Some Skin Manifestations in Hypoparathyroidism

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SOME SKIN MANIFESTATIONS IN HYPOPARATHYROIDISM

BY LEO SPIRA, M.D. (VIENNA), MJD. (PBAGXJE), M.R.C.S. (ENG.)

A complex disease picture prevalent in this country the endocrine apparatus, that there is a close asso- has been traced (Spira, 1928) to the protracted ciation between the parathyroids and the vegetative ingestion of drinking water derived from the tap, nervous system. It is as yet impossible to state and of food prepared in aluminium cooking utensils. whether it is the sympathetic or the parasym- No indication could at that time be given of the pathetic which is primarily involved when this exact irritant, beyond stating that a mineral or association is disturbed by the action of fluorine. metal seemed to be involved. Further observation It is, however, likely that it is the disturbance of revealed a frequent association with paraesthesiae the equilibrium of the two great divisions of the affecting the hands and fingers, especially those vegetative nervous system, which brings about a supplied by the dorsal cutaneous branch of the decreased function of the parathyroid glands, with ulnar nerve. The feet were affected to a lesser subsequent disturbance of the calcium metabolism extent. Since there is, in the present state of our of the body. The solution of the all-important knowledge, only one poison which affects the ulnar problem whether it is the vegetative nervous nerve, namely, fluorine, Spira (1933) concluded that system alone which is attacked by fluorine, or it may be this halogen which was one of the whether some higher part in the central nervous aetiological factors concerned. It was the wide- system is attacked first, must be left to further spread occurrence of mottled teeth in this country research. Lachmann (1941) suggests the possibility (Spira, 1942a, 6), known to be produced by a that in the process of hypoparathyroidism a drinking water with a content of not less than 1 part calcium-regulating centre in the brain is involved. of fluorine per million parts of water (1 p.p.m.), Fluorine may be found in many media. It may equivalent to gr. 1/120 of fluorine to a pint of water, be present in the soil as a natural constituent and ingested during the period of calcification of the find its way into the water. Spira (19436) has teeth, which helped to establish the fact that it is shown that the filter powder frequently employed indeed fluorine which is the causative agent pro- in this country to purify, by means of metal filters, ducing signs and symptoms of a hitherto obscure water derived from rivers, lakes, ponds, etc., may origin. contain fluorine as an impurity, and thus affect the Mottled teeth have already been recognized by drinking water. The iron and cement tanks, and the various writers as bearing a striking resemblance to pipes conducting the water from its source to the a dental lesion produced by Brdheim (1906, 1911) tap from which it is drawn for drinking and cooking in his parathyroidectomized rats. Independently, purposes, may all contain fluorine as an impurity. however, of this important finding, Spira (1942c, d) In the production of aluminium cooking utensils appears to have been the first, so far as can be the mineral cryolite of the chemical composition ascertained, to draw attention to the frequent co- Na3AlF6 (or 3NaF.AlF3), which after purification existence of mottled teeth with dystrophies of other contains roughly 50% fluorine, is employed as an organs of ectodermal origin, namely, the skin and essential raw material. In the process of preparing its appendages, the nails and hair. As all these food the aluminium is readily corroded by both organs are regulated by the parathyroid glands, and acids and alkalies, with the result that the fluorine also because frequent attacks of paraesthesiae are compounds contained therein are set free and known to bepathognomonic of hypoparathyroidism, contaminate the food. he came to the conclusion (Spira, 1942c, d) that, in Since the appendages of the skin, namely, the the protracted action of fluorine, the parathyroids teeth, nails and hair, have been clinically found to are vitally involved. The disease picture of chronic be damaged through the protracted action of toxic fluorine poisoning (fluorosis) has thus been estab- amounts of fluorine upon the vegetative nervous lished to be identical with that produced by system, with subsequent involvement of the para- Erdheim (1906, 1911) in his experimental parathyroid glands (Spira, 1942c, d, 1943a, 1944a, b, thyroidectomy (tetania parathyreopriva). 1946), the question arose as to how the skin itself On further study of the symptomatology of reacts in the process of hypoparathyroidism. The fluorosis,. Spira (1946, 1947) found, in perfect object of the present paper is to record the results harmony with well-known facts concerning the of clinical observation on such dermatoses as relationship of the vegetative nervous system with were found frequently, though not invariably, to

