Histiocytosis Histiocytosis in Childrenin Children

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Dr. Javaria RasheedDr. Javaria RasheedPostgraduate TraineePostgraduate Trainee

Paediatric Medicine Unit-IPaediatric Medicine Unit-INishtar Hospital, Multan.Nishtar Hospital, Multan.

DefinitionDefinition

Prominent proliferation or Prominent proliferation or

accumulation of cells of accumulation of cells of

monocyte-macrophage system monocyte-macrophage system

of bone marrow originof bone marrow origin..

IncidenceIncidence

1 in 200,000 children each year.1 in 200,000 children each year.

AgeAge1-15 years1-15 yearsRate peaks at 5-10 years.Rate peaks at 5-10 years.

PrevalencePrevalenceCaucasions Caucasions Affects males twice than females.Affects males twice than females.

ClassificationClassification

Class 1Class 1

Langerhan’s cell histiocytosis (histiocytosis X)Langerhan’s cell histiocytosis (histiocytosis X)

Class 2Class 2Hemophagocytic lymphohistiocytoses (HLH)Hemophagocytic lymphohistiocytoses (HLH)

• Familial Hemophagocytic lymphohistiocytoses Familial Hemophagocytic lymphohistiocytoses (FHLH)(FHLH)

• Infection associated Hemophagocytic syndrome Infection associated Hemophagocytic syndrome (IAHS)(IAHS)

Class 3Class 3• Acute monocytic leukemia Acute monocytic leukemia • True malignant histiocytosisTrue malignant histiocytosis

Langerhan’s cell Langerhan’s cell histiocytosis histiocytosis

(histiocytosis X)(histiocytosis X)

3 Groups3 Groups 1. 1. Unifocal (eosinophilic granuloma)Unifocal (eosinophilic granuloma) Slowly progressive diseaseSlowly progressive disease Expanding proliferation of langerhan cells in Expanding proliferation of langerhan cells in

various bones, skin, lungs and stomach.various bones, skin, lungs and stomach.

2. Multifocal Unisystem2. Multifocal Unisystem Characterized by fever, bone lesions and Characterized by fever, bone lesions and

diffuse eruptions usually on scalp and in the diffuse eruptions usually on scalp and in the ear canals.ear canals.

50% of cases involve pituitary stalk leading to 50% of cases involve pituitary stalk leading to diab. insipidus.diab. insipidus.

Triad of diab. Insipidus, exophthalmos and Triad of diab. Insipidus, exophthalmos and lytic bone lesions is called Hand-Schuller lytic bone lesions is called Hand-Schuller

Christian DiseaseChristian Disease..

3 Groups3 Groups

3. Multifocal Multisystem (Letterer-Siwe 3. Multifocal Multisystem (Letterer-Siwe

Disease)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%.

PathologyPathology Disease spectrum results from clonal Disease spectrum results from clonal

proliferation of proliferation of

cells resembling epidermal dendritic cells called cells 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 monocyte Clonal proliferation of cells of monocyte

lineage containing lineage containing birbeck granule birbeck granule

(Tennis Racket shaped)(Tennis Racket shaped) CDCD1a 1a positivity of lesional cells. positivity of lesional cells.

Clinical Clinical ManifestationsManifestations

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 Asymptomatic, pain, local swelling, fractures, collapse

of of vertebral body causing secondary compression of spinal vertebral body causing secondary compression of spinal cord, chronically draining infected ears.cord, chronically draining infected ears.

2. Skin – 50% 2. Skin – 50% Hard-to-treat scaly papular, seborrhic dermatitis Hard-to-treat scaly papular, seborrhic dermatitis

of scalp, diaper, axillary, post. auricular regions, of scalp, diaper, axillary, post. auricular regions, back, palms & soles.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 – bilateral 6. Exophthalmos – bilateral

7. Gingivitis7. Gingivitis

CandidiasisCandidiasis

8. Otitis media – 30-40% 8. Otitis media – 30-40%

may lead to deafness may lead to deafness

9. 9. Pulmonary infiltration – 10-15% Pulmonary infiltration – 10-15% (on radiography)(on radiography)

10. Pneumothorax – rare 10. Pneumothorax – rare 11. Pituitary dysfunction / 11. Pituitary dysfunction /

hypothalamic involvementhypothalamic involvement Growth retardation Growth retardation Diab. insipidusDiab. insipidus

12. Primary hypothyroidism12. Primary hypothyroidism13. Systemic manifestations13. Systemic manifestations

Fever, weight loss, malaise, irritability, Fever, weight loss, malaise, irritability, FTT.FTT.

14. Anemia / Thrombocytopenia14. Anemia / Thrombocytopenia

2 Uncommon But Serious 2 Uncommon But Serious Manifestations of LCH is :Manifestations of LCH is :

1. Hepatic involvement 1. Hepatic involvement Leading toLeading to cirrhosis associated cirrhosis associated with multisystem diseasewith multisystem disease

2. CNS Involvement2. CNS InvolvementAtaxia, dysarthria, seizures and Ataxia, dysarthria, seizures and other other neurological symptomsneurological symptoms. .

DiagnosisDiagnosisTissue biopsy :Tissue biopsy :Diagnostic and easy to perform on skin or bone Diagnostic and easy to perform on skin or bone

lesions.lesions.

Others :Others :CBCCBCLFT’sLFT’sCoag. studies.Coag. studies.Skeletal SurveySkeletal SurveyChest RadiographyChest RadiographyUrine OsmolalityUrine Osmolality

Treatment & PrognosisTreatment & PrognosisSingle 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 Systemic chemotherapy: Vinblastine or etoposide

are effective in treating LCH.are effective in treating LCH. Goal is to reduce reactivation of disease and long Goal is to reduce reactivation of disease and long

term consequences. term consequences.

Experimental TherapiesExperimental Therapies

For unresponsive disease often in young For unresponsive disease often in young children with children with

multisystem disease and organ dysfunction:multisystem disease and organ dysfunction:Immunosuppressive therapy :Immunosuppressive therapy : CyclosporinCyclosporin Anti-thymocyte globulinAnti-thymocyte globulinNew agents :New agents : ImatinibImatinib 2 – Chlorodeoxyadenosine2 – Chlorodeoxyadenosine

&& Stem Cell TransplantationStem Cell Transplantation