Langerhans cell histiocytosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]Syed Hassan A. Kazmi BSc, MD [3]


Langerhans cell histiocytosis must be differentiated from other diseases that cause bone pain, cutaneous lesions, hepatosplenomegaly, and palpable lymph nodes, such as cat-scratch disease, mastocytosis, sinus histiocytosis with massive lymphadenopathy.[1][2]

Differentiating Langerhans cell histiocytosis from other Diseases

Disease Rash Characteristics Signs and Symptoms Associated Conditions Images
Cutaneous T cell lymphoma/Mycosis fungoides[3]

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Pityriasis rosea[4]
  • Pink or salmon in color, which may be scaly; referred to as "herald patch"
  • Oval shape
  • Long axis oriented along the cleavage lines
  • Distributed on the trunk and proximal extremities
  • Squamous marginal collarette and a “fir-tree” or “Christmas tree” distribution on posterior trunk
  • Secondary to viral infections
  • Resolves spontaneously after 6-8 weeks

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Pityriasis lichenoides chronica
  • Recurrent lesions are usually less evenly scattered than in cases of psoriasis
  • Brownish red or orange-brown in color
  • Lesions are capped by a single detachable, opaque, mica-like scale
  • Often leave hypopigmented macules

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Nummular dermatitis[7]
  • Lesions commonly relapse after occasional remission or may persist for long periods
  • Pruritus

courtesy of dermatology atlas

Secondary syphilis[8]
  • Round, coppery, red colored lesions on palms and soles
  • Papules with collarette of scales

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Bowen’s disease[9]
  • Erythematous, small, scaly plaque, which enlarges erratically over time
  • Scale is usually yellow or white and it is easily detachable without any bleeding
  • Well-defined margins

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Exanthematous pustulosis[11]

Hypertrophic lichen planus[13]

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Sneddon–Wilkinson disease[15]
  • Flaccid pustules that are often generalized and have a tendency to involve the flexural areas
  • Annular configuration


Small plaque parapsoriasis[19]
  • Erythematous plaques with fine scaly surface
  • May present with elongated, finger-like patches
  • Symmetrical distribution on the flanks
  • Known as digitate dermatosis
  • Lesions may be asymptomatic
  • May be mildly pruritic
  • May fade or disappear after sun exposure during the summer season, but typically recur during the winter



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Langerhans cell histiocytosis[22]
  • Scaling and crusting of scalp


Tinea manuum/pedum/capitis[26]
  • Scaling, flaking, and sometimes blistering of the affected areas
  • Hair loss with a black dot on scalp in case of tinea capitis


Seborrheic dermatitis

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Langerhans cell histiocytosis must be differentiated from other diseases that cause bone pain, edema, and erythema.

Disease Findings
Soft tissue infection
(Commonly cellulitis)
History of skin warmness, swelling and erythema. Bone probing is the definite way to differentiate them.[29][30]
(Avascular necrosis of bone)
Previous history of trauma, radiation, use of steroids or biphosphonates are suggestive to differentiate osteonecrosis from ostemyelitis.[31][32]
MRI is diagnostic.[33][34]
Charcot joint Patients with Charcot joint commonly develop skin ulcerations that can in turn lead to secondary osteomyelitis.
Contrast-enhanced MRI may be diagnostically useful if it shows a sinus tract, replacement of soft tissue fat, a fluid collection, or extensive marrow abnormalities. Bone biopsy is the definitive diagnostic modality.[35]
Bone tumors May present with local pain and radiographic changes consistent with osteomyelitis.
Tumors most likely to mimic osteomyelitis are osteoid osteomas and chondroblastomas that produce small, round, radiolucent lesions on radiographs.[36]
Gout Gout presents with joint pain and swelling. Joint aspiration and crystals in synovial fluid is diagnostic for gout.[37]
SAPHO syndrome
(Synovitis, acne, pustulosis, hyperostosis, and osteitis)
SAPHO syndrome consists of a wide spectrum of neutrophilic dermatosis associated with aseptic osteoarticular lesions.
It can mimic osteomyelitis in patients who lack the characteristic findings of pustulosis and synovitis.
The diagnosis is established via clinical manifestations; bone culture is sterile in the setting of osteitis.
Sarcoidosis It involves most frequently the pulmonary parenchyma and mediastinal lymph nodes, but any organ system can be affected.
Bone involvement is often bilateral and bones commonly affected include the middle and distal phalanges (producing “sausage finger”), wrist, skull, vertebral column, and long bones.
Langerhans' cell histiocytosis The disease usually manifests in the skeleton and solitary bone lesions are encountered twice as often as multiple bone lesions.
The tumours can develop in any bone, but most commonly originate in the skull and jaw, followed by vertebral bodies, ribs, pelvis, and long bones.[38]

Differential diagnosis

Langerhans cell histiocytosis must be differentiated from other cavitary lung lesions.

Causes of

lung cavities

Differentiating Features Differentiating radiological findings Diagnosis


  • CXR and CT demonstrates cavities in the upper lobe of the lung
  • Sputum smear positive for acid-fast bacilli and nucleic acid amplification tests (NAAT) is used on sputum or any sterile fluid for rapid diagnosis and is positive for mycobacteria.
  • Any age group
  • Acute, fulminant life threating complication of prior infection
  • >100.4 °F fever, with hemodynamic instability
  • Worsening pneumonia-like symptoms
  • CBC is positive for causative organism
  • Children and elderly are at risk
  • Empyema appears lenticular in shape and has a thin wall with smooth luminal margins
  • Pulmonary nodules with cavities and infiltrates are a frequent manifestation on CXR
  • Elderly females of 40-50 age group
  • Manifestation of rheumatoid arthritis
  • Presents with other systemic symptoms including symmetric arthritis of the small joints of the hands and feet with morning stiffness are common manifestations
  • Pulmonary nodules with cavitation are located in the upper lobe (Caplan syndrome) on X-ray
  • On CXR bilateral adenopathy and coarse reticular opacities are seen
  • CT of the chest demonstrates extensive hilar and mediastinal adenopathy
  • Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.[45]
  • Common appearance on CT is patchy consolidation,often accompanied by ground-glass opacities and nodules.[49]
  • Exclusively afflicts smokers, with a peak age of onset of between 20 and 40 years
  • Clinical presentation varies, but symptoms generally include months of dry cough, fever, night sweats, and weight loss
  • Skin is involved in 80% of the cases, scaly erythematous rash is typical
  • Thin-walled cystic cavities are the usual radiographic manifestation, observed in over 50% of patients by either CXR or CT scans.[51]
  • Biopsy of the lung


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