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 94 Some shin manifestations in hypoparathyroidism accompany signs and symptoms of chronic fluorine manifests itself in a great variety of changes. Apart poisoning; and also to discuss certain skin diseases from the characteristic eruptions, vasomotor in- which were for a long time, even before the subject stability leads to perniosis and chilblain develop- of the deleterious action of fluorine came under ment. There is an increased susceptibility to in- closer scrutiny, believed to be due to parathyroid fections such as boils, pustules and carbuncles, insufficiency which in turn leads to a reduction of perionychia and fissures. Changes in the mucous the calcium content of the body. The ectodermal membranes of the upper respiratory tract leading to lesions concerned are in the main characterized by chronic catarrh, bronchitis and asthmatic disorders, mottling of the teeth, mottling of the nails, and by rhinorrhoea and hay fever, infected antra and other alopecia. sinuses, pyorrhoea and gingivitis, and so-called In the course of investigating great numbers of 'soft teeth', all belong to its symptomatology. apparently healthy young men and women in this Dyspepsia, flatulence and chronic constipation are country for any effects of hypoparathyroidism its outstanding features. caused by the protracted ingestion of toxic amounts Since all these signs and symptoms were shown of fluorine (Spira, 1942a, b, c, 19446), seborrhoeic to constitute the disease picture of chronic fluorine dermatitis over the typical areas in the inter- poisoning (Spira, 1942c, 1944a, 6), it appears that scapular region and over the sternum has been fluorosis and 'seborrhoeic diathesis' are identical found to be a common occurrence. It was often a conditions, and that it is the fluorine which is at matter of surprise to observe with what resigned the root of the diathesis. Any infection present is of indifference the victims looked upon their skin a secondary nature (Spira, 1944a), and is brought disease, so long as it was not causing them too much about by the tissues having become less resistant to inconvenience. The incidence was considerably an attack by endogenous or exogenous agents, when greater amongst the males than amongst the their calcium content has fallen below the normal females. A similar divergence in the degree of level. It is a well-established fact that the action of alopecia, so prevalent in this country, between the this halogen consists in precipitating calcium salts, sexes has been tentatively explained (Spira, 1946) which are stored in the body as a material indis- by the possibility that smaller quantities of fluids pensable for sustaining the vitality of most of the containing toxic amounts of fluorine may have been organic functions, and substituting sodium or ingested by females, rather than by the possibility potassium for the calcium which has been removed. that the ovarian hormones act in an antagonistic It is suggested that Barber's (1929) conception of a manner upon the function of the parathyroids. faulty metabolism as a cause of 'seborrhoeic Probably no dermatological problem has ever diathesis' can now be narrowed down to denote a been studied more extensively than seborrhoeic faulty calcium metabolism as the fons et origo of the dermatitis. Yet the knowledge of its aetiology is as condition. Thus, contrary to the time-honoured scanty as that of the great majority of other skin explanation, it may be not the seborrhoea which affections. Whilst, in this era of bacteriology and causes the dermatitis, the eczema, and such dys- parasitology, the condition is still widely held to trophies as seborrhoeic warts, seborrhoeic alopecia, be due primarily to an infection (Dowling, 1939), etc., but fluorine which, in its ultimate effect, evidence is accumulating to show that the old con- simultaneously damages some or all of the organs of ception of 'seborrhoeic diathesis' is being revived. ectodermal origin, the skin as well as its appendages, Barber (1929) emphasizes that the condition is the the teeth, nails and hair. Buschke (1911) describes result of a faulty metabolism, the effects of which are seborrhoea on the bridge of the nose, Kerley (1930) not only visible on the skin, but produce such systemic and Fleischmann (1931a, b) seborrhoea capitis, and disturbances as gingivitis, chronic nasopharyngeal Schwarz (1935) an impetiginous rash over the scalp catarrh with frequent exacerbations, marked hyper- in association with ectodermal dysplasias, and trophy of the lymphoid tissue, and flatulence. Levy-Franckel & Juster (1926) incriminate the According to him, this faulty metabolism causes an disturbance of the sympathetic and endocrine alteration in the secretion and composition of the systems in the aetiology of seborrhoea. In Roholm's cutaneous fat, thus producing an environment (1937) series of sixty-eight cryolite workers, eight which enables harmless saprophytes normally in- men (11-8 %) were affected by a rash on the upper habiting the skin to become parasites. It is note- part of the chest and back, consisting of chronic worthy that the same author (Barber, 1921a, 6) folliculitis with a varying degree of suppuration, adduces most of the features shown by him to be scars and pigmentation. characteristic of' seborrhoeic diathesis' as belonging In view of the fact that chemically fluorine also to the syndrome of alopecia areata. belongs to the group of halogens, two other members Ingram (1939) denies that micro-organisms play of which, namely, bromine and iodine, are known to any important role in producing seborrhoeic skin produce, amongst other diseases acne vulgaris, it lesions. He states that the seborrhoeic diathesis is reasonable, in the absence of these halogens, to

