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CHRONIC IDIOPATHIC AGRANULOCYTOSIS Report of a Fatal Case Treated with Corticotrophin (ACTH) by I

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CHRONIC IDIOPATHIC AGRANULOCYTOSIS Report of a Fatal Case Treated with Corticotrophin (ACTH) by I 404 Postgrad Med J: first published as 10.1136/pgmj.32.370.404 on 1 August 1956. Downloaded from CHRONIC IDIOPATHIC AGRANULOCYTOSIS Report of a Fatal Case Treated with Corticotrophin (ACTH) By I. M. LIBRACH, M.B., B.Ch., D.P.H., D.C.H. Medical Officer-in-Charge, Ilford Isolation Hospital In I922 Schultz described the clinical picture In 1951 she was treated for septic feet. of a fatal necrotizing throat infection usually occurring in elderly females. Since then many On Examination cases of agranulocytosis (as it was named) have T. 102°. P. I24. Resp. 42. Depressed and ill. been described, the majority due to secondary Dry, furred tongue. Edentulous. Tachypnoea. marrow intoxication with chemical agents contain- No rash, glands, or ulceration. Both lung fields ing a benzene grouping. The primary or idiopathic showed multiple crepitations, especially in right variety still remains a mysterious malady, occurring mid zone. B.P. 135/85. Heart sounds normal. at all ages, especially in females, and about whose Hands soft, pale and smooth with little evidence of causation little is understood. articular thickening. Some saphenous varices Since 1934 only 30 cases or so have been present. recorded in the United There has been Kingdom. Protected by copyright. no survey of the whole subject in this country for Investigations the past io years, apart from the contribution of X-ray chest 2.10.52. Patchy consolidation right Adams and Witts in 1949, when five cases were lung field. Sputum: no predominant organism described and discussed. isolated. No acid-fast bacilli present. Treatment remains problematical. Many forms On admission: white cells I,6oo. No granulo- have been tried and are well known. They include cytes, only a few premature cells. splenectomy, irradiation, nucleotides, glutathione, Blood group ' O' Rh positive. liver extract, the various components of the B Sternal marrow film I.I10.52: no granulocytes. complex of vitamins, especially pyrodoxine, folic Only a few myelocytes. 42 per cent. lymphs. acid and cyanocobalamin, transfusion of whole Normoblasts +. blood or its constituents, especially leucocyte cream, bone marrow and leukaemic extracts. The Treatment greatest advance so far has been the use of anti- Benzyl penicillin, I,000,000 units intramuscu- biotics and in particular penicillin, which helps to larly six-hourly for 38 mega units. Chlortetra- http://pmj.bmj.com/ prevent those infections previously proving fatal. cycline, 500 mg. six-hourly for five days. Sodium Due to the paucity of suitable cases, reports of pentose nucleotide, 5 ml. twice daily for four days the effect of ACTH have been few in number, I.M. Aq. gentian violet, i per cent. to mouth. especially in regard to the idiopathic variety. Its One pint compatible and cross-matched blood. use in the following case, which was observed over Heparin, o0,000 units I.M. six-hourly for 2,800,000 three years, is therefore described. units. Pyrodoxine, o00 mg. I.V. for four days. Ascorbic acid, I,ooo Case Report mg. daily. on September 30, 2021 by guest. K.M.C., a housewife aged 53 -years, was first Progress admitted on 30.9.52 as a case of pneumonia. She Initial improvement occurred, apart from a her- had complained of pain in the right side of the petic eruption of the lip. The chest cleared by chest for two days. 8.10.52, but numerous small shallow ulcers of Shortly after the death of her son in 1943 she tonsillar fossae and palate developed. She was developed pains in the hands, knees, ankles and frail and weak. By 27.10.52 the ulceration was feet, which were ascribed to rheumatoid arthritis worse. On 3.II.52 a blood transfusion of one pint and treated as such. She had taken various pro- whole blood was given. Four days later pitting prietary brands of aspirin up to nine tablets daily oedema of left leg developed with tenderness in to relieve these pains without much success. Scarpa's triangle. By 11.11.52 both the leg and August I956 LIBRACH: Chronic Idiopathic Agranulocytosis 405 Postgrad Med J: first published as 10.1136/pgmj.32.370.404 on 1 August 1956. Downloaded from suae-wr I u*1 'w w --- V^I -- -* "'» 4 --> ^..N^N- I -- --T 7 _________ _ -4 *9 -- f _____________.2(n--^ ^ -f-^ - t ±__________________^ 3t*/2600 -" , HIo ^t . j I I Protected by copyright. NA'tR uomlt CouC oF LLNESS uu W^A \l4 Tm. mouth had improved. Progress, if any, was still the first half of 1955 and then readmitted to hos- very slow, but by IO.I2.52 she had recovered suf- pital with headache, coryza and increasing cough http://pmj.bmj.com/ ficiently well to