Indian Pediatrics 1999; 36:83-86 

Class I Histiocytosis Response to Combination of Etoposide and Prednisolone

Class I histiocytosis or Langerhans cell histiocytosis is a rare disorder characterized by osteolytic lesions, diabetes insipidus, proptosis, hepatosplenomegaly, lymphadenopathy and skin manifestations(1). The disease occurs with greatest frequency in infants and children. Treatment of Langerhans cell histiocytosis is yet to be established, various chemotherapy protocols have been tried(2,3,4). We report our observation on three patients of class I histiocytosis who were treated with etoposide and prednisolone.

Case Report

Three cases of Class I histiocytosis were studied and their relevant clinical and investigative parameters are summarized in Table I. Case I had some additional features like unilateral proptosis, extensive bony involvement and intractable seizures at presentation without any features of meningitis. None of. the cases had skin involvement, diabetes insipidus and otitis media.

Chemotherapy Was started with Etoposide in a dose of 100 mg/m2 IV for 3 days every month(5) with prednisolone 4e mg/m2 given initially for first 28 days of the first cycle in all 3 cases. After 6 cycles of chemotherapy, marked improvement in the form of regression in the size of lytic areas, disappearance of hepatosplenomegaly and lymphadenopathy and without any appearance of fresh lytic areas were observed. During a followup period of 6 months. with re- peat X-rays there was a regression in lesions with increase of extension of calcification. A positive response to therapy was seen in all three patients and there were no major toxicities.

Discussion

Langerhan's cell histiocytosis, earlier called histiocytosis X, is a rare disease. In the earlier times childhood histiocytoses have presented great difficulties for pediatricians. For over a century since Hand-Schuller Christian disease, a form of. childhood histiocytosis has been described, there has been considerable confusion surrounding these disorders.

The term Histiocytosis X was proposed by Lichtenstein in 1953 to underscore lack of understanding of these disorders. The various forms of histiocytosis are difficult to distinguish on clinical basis but they should be un- equivocally differentiated from one another as they require different treatment. approaches. Also one must bear in mind that the actual distinction between malignant and non-malignant forms has been difficult in the past. The new classification (Table II) not only clearly divides the various childhood histiocytosis syndromes(6) but also has a

 

TABLE 1- Clinical and Investigative Parameters of Patients

Clinical	Case 1	Case 2	Case 3
Age and Sex	31/2 yr. male	15 mo. female	4 yr. male
Duration 2 yer	2 mo	2 mo
Lytic areas scalp	+	+	+
Lymphadenopathy	+	+	+
Splenomegaly	+	+	+
Hepatomegaly	-	+	+
Anemia +	+	+
Proptosis Unilateral +	-	-
Investigations
Hemoglobin (g/dl)	8.5	7.0	9.0
Total leukocyte count (per cu mm)	12,000	8,600	9,200
Platelet count (per cu mm)	2,40,000	1,65,000	1,24,000
X-ray skull	Multiple Osteolytic Areas	Two lytic lesions in frontal area	Three lytic lesions in frontal and Parietal areas
X-ray long bones	Multiple osteolytic areas in femur, humerus	Normal	Normal
X-ray chest	Rt. Sided non-homogenous opacities	Normal	Normal
FNAC from	Class I	Class I	Class I
(a) Scalp swelling	Histiocytosis	histocytosis	histiocytosis
(b) Cervical LN	-do-	-do-	-do-
Bone marrow aspiration	Normal	Normal	Normal
USG abdonmen	Splenomegaly	Hepatosplenomegaly	Hepatosplenomegaly
Cranial CT scan	Multiple lytic areas skull vault	lytic areas skull	lytic areas skull
Urine specific gravity	1020	1022	1020
LFT	Normal	Normal	Normal
Mx test/BCG test	-	-	-
Urine VMA/HVA	Not significant	Not significant	Not significant
EEG	Normal	Not done	Not done

pathological basis because the ultimate diagnosis of all childhood histiocytosis rests on findings of pathological examination.

In the new system of classification Langerhan cell histiocytosis (Class I Histiocytosis) replaces the term Histiocytosis X as well as syndromes of Eosinophilic granu- loma. Hand-Schuller-Christian disease and Letterer Siwe disease. Class II histiocytosis represents the largest group of disorders and include the non-malignant histiocytosis in which accumulating mononuclear cell is of phagocytic cell type. Class III comprises the malignant disorders of mononuclear phagocytes. These three malignancies of mononuclear phagocytes represent a spectrum in terms of their degree of dissemination, can be conceptually related to different stages of maturation and differentiation in mononuclear phagocytic series. These represent a systemic malignant disease involving entire reticulo endothelial system(7,8).

TABLE 11- Classification of Histiocytosis Syndromes in Children

Class	Syndrome
I	Langerhans cell histiocytosis
II	Histiocytosis of mononuclear phagocytes other than Langerhans cells     . Hemophagocytic lympho histiocytosis (Familial and       Reactive)     . Sinus histiocytosis with massive Iympahdenopathy       (Rosai-Dorfm-an Disease)     . Juvenile xanthogranuloma     . Reticulo histiocytoma
III	Malignant histocytic disorders     . Acute monocytic leukemia     . Malignant histiocytosis     . True histiocytic lymphoma

Our patients had classical ma,nifestations lof Langerhan's cell histiocytosis in the form of multiple osteolytic lesions, hepatosplenomegaly: generalized lympahdenopathy and suggestive histopathological features as demonstrated by FNAC from bony swellings and lymph nodes. Lymph node biopsy was not obtained as histopathological diagnosis was made by FNAC. The etiology remains uncertain and could be related to undefined immu- nological disturbances(1). Other conditions like secondary deposits from neuroblastoma can simulate the disease, but there were no adbominal masses neither cIinicalIy nor USG wise and urine VMA and HV A levels were normal. Rarely this disorder can also be con- fused with craniofacial tuberculosis(9) but this was cIeaIly differentiated on the basis of histopathological morphology, negative tuberculin and BCG tests.

The various treatment modalities used are chemotherapy, surgery and radiotherapy for localized disease. The various chemothera- peutic agents used are Vinblastine, Etoposide, Methortrexate, Vincristine, Cyclophosphamide, 6 mercaptopurine, 2 deoxycoformycin(2,3,5) etc. Initially, Vinblastine with or without steroids was the most common regimen when systemic chemotherapy . was used for the first episode(4). But considering the side effects like polyneuropathy, bone marrow suppression and SIADH other agents were also evaluated for treatment of class I histiocytosis. As in our cases, etoposide has been successfully used to treat multisystem Langerhans celI histiocytosis without any major toxicities(2,5).

 References