Two cases of reticuloendotheliosis-Letterer-Siwe syndrome.

Diseases characterized by proliferative changes in the reticulo-endothelial system, other than the leukaemias and specific infections such as tuberculosis and typhoid fever, give rise to three main syndromes in children, but there are many atypical and intermediate forms. Originally described as three separate conditions, these syndromes, namely Letterer-Siwe disease, Hand-Schiiller-Christian syndrome, and 'eosinophilic granuloma' of bone are now believed by many authorities to have a common aetiology, as yet unknown, and basic pathology. Van Creveld (1951) is of the opinion that a distinction between the first two is unnecessary and at times impossible, and clinical pictures occupying intermediate positions between them and even sharing features of the infectious reticuloses have been described; Siwe (1949) on the other hand, maintained that they were pathologically distinct. Those authors who accept the theory of unity of Letterer-Siwe disease and Hand-Schililer-Christian syndrome do so on the assumption that lipoid storage would develop in the former if the disease were protracted; moreover, sequences of the three morbid pictures in one patient on consecutive biopsies have also been described by Bartels (1947), Wentholt and Hadders (1949), Love and Fashena (1948), and Parkinson (1949). That this sequence of events is not always followed has been shown elsewhere and is further demonstrated by the protracted course of one of the cases to be described, but in it account must be taken of the modifying effects of steroids. Considerable evidence is accumulating on the value of ACTH and cortisone in the treatment of the three syndromes, particularly of the subacute and chronic forms of the Hand-Schuller-Christian syndrome. Karlen (1952) reported disappearance of hepatosplenomegaly and exophthalmos in an 18-month-old girl on cortisone therapy, but relapse occurred when the treatment was stopped on account of severe oedema, and the patient died. R0jel and Lund (1958) described a boy with Hand-SchullerChristian syndrome aged 14 months at onset, but not diagnosed till 3 years and 9 months, who was pronounced cured after three years' treatment with ACTH and cortisone, but he was observed for only three months after cessation of treatment, and had received x-ray therapy also. Sewell (1954) presented a girl of 3 years 10 months to the Royal Society of Medicine who had shown histological features of eosinophilic granuloma of bone and later of Hand-Schuller-Christian syndrome with clinical improvement on cortisone after failure to respond to Xrays; and Flosi, Assis, Coelho Neto, Bloise, Ulhoa Cintra and Barros (1959) described a complete remission after four years almost continuous treatment with cortisone and ACTH in a boy diagnosed as suffering from Hand-Schuller-Christian syndrome when 1 year old, the symptoms having commenced about four months previously. After a year's treatment with cortisone followed by ACTH, maximum dosage 75 mg. daily, he developed marked features associated with Cushing's syndrome at which stage treatment was gradually reduced; but bone lesions which were already resolving continued to improve and eventually disappeared after four years' treatment. Bearing this evidence in mind, it is necessary to remember the occurrence of spontaneous remission which is the usual outcome in patients with eosinophilic granuloma of bone and is also well recognized in the Hand-Schtiller-Christian syndrome. Moreau (1930) found nine cases of spontaneous recovery amongst 34 cases of Hand-SchililerChristian syndrome described in the literature, and while Letterer Siwe disease is generally fatal, spontaneous recovery is possible (Lightwood and Tizard, 1954). Recovery from this disease induced by cortisone was described by Cox (1955), and Orrild and Lunding (1953) reported a case of Letterer Siwe disease apparently cured by ACTH. The object of this communication is to place