30 September 1978 SA MEDIESE TVDSKRIF 579

Acne, Hypervitaminosis A and Hypercalcaemia

A Case Report

KAREN J. HOFMAN, F. J. MILNE, CARYLL SCHMIDT

SUMMARY

The ingestion of vitamin A, which is often prescribed forthe treatment of acne, may lead to hypervitaminosis A.This syndrome has a wide spectrum of clinical features,hypercalcaemia being of special note since it has beenreported in 4 previous cases only. Hypervitaminosis A

has been described as resulting from excess ingestion ofvitamin A for prevention of sunburn and treatment ofminimal brain dysfunction. With the present glut of healthfoods, this condition should be borne in mind whenpatients present with symptoms of hypercalcaemia andliver dysfunction.

S. Afr. med. l., 54, 579 (1978).

Vitamin A is a fat-soluble vitamin stored predominantly inthe liver. Dietary sources include dairy products, eggs, liverand fish-liver oils. Its precursor is carotene, which is presentin carrots and tomatoes. The daily requirement is 5000ID, but for women in the third trimester of pregnancyand for lactating women 8000 ID/day are recommended.'The clinical picture of chronic hypervitaminosis A is varied,but it is well known to cause desquamation, hair loss,weakness, anorexia, nausea, vomiting, musculoskeletal pain,headaches and hepatomegaly. Associated hypercalcaemia,which occurred in our patient, has been noted in theliterature on only 4 previous occasions.'-'

CASE REPORTA l7-year-old male was referred with documented hyper­calcaemia for investigation. The calcium level was 3,4mmol/I, inorganic phosphate 1,55 mmol/I and uric acid0,58 mmol/l. He had been in good health until a yearpreviously when he started taking vitamin A 150000units/day for his acne. He began to feel lethargic. Threeweeks before admission he noticed recurrent epistaxis andthereafter experienced anorexia, nausea, vomiting, consti­pation, frontal headaches, dizziness, nocturia, lower backpain, and pain below his shoulder blades and in theregion of his right triceps muscle. Also, his hair began tofall out. At this stage he spontaneously stopped allmedication.

On examination he was found to be an alert and a well­built young man. His pulse rate was normal, blood

Department of Medicine, University of the Witwatersrand andJohannesburg General Hospital, Johannesburg

KAREN ]. HOFMAN, 6th-Year Medical StudentF. .T. MlLNE, F.C.P. (S.A.), M.D., Senior PhysicianCARYLL SCHMlDT, M.B. B.CH., Medical Registrar

Date received: 16 June 1978.

pressure was 110/70 mmHg and jugular venous pressurewas not raised. The heart and lungs were normal. Theskin of his lips was cracked, there was marked exfoliationof the skin of his palms and soles (Fig. I), and there werewhite lines at the proximal ends of all his nails (Fig. 2).Abdominal examination revealed a I-cm hepatomegaly anda I-cm splenomegaly.

Fig. 1. Complete exfoliation of skin on sole, with a smallamount of skin left on heel.

Investigations showed the following: normal blood count,prothrombin index 67°~, sodium 141 mmol/I, potassium3,5 mmol/I, chloride 104 mmol/I, glucose 5,94 mmol/I, urea11,45 mmol/I, creatinine 114,92 JLmol/I, calcium 3 mmol/I,inorganic phosphate 0,969 mmol/I, uric acid 0,413 mmol/I,total bilirubin 42,75 fLmol/l, and direct bilirubin 32,49

580 SA MEDICAL JOURNAL 30 September 1978

Fig. 2. White lines at proximal ends of nails.

J-tmol/1. Alkaline phosphatase was 304 mU/ml (normalrange 30 - 100 mU/ml), SGPT 24 mU/ml (normal range2 - 35 mU/ml), and SGOT 67 mU/mI (normal range 2 - 35mU/ml). The parathyroid hormone assay, 25-dihydroxy­cholecalciferol and carotene levels were normal, and thevitamin A level was 805 IU/IOO ml (normal range 60­200 IV/lOO rnl).

The first set of calcium levels was measured by theatomic flame spectrophotometer, while the second andsubsequent levels were measured by the o-cresolphthaleincomplexone method. (These methods are comparable, al·though the former usually gives slightly higher values.)

Radiographic examination of the skeleton was normal,except for a suggestion of a periosteal reaction on theproximal third of the medial side of the right humerus.The excretory urogram was normal. The ECG showed ashortened QT interval. On discharge, urea, creatinine andcalcium levels had all returned to normal, splenomegalyhad disappeared and the prothrombin index was 100%.The patient was lethargic, but otherwise asymptomatic.

- Exfoliation of his skin and hair loss continued.

DISCUSSIONThe features described are consistent with those of chronichypervitaminosis A. The syndrome has been found tooccur after 6 weeks of massive doses," but more frequently

occurs after 18 months on 50000 IU/day.' Toxic levelshave been attained by excess ingestion for treatment ofacne: prevention of sunburn,' treatment of minimal braindysfunction," and by eating meat of the polar bear, whichhas a high vitamin A content in the liver, during Arcticexpeditions.•

Two features which should be emphasized are. hyper­calcaemia and hepatic involvement. The hypercalcaemiaaccounts for lassitude, nausea, vomiting, anorexia:, head­aches, impaired renal function and a shortened QT intervalon ECG. The hypercalcaemia is independent of parathyroidhormone, and is the result of a direct effect of vitamin Aon the bone. According to 10wsey and Riggs'O there is anincrease in the extent of the bone-resorbing surface, en­larged osteocyte lacunae, and osteocytes which behave likeosteoclasts and resorb the bone. Hepatic dysfunction isshown by a low prothrombin index, hepatomegaly andraised bilirubin levels. Reports by Farre! et al." indicatethat on liver biopsy the ratio of fat cells to liver cells isincreased. Splenomegaly was attributed to portal hyper­tension."

In view of daily requirements, doses of 150000 IV/dayare excessive. Further, it is questionable whether vitamin Ais of any value in the treatment of acne," and certainly, ifit is used, very careful monitoring for vitamin A toxicityshould be instituted by the physician. There is no definitivetreatment for hypervitaminosis A, but abrupt cessation ofvitamin A ingestion is indicated, after which all featureswill regress over a period of months.

The authors wish to acknowledge the advice and helpfulcriticism of Or Sidney Kramer.

REFERENCES

1. Latham, M. C. (1975): Scope Mallual on Nutrition, p. 67. Kalamazoo,Mich.: Upjohn.

2. Fisher. G. and Skillem, P. G. (1974): 1. Amer. med. Ass., 227. 1413.3. Stimson. W. H. (1961): New Engl. J. Med., 265. 396.4. Katz, C. M. and Tzogoumis, M. (1972): Metabolism, 21, U7l.5. Wieland, R. G., Henricks, F. H., An"t, Y. et al. (1971): Lancet, 1.

698.6. Shaw, E. W. and Niccoli, J. Z. (1953): Ann. intern. Med., 39, 131.

698.7. Straughan, J. L. (1976): S. Afr. med. J., SO. 123.8. Shaywitz, B. A., Siegel, N. J. and Pearson, H. A. (1977): J. Amer.

med. Ass., 238. 1749.9. Shearman, D. J. C. (1978): Brit. med. J•• 1. 238.

10. Iowsey, I. and Riggs, B. L. (1968): J. clin. Endocr.• 28. 1833.11. Farrel, G. C., Bhathal, P. S. and Powell, L. W. (1977): Amer. I.

dig. Dis., 22. 724.12. Michaelsohn, G., Iuhlin, L. and VahlQuist, A. (1977): Arch. Derm..

113,31.