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 LEO SPIRA 95 assume that the frequent occurrence of this chronic of acne. There was also follicular hyperkeratosis inflammatory disorder involving the sebaceous over the chest and back. glands is, in a country in which fluorosis is endemic, It has been recently suggested (Sayer, 1942) that attributable to the protracted action of toxic the seborrhoeic dermatoses are an external mani- amounts of fluorine. Tendlau (1902), Wheelon festation of a syndrome caused by vitamin B (1925), MacQuaide (1944) and Spira (1947) found an deficiency. Pillsbury & Stemberg (1937) draw association of acne with ectodermal dystrophies, attention to the close relationship which exists and Richter & Herzfeld (1932) recorded two cases between vitamins, hormones and the vegetative of toxicodermias produced by iodine and arsenic nervous system. Spira (19446), too, quotes several respectively, which were cured by the administra- authors whose experimental work led to the con- tion of parathyroid extract. Dermatology is also clusion that vitamin D and parathyroid extract not familiar with those numerous cases of dermatitis only act in a similar manner upon the calcium affecting the beard region and designated sebor- metabolism, but are also capable of replacing each rhoeic sycosis barbae, an eruption which is often other, should the body be deprived of either of them refractory to every form of local treatment. A few for any reason. such cases, unsuccessfully treated at various skin An inspection in this country of the feet of 850 hospitals for several years by means of local men and 850 women (Spira, 19446) revealed the applications only, were permanently cured within fact that as many as 62 % of the former and 55 % 6-8 weeks, mainly by a regime directed against of the latter were afflicted with a condition known chronic poisoning by an irritant contained in the as 'dhobi-itch'. The degree of the affliction was drinking water and aluminium cooking utensils, any variable, and the disorder at one time or other additional local treatment having played only a incapacitating. Since the eruption was frequently secondary role. In his experiment on two dogs, associated with ectodermal dystrophies and other extending over a period of 587 and 626 days re- signs of chronic fluorine poisoning, Spira (1942 c, spectively, Roholm (1937) administered perorally 19446) suggested that ' dhobi-itch' is another mani- daily doses of cryolite to one of them, and sodium festation of fluorosis, and that any fungus that may fluoride to the other. Towards the close of the be found should be looked upon as a secondary experiment a scaly and itchy dermatitis developed infective agent. in both animals on the facial skin, especially around 'Dhobi-itch' was often found to be associated the mouth. with a similar eruption on the hands and fingers Gaul (1937), in studying the elemental consti- known as dysidrosis and cheiropompholyx, an tuents of psoriatic lesions, administered sodium association which has also been emphasized by fluoride in doses varying between 0-05 and 0-125 g. Dowling (1932). Like 'dhobi-itch', dysidrosis has to patients suffering from psoriasis vulgaris. He for many years been held to be due to an infection states that this resulted, after a week or .10 days, in by a fungus. Darier (1919) goes so far as to state the development of a pustular dermatitis on the that 'the dysidrosiform eruptions are mostly, and area generally affected by seborrhoea, and that the probably always, of mycotic origin and due to the eruption was indistinguishable from that following epidermophyton'. Since, however, a mycelium the ingestion of bromides and iodides. could in many cases not be detected, these derma- It is known that the increased sebum excretion is toses have been divided into at least two groups, frequently associated with hyperhydrosis. In fact, namely, epidermophytosis and occupational dysi- seborrhoeic dermatitis is by some believed to be the drosiform eruptions. Industrial medicine is, no result of an interaction of sebum and sweat. The doubt, acquainted with the fact that cheiropom- following case, however (Spira, 1947), which I pholyx occurs frequently amongst cement workers. attributed to the action of fluorine begun already in Spira (19436) examined several samples of the intra-uterine life, demonstrates the fallacy of this ingredients employed in the process of cement conception. A man, 31 years old, suffered from mixing, such as'clay', 'chalk','lime'and'cement', congenital ectodermal dysplasia with involvement before tap water has "been added to mix the con- of the skin and its appendages, the hair, teeth and crete, and found that some of them contained nails. His chief complaint was intolerance to heat fluorine. In his view, cheiropompholyx which due to inability to perspire. Even intravenous attacks susceptible cement workers is attributable injection of 7-5 mg. (0-0075 g.) of pilocarpine hydro- to their handling such ingredients as contain chloride succeeded in producing no more than fluorine as an impurity. Burckhardt (1938), in small glistening beads of sweat on his forehead and discussing the aetiology of the cement- and chalk- frontal scalp, but none on any other part of the eczema encountered in plasterers, states that skin body. Yet, over his sternum and between the tests with various cements, chalk, and ingredients shoulder blades and in the scalp follicular sebor- of cement on healthy skins may produce in rhoeic dermatitis was present, with occasional areas every person a reaction which, both clinically and

