Histiocytosis in children is characterized by the proliferation of monocyte-macrophage cells, with an incidence of 1 in 200,000 and commonly affecting males aged 1-15 years. The condition is classified into three main types: Langerhan’s cell histiocytosis, hemophagocytic lymphohistiocytoses, and malignant histiocytosis, with a range of clinical manifestations including skeletal, skin, and systemic symptoms. Treatment varies by disease type, with benign cases often requiring local interventions and malignant cases needing systemic chemotherapy or experimental therapies.

2. Histiocytosis inHistiocytosis in
ChildrenChildren
ByBy
Dr. Javaria RasheedDr. Javaria Rasheed
Postgraduate TraineePostgraduate Trainee
Paediatric Medicine Unit-IPaediatric Medicine Unit-I
Nishtar Hospital, Multan.Nishtar Hospital, Multan.

3. DefinitionDefinition
Prominent proliferation or accumulationProminent proliferation or accumulation
of cells of monocyte-macrophageof cells of monocyte-macrophage
system of bone marrow originsystem of bone marrow origin..

4. IncidenceIncidence
1 in 200,000 children each year.1 in 200,000 children each year.
AgeAge
1-15 years1-15 years
Rate peaks at 5-10 years.Rate peaks at 5-10 years.
PrevalencePrevalence
CaucasionsCaucasions
Affects males twice than females.Affects males twice than females.

5. ClassificationClassification

6. Class 1Class 1
Langerhan’s cell histiocytosis (histiocytosis X)Langerhan’s cell histiocytosis (histiocytosis X)
Class 2Class 2
Hemophagocytic lymphohistiocytoses (HLH)Hemophagocytic lymphohistiocytoses (HLH)
• Familial Hemophagocytic lymphohistiocytoses (FHLH)Familial Hemophagocytic lymphohistiocytoses (FHLH)
• Infection associated Hemophagocytic syndrome (IAHS)Infection associated Hemophagocytic syndrome (IAHS)
Class 3Class 3
• Acute monocytic leukemiaAcute monocytic leukemia
• True malignant histiocytosisTrue malignant histiocytosis

7. Langerhan’s cell histiocytosisLangerhan’s cell histiocytosis
(histiocytosis X)(histiocytosis X)

8. 3 Groups3 Groups
1.1. Unifocal (eosinophilic granuloma)Unifocal (eosinophilic granuloma)
 Slowly progressive diseaseSlowly progressive disease
 Expanding proliferation of langerhan cells in variousExpanding proliferation of langerhan cells in various
bones, skin, lungs and stomach.bones, skin, lungs and stomach.
2. Multifocal Unisystem2. Multifocal Unisystem
 Characterized by fever, bone lesions and diffuse eruptionsCharacterized by fever, bone lesions and diffuse eruptions
usually on scalp and in the ear canals.usually on scalp and in the ear canals.
 50% of cases involve pituitary stalk leading to diab.50% of cases involve pituitary stalk leading to diab.
insipidus.insipidus.
Triad of diab. Insipidus, exophthalmos and lytic boneTriad of diab. Insipidus, exophthalmos and lytic bone
lesions is called Hand-Schuller Christian Diseaselesions is called Hand-Schuller Christian Disease..

9. 3 Groups3 Groups
3. Multifocal Multisystem (Letterer-Siwe Disease)3. Multifocal Multisystem (Letterer-Siwe Disease)
 Rapidly progressive disease.Rapidly progressive disease.
 Children below 2 years.Children below 2 years.
 Prognosis – poor.Prognosis – poor.
 5 years survival rate is only 50%.5 years survival rate is only 50%.

10. PathologyPathology
Disease spectrum results from clonal proliferation ofDisease spectrum results from clonal proliferation of
cells resembling epidermal dendritic cells calledcells resembling epidermal dendritic cells called
langerhan’s cells.langerhan’s cells.
langerhan’s cell.langerhan’s cell.
Antigen presenting cell of skin.Antigen presenting cell of skin.
Hallmark of LCH.Hallmark of LCH.
Clonal proliferation of cells of monocyteClonal proliferation of cells of monocyte
lineage containinglineage containing birbeck granulebirbeck granule
(Tennis Racket shaped)(Tennis Racket shaped)
 CDCD1a1a positivity of lesional cells.positivity of lesional cells.

