A 2-year-old girl, pancytopenia, exophthalmos, polydipsia and polyuria

Prepared by...................Pimlak Charoenkwan, M.D.
CC : Fever and paleness 1 month prior to admission.

PI : 1 month prior to admission, the patient's mother noticed that the patient looked pale. She was seen at a private hospital and was suspected of having Thalassemia disease. She was given red blood cell transfusion once. After the blood transfusion, the symptom improved temporarily and the patient later required 2 subsequent transfusion.

During the 1 month period, she had intermittent fever and rash developing at the scalp. The mother noticed that the patient drank a lot of fluid and voided more frequently than usual.
3 days prior to admission, she was seen at a provincial hospital because of hemorrhagic spots on the face, ears and body. The right eye was swelling. Physical examination at the hospital revealed paleness and enlarged liver. CBC showed a hemoglobin level of 3.4 g%, WBC 3,800/mm3 and platelet count of 34,000/mm3. The patient was transferred to Chiang Mai University hospital.
PH: previously healthy, vaccinated according to the schedule, normal development
Significant PE

BP 96/58 mmHg , PR 120/min , RR 32/min , T 37'C ,
Wt 12 kg, Ht 85 cm (H/A less than 3rd percentile)
GA : a girl with normal consciousness , afebrile
HEENT : mildly pale conjunctiva , no icteric sclera , puffy eyelids bilaterally ,Rt exophthalmos
LYMPH NODES: multiple cervical lymph node 1-2 cms, movable,firm consistency
LUNGS : equal breath sounds , no adventitious sounds
HEART : regular , no murmur
ABDOMEN : distented , normal bowel sounds , liver 4 cm below right costal margin, no splenomegaly
GENITALIA : redness and swelling of labia majora
SKIN : generalized scaling and crusting of scalp, areas of hemorrhagic erythematous maculopapular patch at frontal region, postauricular area, back , palmar surface of both hands and legs (Figure 1-3)
EXT : pitting edema 1+

Figure 1-3. show scaling and crusting of scalp (seborrheic-like lesion), areas of hemorrhagic erythematous maculopapular patch at postauricular area, and palmar surface of both hands.
Positive findings :

1. Prolonged fever, pancytopenia, hepatomegaly, lymphadenopathy, exophthalmos
2. Generalized hemorrhagic seborrheic-like skin lesions
3. Polydipsia, polyuria
4. Delayed growth
Clinical diagnosis: Pancytopenia, cause?; R/O bone marrow infiltrative conditions or bone marrow dysfunction
DDx :
1. Bone marrow infiltrative conditions

a. Leukemia: AML
b. Solid tumors: neuroblastoma, lymphoma
c. Langerhans Cell Histiocytosis
d. Other uncommon infiltrative conditions: storage diseases
2. Bone marrow dysfunction: Aplastic anemia

Investigations:
CBC : Hb 8.6 g% , Hct 27.6 % , WBC 3,100/mm3 ( N 29% , L 63% , M 6% ] , Platelet count 28,000/mm3
PBS : Normochromic, normocytic, no blast cells
PT 12.2sec(12.8) , PTT 36.4sec (35.5)
U/A : pH 8, specific gravity1.003, no RBC, 0-1 WBC , alb - , sugar -
BUN 8 , Cr 0.4 , Na 136 mmol/L, K 2.9 mmol/L, Cl 111 mmol/L, total CO2 13 mmol/L
uric acid 4 , Ca 7.6 , P 3.4 , Mg 1.53
LFT: albumin 4.3 g/dL, globulin 2.3 g/dL, alkaline phosphatase 51 U/L, AST 13 U/L, ALT 10 U/L, TB 1.65 mg/dL, DB 0.62 mg/dL
BMA : normal cellularity , decreased megakaryocytes, normal myeloid, erythroid series , M:E ratio 2:1, increased histiocytes with some hemophagocytic activity, no malignancy cells, no parasite or fungus
Imp :BM involvement with LCH
Bone survery: multiple osteolytic lesions at skull and humerus
MRI : Multiple masses in the skull and absence of posterior bright spot (pituitary)
Skin biopsy:
consistent with Langerhans Cell Histiocytosis
Diagnosis: Langerhans Cell Histiocytosis
Treatment:
1. Chemotherapy for LCH protocol

a. Prednisolone
b. Vinblastine
c. Cyclophosphamide
d. Methotrexate
2. DI:

urine specific gravity 1.003, intake 2912 ml/day output 3320 ml/day
(Urine output 11.5 ml/kg/h), urine osmolarity 80, serum osmolarity 295
Treatment: DDAVP 0.3 mcg IV (0.025 mcg/kg/day)
Figure 4-6. Bone lesions and MRI of the brain: Multiple osteolytic lesions are noted on skull and long bone films. Absence of posterior bright spot is also demonstrated on MRI of the brain.
Histiocytosis Syndromes of Childhood
The childhood histiocytoses constitute a diverse group of disorders resulting from a proliferation/accumulation of cells of the monocyte-macrophage system of bone marrow origin. Three classes of childhood histiocytosis are recognized, based on histopathologic findings.
The most well-known childhood histiocytosis, previously known as histiocytosis X, constitutes class I and includes the clinical entities of eosinophilic granuloma, Hand-Schuller-Christian disease, and Letterer-Siwe disease. The name Langerhans cell histiocytosis (LCH) has been applied to the class I histiocytosis. The hallmark of LCH is the presence of a clonal proliferation of cells of the monocyte lineage containing the characteristic electron microscopic findings of a Birbeck granule, a tennis racket-shaped bilamellar granule in cytoplasm of lesional cells.
Figure 7: (from reference #2) Birbeck granules from electron microsopic study.

Organ of involvements
Bony skeleton: 80-100%
-skull, long bones: punch out osteolytic lesions
-Mastoid bone lysis
-Hypertrophic gingivitis and loose teeth
Skin: 35-40%
-seborrheic dermatitis-like
Lymph nodes: <10%
Bone marrow: 18%
-Pancytopenia
Endocrine system
-Diabetes Inspidus
Liver
-Infiltration, portal lymphadenopathy
Spleen
Lungs
-diffuse interstitial infiltration, cysts, bullae
GI tract: unusual
-malabsorption
Treatment
1. Surgery
2. Corticosteriods: intralesional or systemic
3. Chemotherapy: consisting mainly if vinblastine and prednisolone
Suggested reading:
1. Ladisch S. Histiocytosis Syndrome of Childhood. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia: WB Saunders, 2000:1570-2
2. Arico , Egeler RM. Clinical aspects of Langerhans cell histiocytosis. Hematology/Oncology Clinics of North America. 1998:12;247-58.
Diagnosis : Langerhans Cell Histiocytosis

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