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 96 Some skin manifestations in Jiypoparathyroidism histologically, is an eczema. He holds that the cement- pompholyx was found by him frequently to be and chalk-eczema is in most cases a toxic, not an co-existent with ectodermal dystrophies and other allergic, manifestation. In view of the frequently signs and symptoms of chronic fluorine poisoning, expressed belief that dysidrosis is sometimes asso- he suggested that cheiropompholyx, too, is caused ciated, with excessive sweating, and therefore due by the protracted ingestion of toxic amounts of to a disease of the sweat apparatus, it is interesting fluorine. He reported (Spira, 1928, 1933, 1942c, d, to note that Spira's (1947) patient suffering from 19446) that several cases of cheiropompholyx, ' congenital ectodermal dysplasia of the anhydrotic including his own, which for a long time failed to type' •was found to have recurrent attacks of respond to any method of local treatment, yielded cheiropompholyx, although biopsy of the skin promptly within a few weeks to a regime based taken from one of his fingers revealed absence of chiefly on avoiding food prepared in aluminium sweat glands and the pilocarpine test failed to cooking utensils, substituting a pure and wholesome produce sweat at his finger tips. drinking -water for tap water, and eliminating the Cheiropompholyx, however, frequently affects amount of poison accumulated in the body by an also people -whose occupation does not bring them effective adsorbent (charcoal) and an aperient. into contact with any of these or other minerals Scheuermann (1938), too, obtained good results in which might act as irritants on their fingers and some cases of haematogenous toxic dysidrosis by hands. Moreover, the symmetrical distribution of means of a protracted administration of an aperient the affected parts also in this group of victims of the and charcoal. disease is an additional reason for the belief that the A disturbance of the sympathetic and endocrine eruption is of a central origin. Both the frequent systems in dysidrosis has been stressed by Levy- co-existence with each other and with the dys- Franckel & Juster (1926), and the importance of the trophies of the teeth, nails and hair, singly or in association of the vegetative nervous system with combination, and the similarity in the appearance the endocrine apparatus as a factor in the causation of the dermatoses seem to indicate that 'dhobi- of dysidrosis is also emphasized by Leszczynski itch' and cheiropompholyx are identical, and that (1929 a). In his view, the equilibrium of the vegeta- they are external manifestations of a systemic tive nervous system is disturbed in dysidrosis either disease. Dowling (1932) draws attention to the well- by the tonus of the sympathetic being increased or recognized fact that seborrhoeic eczema of the scalp by that of the parasympathetic being decreased. and other parts may be accompanied by an eruption In discussing vesicular eruptions of the hands and of the palms and soles, identical with dysidrosis. feet, Lehmann (1930) states that in dysidrosis Darier (1919) states that the victims of cheiro- internal influences are important predisposing pompholyx are almost always dyspeptic, neuras- factors. He observed a frequent association of this thenic and depressed, and Mitchell (1929) found dermatosis with hypochlorhydria, with attacks of that in dysidrosis a history of furunculosis and of indigestion and constipation, with bad teeth and severe pustular paronychia is common. Milian & pyorrhoea, with rhinitis, and with nervousness and Per in (1921) found an association of dysidrosis with marked tremor of the fingers. He holds that the malformation of the teeth, with mottled teeth, and underlying pathological changes are trophic in with the ear lobules attached to the sides of the face. nature, and governed by the sympathetic nervous Darier (1921), Sabouraud (1921), Scheuermann system. Administration of calcium lactate, and (1938) refute the suggestion, made by Milian & thyroid and parathyroid extracts proved distinctly Perin (1921), of a syphilitic origin of dysidrosis, and helpful in his case. Darier (1919), Sabouraud (1921) note a frequent Oumming (1876), quoted by Leszczynski (1929a) co-existence of intertrigo (Hebra's eczema margi- and Dowling (1932), considers cheiropompholyx to natum) with dysidrosis. be a sign of gout because the fingers are thickened Spira (1928) attributed cheiropompholyx to the in a fashion similar to that seen in arthritis, and protracted ingestion of an irritant contained in Kemeri (1929, 1930a, 6) found a frequent co- drinking water and aluminium cooking utensils. He existence of dysidrosis with rheumatism, which was recorded a case of this affection which occurred, in caused by a focal infection, such as chronic rhinitis, addition to a papular eruption on the forehead and bad teeth, tonsillitis and tonsillar abscesses. Frey & to rectal haemorrhage and albuminuria, in a new- Orzechowski (1920), who were the first to note an born child delivered by Caesarean section of a association of otosclerosis with latent tetany, men- woman suffering from eclampsia.* Since cheiro- tion peeling of the skin of the palms due to dysidrosis hi one of their cases. * It is in this connexion of great interest to note that Erdheim (1906) quotes Jeandelize (1903) for the state- changes in some of the parathyroids in cases of eclamp- ment that eclampsia gravidarum is due to a disturbance sia, and Vassale (1906) obtained good results from the in the action of the parathyroid glands. According to administration of parathyroid gland in the treatment of the same source, Pepere (1905) found degenerative this condition.