go home. The leg was still swollen for seven days. Treated at home with sulphatriad. and an elastic stocking was ordered. T. 102. P. 124. Resp. 24. Flushed. Right nostril ulcerated. Bilateral basal crepitations. Increasing Follow-up pallor, lethargy, weakness, necrotic ulceration 1.1.53 to 6.6.53. Has felt well, apart from of the ongue and dysphagia occurred. occasional headaches and hot flushes. No ulcera- She died I7 days after admission and three tion present. B.P. I50/90. Weight ii st. 5 lb. years, 2/12 after originally seen. No post-mortem on September 30, 2021 by guest. Oral oestrogens prescribed. performed, but cause ascribed to broncho- 29.7.53. Readmitted to hospital with right-sided pneumonia despite negative X-ray findings. abdominal pain for three days. C.S.U.: pus cells and B. coli. W.C.C. 2,800. Polys 12 per cent. Investigations Discharged well on 28.8.53 after treatment with 25.10.55. Chest X-ray clear! C.S.U. normal. citrates and oxytetracycline. W.C.C. 500/cu. mm. No granulocytes. 28.II.53 to 27.2.54. Vague aches, headaches, 4.11.55. W.C.C. 6oo/cu. mm. No granulocytes. hot flushes, but looks and feels well. Weight 13 st. 25.10.55. Hb 99 per cent. R.B.C. 4,8oo,ooo/cu. Meibomian cyst of eyelid present. W.C.C. 1,400. mm. Polys io per cent. 4.11.55. Hb 75 per cent. R.B.C. 3,880,ooo/cu. 24.10.55. Defaulted from out-patients' during mm. Group ' 0 ' Rh positive. 406 POSTGRADUATE MEDICAL JOURNAL August 1956 7.11.55. Sternal marrow puncture; the marrow for many years; thus Spaet and Damshek record a Postgrad Med J: first published as 10.1136/pgmj.32.370.404 on 1 August 1956. Downloaded from is erythropoetic and shows red cell precursors. case in a woman of 63 years who survived for 25 No platelet deficiency. The predominant cell is a years. The present case as mentioned probably small lymphocyte: cells of the granulocyte series lived for 12 years. almost completely absent, a rare promelocyte and In a disease of such varying course and long eosinophil are seen. duration it is natural that attempts should be made The picture suggests an actual aplasia of granulo- to classify it on a 'chronological' basis. Thus cytic system. The lymphocytes are small and acute fulminating, chronic insidious, relapsing and mature. There is no accordance with a leukaemic cyclical varieties have been described. I myself state. (1946) postulated a critical level of leucopenia below which symptoms might occur. However, a Treatment study of recorded cases would seem to point to Penicillin : chlortetracycline. *chance rather than any specific pathological factor 8.i .55. Soluble corticotrophin, 25 mg. six- as the cause of the variations. hourly I.M. for three days before death. The course of the illness bears some resemblance to the reticuloses, especially leukemia and Hodg- Discussion kin's disease, both of which are characterized by There seems little doubt that the case described relapses and remissions. Whether some similar conforms to the clinical and pathological picture malignant cellular process is the cause is debatable. of idiopathic aplastic agranulocytosis. It would It is difficult, therefore, to prognosticate in a appear that the first symptoms (fleeting pains) given case. A month after the original admission commenced some time after 1943, which would of the present case her condition appeared as grave suggest that the duration of the illness was approxi- as the day on which she died, yet this occurred mately I2 years. The fact that aspirin was used three years later! The results of treatment, too, are after the onset of the joint pains makes this unlikely difficult to appraise. Credit for cure or remission as the causal factor. It is of interest that the is usually given to the last treatment employed. Protected by copyright. patient's illness started after a severe mental shock, Nowadays, when in doubt, cortisone or cortico- namely, the death of her son. Whether such shock trophin is widely employed after all else has failed. acts as a trigger mechanism, in predisposed adults Cortisone stimulates haemopoiesis, so that this at any rate, is conjectural. Although most cases somewhat rationalizes its use in haematology, occur in adults, the condition does occur in early although its mechanism is unknown. Cortico- infancy, e.g. two years (Bruck, I947; Moncrieff, trophin was used as a last resort in this case three 1951). However, at this early age it may well be years after the original diagnosis. The soluble as that the infection which usually acts as a precipi- distinct from the gel variety was employed because tating factor could be the cause rather than the it was considered that absorption would be quicker. result of the granulopenia, due to the immature Intermittent intramuscular dosage (25 mg. six- condition of the infantile bone marrow.
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