962 10 April 1965 Diabetes

Summary National Institutes of Health of America, the British Diabetic

Association, and the Lawson Tait Memorial Fund.
The family history of diabetes in the first-degree relatives of
1,307 patients at the diagnosis of clinical diabetes is compared
with a similar family history in 859 control-group subjects. REFERENCES
The results are matched for siblings and parents in different Doll, R., and Buch, J. (1950). Ann. Eugen. (Lond.), 15, 135.
age-groups, and are also compared with the known rate of Edwards, J. H. (1963). Amer. 7. Med., 34, 627.
clinical diabetes at different ages. Under 30, compared with a non- Harris, H. (1950). Ann. Eugen. (Lond.), 15, 95.
diabetic control, a diabetic at diagnosis is between 12 and 24 Johnson, G. W. C. (1961). Brit. 7. clin. Pract., 15, 15.
Nilsson, S. E. (1962). Acta med. scand., Suppl. No. 375.
times as likely to have a similarly affected sibling. The corre- Penrose, L. S. (1953). Acta genet. (Basel), 4, 257.
sponding rate for those aged 70 or over, is only one and a half Pincus, G., and White, P. (1933). Amer. 7. med. Sci., 186, 1.
Report of Working Party appointed by College of General Practitioners
times. The results suggest that only diabetes of early onset has (1962). Brit. med. 7., 1, 1497.
a strong genetic background. (1963). Ibid., 2, 655.
Simpson, N. E. (1964). Diabetes, 13, 462.
This investigation was supported (in part) by a P.H.S. research Steinberg, A. G. (1959). Ann. N.Y. Acad. Sci., 82, 197.
- and Wilder, R. M. (1952). Amer. 7. hum. Genet., 4, 113.
grant number CD-00058-01, from the Division of ChronicDiseases, Thompson, M. W., and Watson, E. M. (1952). Diabetes, 1, 268.

Prognosis in Raynaud's Phenomenon After Sympathectomy

E. N. M. JOHNSTON,* R. SUMMERLY,t M.B., CH.B., M.R.C.P., M.R.C.P.ED.;
M.B., B.CH., M.R.C.P.;
MARTIN BIRNSTINGL,4 M.S., F.R.C.S.