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 LEO SPIRA 97 Cheiropompholyx is sometimes aeeompanied on fact that several dermatoses were recorded to have the mucous membranes by tiny vesicles and been successfully treated by parathyroid hormone. pustules which break down to form shallow ulcers Foerster (1916) believes that no one particular and fissures. Ulcerative and aphthous stomatitis, dermatosis is characteristic of parathyroid patho- when occurring simultaneously with ectodermal logy. A careful analysis, however, of the numerous dysplasias, has been shown (Spira, 1944a) to belong reports on cases in which dystrophies of the teeth, to the symptomatology of fluorosis. Those afflicted nails and hair were accompanied by dermatoses with 'dhobi-itch' are often found also to be reveals some regularity in the appearance of certain suffering from intertrigo in the groins, axillae and skin changes. Amongst them the frequent occur- the interglutaeal region, a condition designated by rence of keratosis palmaris et plantaris is striking. the collective name of tinea, although a fungus It has been observed to accompany ectodermal cannot always be detected. It is this co-existence of dysplasias by MacKee & Andrews (1924), Tobias the lesions of the hands and feet, and on the (1925), Janitzkaja & Rjabow (1928), Clouston mucous membranes, which sometimes renders the (1929), Bloch & Stauffer (1929), Falconer (1929), differential diagnosis from foot-and-mouth disease Brain (1930), Gordon & Jamieson (1931), Fleisch- difficult. mann (19316), Bowen (1932), Dodds (1935), Lord & Attention has been drawn on previous occasions Wolfe (1938), and Young (1944). Levy-Franckel & to the frequent occurrence of furunculosis in chronic Juster (1923, 1926) accuse a disturbance of the fluorine poisoning. In surveys of 1099 men and sympathetic and endocrine systems, and Spira women with mottled teeth in this country (Spira, (1947) a disturbance of the vegetative nervou 1942c) and of 850 men and 850 women examined system and the parathyroids of producing kerato- at random (Spira, 19446) as many as 324 subjects dermias. Kraus (1903) and Jadassohn & Lewan- (29%) and 533 subjects (31 %) respectively, stated dowsky (1906) give prominence to this anomaly of that they had suffered from boils at one time or keratinization. Thus the frequent occurrence of other. It is noteworthy that of the 533 people in palmar and plantar keratosis lends further support the latter survey no fewer than 368 were men, to the similarity of some of the features in chronic and only 165 were females. It may be justifiable arsenical poisoning on the one hand and chronic also in this case to apply the same explanation of fluorine poisoning on the other, a similarity which the marked divergence in the incidence of furuncu- was emphasized by Spira on several occasions. losis between the sexes as was given in the case of The cutaneous lesions associated with ectodermal alopecia and seborrhoeic dermatitis (vide supra). dysplasias have been reported to be frequently The prompt disappearance of furunculosis of what- papular in nature. The papular eruption may ever extent and duration in an otherwise apparently appear on any part of the body, but is found most healthy subject, which is obtained by a regime often on the face. It was noted by Jadassohn & directed against fluorosis is remarkable. The follow- Lewandowsky (1906), MacKee & Andrews (1924), ing is an illustrative case: Jacobsen (1928), Janitzkaja & Rjabow (1928), Some years ago a patient of mine who was Weech (1929), Falconer (1929), Gordon & Jamieson acquainted with my views on the subject advised, (1931), Hill (1933), Dodds (1935), Stephenson without my intervention, his relative abroad who (1936), de Silva (1939) and Lowenburg & Grimes was suffering from intractable furunculosis which (1942). In the patient of Margolis & Krause (1939), had resisted every kind of treatment for a long time, who was suffering from tetany following strum- to avoid food prepared in aluminium cooking uten- ectomy, the skin presented numerous dry scaly sils, if any were used in his household, and to take areas over which there were numerous minute dry large doses of charcoal and an aperient. I was papules; with improvement of the tetany the skin, subsequently informed by my patient that his has resumed a normal appearance