17. Clinical ManifestationsClinical Manifestations

18. 1.1. Skeleton – 80%Skeleton – 80%
 Skull (most common)Skull (most common)
 PelvisPelvis
 FemurFemur
 VertebraeVertebrae
 MaxillaMaxilla
 MandibleMandible
 MastoidMastoid
Clinically :Clinically :
Asymptomatic, pain, local swelling, fractures, collapse ofAsymptomatic, pain, local swelling, fractures, collapse of
vertebral body causing secondary compression of spinalvertebral body causing secondary compression of spinal
cord, chronically draining infected ears.cord, chronically draining infected ears.

24. 2. Skin – 50%2. Skin – 50%
 Hard-to-treat scaly papular, seborrhic dermatitis of scalp, diaper,Hard-to-treat scaly papular, seborrhic dermatitis of scalp, diaper,
axillary, post. auricular regions, back, palms & soles.axillary, post. auricular regions, back, palms & soles.
 Petechiae / hemorrhages.Petechiae / hemorrhages.
3. Lymphadenopathy – 33%3. Lymphadenopathy – 33%
4. Hepatosplenomegaly – 20%4. Hepatosplenomegaly – 20%
Abdominal painAbdominal pain
5. Jaundice, Ascites.5. Jaundice, Ascites.
6. Exophthalmos – bilateral6. Exophthalmos – bilateral
7. Gingivitis7. Gingivitis
CandidiasisCandidiasis
8. Otitis media – 30-40%8. Otitis media – 30-40%
may lead to deafnessmay lead to deafness

34. 9.9. Pulmonary infiltration – 10-15%Pulmonary infiltration – 10-15%
(on radiography)(on radiography)
10. Pneumothorax – rare10. Pneumothorax – rare
11. Pituitary dysfunction / hypothalamic11. Pituitary dysfunction / hypothalamic
involvementinvolvement
Growth retardationGrowth retardation
Diab. insipidusDiab. insipidus
12. Primary hypothyroidism12. Primary hypothyroidism
13. Systemic manifestations13. Systemic manifestations
Fever, weight loss, malaise, irritability, FTT.Fever, weight loss, malaise, irritability, FTT.
14. Anemia / Thrombocytopenia14. Anemia / Thrombocytopenia

35. 2 Uncommon But Serious2 Uncommon But Serious
Manifestations of LCH is :Manifestations of LCH is :
1. Hepatic involvement1. Hepatic involvement
Leading toLeading to cirrhosis associatedcirrhosis associated
with multisystem diseasewith multisystem disease
2. CNS Involvement2. CNS Involvement
Ataxia, dysarthria, seizures and otherAtaxia, dysarthria, seizures and other
neurological symptomsneurological symptoms..

36. DiagnosisDiagnosis
Tissue biopsy :Tissue biopsy :
Diagnostic and easy to perform on skin or bone lesions.Diagnostic and easy to perform on skin or bone lesions.

37. Others :Others :
CBCCBC
LFT’sLFT’s
Coag. studies.Coag. studies.
Skeletal SurveySkeletal Survey
Chest RadiographyChest Radiography
Urine OsmolalityUrine Osmolality

38. Treatment & PrognosisTreatment & Prognosis
Single system disease (benign) :Single system disease (benign) :
 Curettage or low dose local radiation therapy.Curettage or low dose local radiation therapy.
 High chance of spontaneous remission.High chance of spontaneous remission.
 Goal is to arrest the progression of diseaseGoal is to arrest the progression of disease
Multisystem disease (Malignant) :Multisystem disease (Malignant) :
 Systemic chemotherapy: Vinblastine or etoposide are effective inSystemic chemotherapy: Vinblastine or etoposide are effective in
treating LCH.treating LCH.
 Goal is to reduce reactivation of disease and long termGoal is to reduce reactivation of disease and long term
consequences.consequences.

39. Experimental TherapiesExperimental Therapies
For unresponsive disease often in young children withFor unresponsive disease often in young children with
multisystem disease and organ dysfunction:multisystem disease and organ dysfunction:
Immunosuppressive therapy :Immunosuppressive therapy :
 CyclosporinCyclosporin
 Anti-thymocyte globulinAnti-thymocyte globulin
New agents :New agents :
 ImatinibImatinib
 2 – Chlorodeoxyadenosine2 – Chlorodeoxyadenosine
&&
Stem Cell TransplantationStem Cell Transplantation