Brtit. med. J., 1965, 1, 962-964

Raynaud (1862, 1874) first described " local syncope of the professorial units of St. Bartholomew's and St. Thomas's
extremities," and Lewis and Pickering (1934) recognized that Hospitals between 1939 and 1960 and who agreed to attend
this phenomenon could result from hypersensitivity of the special follow-up clinics for further investigation formed the
digital arteries to cold (primary Raynaud's phenomenon) or group studied. Reappraisal of the symptoms, signs, earlier
could be secondary to connective-tissue disorders, arterio- investigations, and operative results was made.
sclerosis, local injury, long-standing vibration, or compression Supine barium swallows or oesophageal manometry (by the
of the subclavian artery at the thoracic outlet. Some patients method of Dornhorst et al., 1954) were done at follow-up on
apparently suffering from primary Raynaud's phenomenon the patients with primary Raynaud's phenomenon and when-
ultimately develop systemic scleroderma, the Raynaud's ever systemic scleroderma was suspected. Blood investigations
phenomenon preceding other features of this disease by several consisted of haematology (haemoglobin, white-cell count,
years. differential count, film, and blood-sedimentation rate), serology
Sympathectomy has been used in the treatment -of severe (Wassermann reaction, Rose-Waaler and latex fixation tests, L.E.
Raynaud's phenomenon of the hands since 1928, and although cells, antinuclear factor, and cold agglutinins), and bio-
the immediate post-operative results may be most encouraging chemistry (blood urea, serum proteins, electrophoresis, cryo-
the late results often are not. Few of the follow-up reports, globulins). Routine urinalysis (with microscopy) was carried
however, make any genuine reappraisal of the late operative out. Radiographs of the chest, hands, and thoracic inlet were
results in those patients initially thought to be suffering from taken. Macular telangiectases similar to those which may
primary Raynaud's phenomenon who subsequently developed occur on the hands, lips, buccal mucosa, and face in systemic
a connective-tissue disorder. de Takats and Fowler (1962) scleroderma were searched for in an unselected group of 200
consider that the chief reason for failure of upper thoracic dermatological out-patients (120 females, 80 males) aged 15
sympathectomy stems from operating on patients who are to 70 years who had never suffered from Raynaud's
suffering from incipient or unrecognized connective-tissue phenomenon.
disease, that the presence of such disease is a contraindication
to sympathectomy, and that the operation may precipitate Definitions
dissemination, especially in lupus erythematosus.
We report the results of a follow-up study of 75 patients Primary Raynaud's Phenomenon.-We have adhered to the
with severe Raynaud's phenomenon of the hands who had criteria suggested by Allen and Brown (1932), namely: (1) the
been treated by sympathectomy 3 to 24 years earlier. We have Raynaud's phenomenon should be bilateral and paroxysmal;
been especially interested in the subsequent fate of those (2) there should be no clinical evidence of diseases of the peri-
patients who were thought to be suffering from primary pheral arteries or other conditions known to give rise to
Raynaud's phenomenon, and we have tried to relate the surgical secondary Raynaud's phenomenon; (3) necrotic lesions, if
result in those patients to the final diagnosis. present, should be superficial and confined to the skin of the
finger-tips; and (4) symptoms should have been present for at
least two years at the time of diagnosis.
Materials and Methods Systemic Scleroderma.-This is the form of scleroderma in
Seventy-five patients who had had upper thoracic sympath- which systemic visceral manifestations may occur; it embraces
ectomy for severe Raynaud's phenomenon in the surgical the term "progressive systemic sclerosis" but excludes
disseminated morphoea.
* Consultant Dermatologist, Nottingham and Mansfield Hospital Group. Primary Raynaud's Phenomenon with Scleroderma-like
t St. Thomas's Hospital, London. Changes.--We have used this term for patients whose condition
t Consultant Surgeon, St. Bartholomew's Hospital, London.
10 April 1965 Raynaud's Phenomenon-7ohnston et al. BRASH
MEDICAL JOURNAL 963
fell midway between severe primary Raynaud's phenomenon years later both hands were sclerotic, and there were telangiectases
and systemic scleroderma and who may have incipient systemic on the face, lips, and fingers. Oesophageal studies confirmed the
scleroderma. They had severe trophic changes confined to the presence of systemic scleroderma. Despite the symptomatic
fingers, a small number of macular telangiectases on the hands improvement produced by the operation in the right hand, the
or lips, but no other skin changes or evidence of systemic rate of progress of the disease had been the same in both upper
involvement. limbs.
Control Group: Incidence of Macular Telangiectases.-One
Results to five macular telangiectases were found on the face in each
of 40 patients (20%) in the older age-groups; none were found
There were 51 females and 24 males; follow-up was from on the hands, lips, or buccal mucosa.
3 to 24 years (Table I). Sixty-one patients had had bilateral
sympathectomies and 14 unilateral.
The pre-operative diagnoses are shown in Table II. The Discussion
miscellaneous group comprised two patients suffering from The late results of upper thoracic sympathectomy in primary
systemic lupus erythematosus and one patient who had
dermatomyositis. All three had scarring atrophic lesions on Raynaud's phenomenon corresponded with previous reports
the fingers and distressingly severe Raynaud's phenomenon. (Buchanan et al., 1952; Gifford et al., 1958; Hall and
Hillestad, 1960). All our patients were improved during the
TABLE I.-Duration of Follow-up After Sympathectomy first six months after the operation, although some degree of
cold hypersensitivity persisted in spite of adequate sympathetic
Years . .3-5 6-10 11-15 16-20 21-24 denervation; return of symptoms occurred between the first
No. of patients . . 30 38 5 1 1 and second year after surgery. However, 18 (58%) patients
stated at follow-up that their symptoms were still less severe
TABLE II.-Results of Sympathectomy than before the operation (Table III). As in earlier reports,
the best results occurred in patients with digital-artery
Pre-operative Diagnosis Total No. Improved thrombosis; immediately after the operation tissue loss was
Primary Raynaud's phenomenon..
Digital-artery thrombosis .21
43 25 (58%)
15 (71%)
minimized and gangrene averted, while at follow-up 71% still
Systemic scleroderma .8 2 had an improvement in the Raynaud's phenomenon.
Miscellaneous .3 0
The most interesting results occurred in the 17 patients with
systemic scleroderma. Of the eight patients who at the time
None of the patients was cured by operation. Improvement of operation had sclerodactyly and widespread sclerosis of the
was recorded if, as a result of the operation, the attacks of upper limbs, only two were helped. In the eight patients with
Raynaud's phenomenon became less frequent and less severe, the slowly progressive variant of the disease characterized by
if healing of finger-tip necroses occurred, and if episodes of many years of severe Raynaud's phenomenon the operative
finger-tip necrosis and paronychial infection were reduced. results were similar to those in the patients with confirmed
Patients who experienced temporary relief lasting only one year primary Raynaud's phenomenon. The sympathectomy did not
were classed as operative failures. seem to influence the tempo of the disease in these patients,
The results of sympathectomy in relation to the pre-operative as illustrated in our patient whose initial symptoms were
diagnoses are shown in Table II. The percentage success in predominantly unilateral (see above).
primary Raynaud's phenomenon was 58 %, and in digital artery The difficulty of recognizing systemic scleroderma is demon-
thrombosis 71%. None of the three patients in the strated by our follow-up. Of the 43 patients initially diagnosed
miscellaneous group was helped, nor did the operation as having primary Raynaud's phenomenon, eight (19%) had
precipitate any deterioration in their condition. developed systemic scleroderma 6 to 24 years later. The
diagnostic difficulties arise, firstly, because in systemic sclero-
TABLE III.-Effect of Revision of Diagnosis on Outcome in Primary derma Raynaud's phenomenon may occur with visceral involve-
Raynaud's Phenomenon ment but without skin sclerosis (Tuffanelli and Winkelmann,
Fnal Diagnosis Total No. Improved 1961), and, secondly, because the slowly progressive variant of
Primary Raynaud's phenomenon confirmed ..
-

