abnormalities [10]. Other central nervous system (CNS) lesions include bilateral symmetric cerebellar and basal ganglia lesions that result in progressive ataxia, tremor, dysarthria, dysphasia, hyperreflexia, and permanent disability [10]. This may occur in approximately half of patients with DI and/or other CNS risk lesions [10].

Solitary orbital lesions are by far the most common ocular manifestation and carry a favorable prognosis [1]. A soft tissue mass with an associated osteolytic bony lesion with sclerotic margin is often seen. The frontal bone is most commonly affected, followed by the lateral and medial orbital walls [2]. The mean age of onset is 4 years, with a range of 18 months to 30 years [2]. Presenting signs and symptoms include ptosis, proptosis, periorbital erythema, edema, amblyopia, or diplopia/strabismus [1]. Lesions involving the eyelid, conjunctiva, caruncle, choroid, orbital apex, optic chiasm, and cavernous sinus have been described [1]. Orbital LCH represents less than 1 % of all orbital tumors and inflammatory lesions [8]. Although LCH of the orbit is most commonly isolated (single system), it may be part of multisystem (MS) disease, so full systemic workup is imperative.

The implications of orbital lesions, however, are a topic of debate. In previous multicenter trials by the Histiocyte Society, patients with diabetes insipidus were twice as likely to have orbital lesions, leading the authors to conclude that the orbital involvement is a risk factor for DI [12, 13]. However, all of the cases developing DI had multisystem LCH along with their orbital lesions, and none had unifocal LCH of the orbit. Harris rebutted the conclusion that orbital involvement was a risk factor for DI, stating that he was not aware of any reported case of unifocal orbital LCH that later developed DI or CNS disease [4]. A recent multivariate meta-analysis by the Histiocyte Society appears to support Harris’ concept by showing that only auditory system and multisystem diseases are significant risk factors for DI and CNS disease, particularly the pituitary-hypothalamic region [14, 15].

Because LCH may be part of a multisystem disorder, a complete history and physical examination is necessary. Localized imaging by CT or MRI is required, as well as full body imaging such as skull x-ray, complete bone survey/bone scan/PET scan, chest x-ray, and abdomen/pelvis imaging. Systemic workup includes complete blood cell count with differential, erythrocyte sedimentation rate, electrolytes, coagulation profile, liver function testing, urinalysis with osmolarity, water deprivation test, and bone marrow biopsy [1].