ABSTRACT
The term “histiocytoses” encompasses a spectrum of uncommon disorders characterized by proliferation and accumulation of cells of the mononuclear phagocyte system (i.e., monocytes, macrophages, or dendritic cells) in one or more tissues and organs.1 , 2 In general, they are classified into three main categories, viz. Langerhans cell histiocytoses (LCHs) (classic and self-healing subtypes), non-LCHs (NLCHs) (including several subtypes; see Table 11.1 for details), and malignant histiocytoses, with the first two groups being of greater interest for the dermatologist as skin and visible mucous membranes are often involved.1–3 Apart from malignant histiocytoses, all such conditions are classically considered reactive proliferative processes, albeit recent advances in molecular and genomic technologies have supported the possibility that classic LCH could actually be a neoplastic disease, although not necessarily a malignancy.1 , 2 <target id="page_165" target-type="page">165</target>Clinical characteristics of LCH and NLCH cell histiocytoses.
Type of histiocytosis
Cutaneous manifestations
Possible extra-cutaneous involvement
Clinical course
Langerhans cell histocytoses (LCH)
Classic LCH
Small, discrete or confluent, translucent, rose-yellowish papules possibly displaying scaling, crusting, or ulceration and most commonly involving the scalp and trunk
Bones, hematopoietic system, lymph node, pituitary gland, lungs, liver, and spleen
Single-system LCH is usually associated with a good prognosis, whereas multisystem LCH may be fatal
Self-healing LCH
Multiple or solitary elevated, firm, red-brown nodules, flesh-red lesions (angiomas-like), or reddish-brown crusted papules
Usually none
Lesions ulcerate or form brown crusts before regressing spontaneously in weeks to months
Non-Langerhans cell histocytoses
Juvenile and adult-onset xanthogranuloma
Discrete, orange-red, or red-brown papules and/or nodules progressively turning yellowish, mainly located on the upper part of the body
Very rare (eye [most common], lungs, bones, kidneys, pericardium, colon, ovaries, and testes)
Both cutaneous and visceral lesions disappear spontaneously (usually within 3–6 years)
Papular xanthoma
Diffuse and discrete yellowish papules
Usually none
Self-healing in months to years
Generalized eruptive histiocytosis
Diffuse, firm, round/oval, pink/dark red papules (symmetric in adults and irregularly scattered in children)
Usually none
Self-healing in months to years
Benign cephalic histiocytosis
Slightly raised, round or oval, orange-red or red-brown papules, mainly localized on the face
Usually none
Self-healing in months to years
Xanthoma disseminatum
Confluent red-brown papules/nodules quickly becoming yellow, mainly involving flexures, face, trunk, and proximal extremities
Pituitary gland, respiratory and ocular mucous membranes
Self-healing or persistent—possible association with multiple myeloma and monoclonal gammopathies
Erdheim–Chester disease
Similar to xanthoma disseminatum
Bones (especially lower limbs), lungs, liver, kidney, heart, and central nervous system (CNS)
Progressive course with a poor prognosis (organs failure)
Multicentric reticulohistiocytosis
Periungual “coral beads”-like red-brownish papules as well as reddish/yellowish-brownish papules (possibly coalescing into plaques) and nodules, potentially involving every area (including mucosae)
Diffuse severe polyarthritis (especially hands, knees, and wrists) and visceral involvement (occasional)—possible association with malignancies
Skin/mucosae: unpredictable course (possible spontaneous remissions)
Joints: progressive destructive course for 6–8 years and then stabilization
Solitary cutaneous reticulohistiocytosis
Single, rapidly growing, yellow-brown or red-brown nodule, often located on the head
Usually none
May involute spontaneously
Diffuse cutaneous reticulohistiocytosis
Scattered, yellow-brown or red-brown papules or nodules
Usually none
May involute spontaneously
166Progressive nodular histiocytosis
Diffuse (with flexural sparing) yellowish-orangish papules and deep nodules (from 1 to 5 cm) with overlying telangiectasia, mainly located on the trunk
Papules may also involve oral, laryngeal, and conjunctival mucosae
Progressive with no sign of spontaneous involution (but patients remain in good health)
Necrobiotic xanthogranuloma
Red-orange, violaceous, or yellow papulonodules enlarging into plaques, possibly showing central ulcerations or atrophy with teleatelangiectasias and most commonly involving periorbital areas
Oral mucosa and hepatosplenomegaly—possible association with multiple myeloma
Progressive course and prognosis depending on the underlying multiple myeloma
Rosai–Dorfman disease
Yellowish macules and patches, reddish-brown papules, and plaques and nodules that may become eroded or ulcerated
Lymphadenopathy (cervical and less commonly other districts) and extra-nodal involvement (rarer) (especially eye, bone, CNS, and salivary glands)
Often benign course with spontaneous regression in months to years