31
-

18 (58%) systemic scleroderma begins with Raynaud's phenomenon and

Systemic scleroderma . .
Primary Raynaud's phenomenon with sclero- 8 5 trophic changes on the fingers but may not involve the arms,
derma-like changes . . 4 2 face, or viscera for several years (in this series the time interval
was 3 to 20 years). Specialized procedures such as the measure-
ment of the sensory chronaxie of the skin (Jablonska et al.,
Of the 43 patients diagnosed initially as having primary 1958, 1959, 1962) and histological studies of the cutaneous
Raynaud's phenomenon, at follow-up 31 still appeared to be nerve networks (Pawlowski, 1963) are said to be helpful in
in this category, eight had developed systemic scleroderma, and distinguishing severe primary Raynaud's phenomenon from
four were placed in the intermediate group of primary Ray- incipient systemic scleroderma, but are not readily available.
naud's phenomenon with scleroderma-like changes. It is often stated that Raynaud's phenomenon of early onset
The effect of the revised diagnosis on the late operative associated with "hereditary cold fingers," chilblains, and a
results in primary Raynaud's phenomenon is shown in positive family history is tantamount to a diagnosis of primary
Table III. The striking feature is that the overall success Raynaud's phenomenon. This is not correct; three of our
rate (58%) in the patients with confirmed primary Raynaud's patients with apparent primary Raynaud's phenomenon who
phenomenon shows no improvement, because five of the developed systemic scleroderma gave such histories. This
patients who had developed systemic scleroderma and two in suggests that hypersensitivity to cold may predispose to
the intermediate group had also benefited by sympathectomy. systemic scleroderma, or at any rate may coexist. Another
One other patient initially diagnosed as having Raynaud's diagnostic difficulty arises, albeit uncommonly, when the
phenomenon secondary to digital-artery thrombosis had Raynaud's phenomenon of systemic scleroderma is initially ono-
developed systemic scleroderma at follow-up. Her case history sided, suggesting digital-artery occlusion.
demonstrates a feature of special interest. Finger-tip necroses, accepted in primary Raynaud's
A woman aged 50 developed severe Raynaud's phenomenon, phenomenon by Allen and Brown (1932), and Allen et al.
mainly of the right hand complicated by gangrene of the finger-tips. (1962), occurred in only one of our patients with confirmed
A right-sided upper thoracic sympathectomy was performed. Ten primary Raynaud's phenomenon. We believe that loss of tisue
964 10 April 1965 Raynaud's Phenomenon-;ohnston et al. bEDICAmJOURA
from the finger-tips, especially if associated with resorption of Summary
the terminal phalanges, points towards some other disease
process, in particular systemic scleroderma. Seventy-five patients who had had upper thoracic sympath-
Flat (macular) polygonal telangiectases on the hands are ectomy for Raynaud's phenomenon of the hands 3 to 24 years
unusual in patients with Raynaud's phenomenon. In this earlier were reviewed. The pre-operative diagnoses were
series they occurred in the patients with systemic scleroderma, primary Raynaud's phenomenon in 43, digital-artery thrombosis
and in very small numbers (one to three) in five patients with in 21, systemic scleroderma in 8, systemic lupus erythematosus
confirmed primary Raynaud's phenomenon. We believe that in 2, and dermatomyositis in 1.
in patients with Raynaud's phenomenon, macular telangiectases Eight patients apparently suffering from primary Raynaud's
may be the most valuable early clinical sign of incipient or phenomenon at the time of operation had developed systemic
overt systemic scleroderma if present on the hands, but are of scleroderma at follow-up, the Raynaud's phenomenon
less significance if found on the face alone. preceding other features of the disease by an interval of from
Brachial arteriography is not helpful in distinguishing 3 to 20 years.
severe primary Raynaud's phenomenon from early systemic The late results of sympathectomy were best in digital-artery
scleroderma. This procedure was performed pre-operatively thrombosis (71 % success) and in confirmed primary Raynaud's
on four of the patients initially diagnosed as having primary phenomenon (58 % success). The results were poor in patients
Raynaud's phenomenon who later developed systemic sclero- who had advanced systemic scleroderma at the time of opera-
derma. In two the arteriograms were normal, and in two tion and in the three patients who had other connective-tissue
digital-arterial blocks were demonstrated, but there was no disorders, but no dissemination of the condition resulted from
specific radiological change to indicate that systemic sclero- operation.
derma would ensue. Apart from this, arteriography affords a The patients with apparent primary Raynaud's phenomenon
reliable method of diagnosing digital-arterial blockage and was who ultimately developed systemic scleroderma responded to
used in the pre-operative assessment of a total of 15 of our sympathectomy; the operative result gave no indication of the
patients. true diagnosis. In such patients finger-tip necroses and
In the 727 patients' suffering from systemic scleroderma macular telangiectases on the hands should suggest incipient
reviewed by Tuffanelli and Winkelmann (1961) the oesophagus systemic scleroderma.
was by far the most commonly involved viscus (67 % of patients),
and for this reason oesophageal manometry or anti-gravity We are grateful to Dr. H. J. Wallace for suggesting this study.
(supine) barium swallows were performed at follow-up We thank the physicians and surgeons of St. Thomas's Hospital,
and Professor G. W. Taylor, St. Bartholomew's Hospital, for per-
in the patients with primary Raynaud's phenomenon. No mission to study patients under their care. This work was supported
unsuspected examples of systemic scleroderma were discovered, by a grant to one of us (E. N. M. J.) from the St. Thomas's Hospital
and in the borderline group (primary Raynaud's phenomenon Endowment Fund.
with scleroderma-like changes) these investigations did not help
to clarify the diagnosis. In those patients with apparent REFERENCES
primary Raynaud's phenomenon who developed systemic Allen, E. V., Barker, N. W., and Hines, E. A., jun. (1962). Peripheral
scleroderma the oesophageal abnormalities merely confirmed Vascular Diseases, 3rd ed., p. 137. Saunders, Philadelphia.
our clinical suspicions. Similarly, serological tests (L.E. cells, and Brown, G. E. (1932). Amer. 7. med. Sci., 183, 187.
Buchanan, J. L., Cranley, J. J., and Linton, R. R. (1952). Surgery, 31,
sheep-cell agglutination, latex fixation, and antinuclear factor) 62.
did not help to separate incipient systemic scleroderma from de Takats, G., and Fowler, E. F. (1962). 7. Amer. med. Ass., 179, 1.
Dornhorst, A. C., Harrison, K., and Pierce, J. W. (1954). Lancet, 1, 695.
apparent primary Raynaud's phenomenon in this series. These Gifford, R. W., Hines, E. A., jun., and Craig, W. McK. (1958). Circula-
investigations were abnormal in two patients who progressed tion, 17, 5.
Hall, K. V., and Hillestad, L. K. (1960). Angiology, 11, 186.
to systemic scleroderma, but not before the diagnosis was Jablonska, S., Bubnow, B., and Lukasiak, B. (1958). Brit. 7. Derm., 70,
clinically obvious. 37.
- (1959). Ibid., 71, 123.
A good response to sympathectomy in doubtful cases cannot and Szczepanski, A. (1962). Ibid., 74, 174.
be taken as confirmatory evidence of primary Raynaud's Lewis, T., and Pickering, G. W. (1934). Clin. Sci., 1, 327.
Pawlowski, A. (1963). Arch. Derm., 88, 868.
phenomenon, since improvement after surgery occurred in five Raynaud, A. G. M (1862). These de Doct. Paris, Rignaux.
of our patients with the slowly evolving variety of systemic - (1874). Arch. gen. Mid., 5, 189.
Tuffanelli, D. L., and Winkelmann, R. K. (1961). Arch. Derm., 84,
scleroderma. 359.

Roundworms in Fishes and so-called " Herring-worm Disease"

H. HARFORD WILLIAMS,* B.SC., PH.D.

Brit. med. J., 1965, 1, 964-967

Ashby et al. (1964) discussed some of the literature on eosino- Literature

philic granuloma of the gastro-intestinal tract in man. They
referred to 47 papers which describe a total of 89 cases From the literature and original observations on " Eustoma
and stated that, although " the herring parasite " may not be rotundatum," a species provisionally referred to as Pseudani-
responsible for all these cases, it may well be the causative sakis rotundata in this paper, attention should be drawn to the
agent in European territories. following, which show not only that the account by Ashby et at.
is greatly oversimplified but also that there is a dire need for
* Assistant Director, Commonwealth Bureau of Helminthology, St. more detailed work on all aspects of the biology of those round-
Albans, Herts. worms, which are said to establish themselves temporarily or