and texture. relative had, in fact, used aluminium in his kitchen, The skin lesions in hypoparathyroidism are, and that the regime recommended resulted in a however, not always papular in character. The case prompt cure within a few weeks. of Mendes da Costa & Van der Valk (1919) showed The co-existence of dystrophies of the teeth, nails a vesicular dystrophy of the skin, and that of and hair, singly or in combination, with patho- Clouston (1929) pustular bullae on the soles of the logical changes of the skin has been recorded by feet. Furthermore, several writers have noted a numerous observers even before ectodermal dystro- similarity between psoriasis vulgaris pustulosa and phies were recognized as forming a distinct group impetigo herpetiformis. Danbolt's (1937) patient within the disease picture of chronic fluorine was suffering from impetigo herpetiformis, but poisoning. Foerster (1916), Cooper (1930) and seven years later from psoriasis vulgaris compli- Hutton (1939) recall that inhypoparathyroidismthe cated by the plaques becoming surrounded by skin is in many cases secondarily involved, and vesicles and pustules, thus turning into a case of Richter & Herzfeld (1932) draw attention to the psoriasis pustulosa, the clinical course of which was J. Hygiene 45

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 98 Some skin manifestations in hypoparathyroidism closely similar to, if not identical with, that of the about a remission, by the administration of para- first eruption. thyroid, in a case of impetigo herpetiformis compli- Schardorn's (1921) two cases of impetigo herpeti- cating tetany which followed strumectomy. Rapp formis were associated with tetany resulting from (1931), too, records a similar case, and considers it strumectomy. He quotes the various theories con- to be a toxicodermia. Since, amongst other areas, cerning the aetiology of this eruption: Hebra who the intertriginous regions were affected, the lesion was the first to describe it in 1872, and who in- was first thought to be of mycotic origin, although criminated changes due to toxins originating in the no fungus could be detected. In Tenlen's (1937) uterus during pregnancy as the responsible factor; case of impetigo herpetiformis which recurred Dubreuilh who thought that the condition is con- during three consecutive pregnancies, Chvostek's nected with a predisposition which may remain sign, at first negative, became positive as the dormant, but becomes manifest should an occasion condition of the skin grew worse. The child born arise, such as arises most frequently during preg- on the interruption of the first pregnancy died from nancy ; du Mesnil who, not being enlightened by the convulsions two days after birth. In the mother, results of microscopical examination, assumed that the pustules disappeared, the impetigo herpeti- the dermatosis may be due to a disturbance of the formis was replaced by exfoliative dermatitis, there nervous system, since several signs and symptoms was paronychia, and the hair of the scalp, the axillae accompanying it point in this direction; Dauber who and the pubic region fell out entirely. A complete held that some kind of toxaemia is the cause; regeneration of the skin, nails and hair took place Tomassoli who, whilst rejecting the mycotic theory a few weeks later. The attack of impetigo herpeti- as a convenient refuge for many dermatological formis during the third pregnancy was cured by conditions, believed that we are dealing with a injections of parathyroid extract and calcium, in manifestation of a metabolic disturbance, and addition to a gonadotropic hormone from the attributed ' this strange and very rare dermatosis to anterior lobe of the hypophysis, and a healthy child a peculiar and mysterious form of intoxication was born at full term. Lachmann (1941) observed which is derived partly from the gastro-intestinal impetigo herpetiformis complicating 'idiopathic' tract, and partly, namely to a larger extent, from hypoparathyroidism. the entire body totius substantiae';* Scheuer who It is now known (Bruhns, 1924; Bloch, 1926) that expressed the opinion that the noxon, wherever it impetigo herpetiformis is not limited to pregnancy may come from, produces the features of eclampsiaf alone, and that it may affect non-pregnant women and as well as those of impetigo herpetiformis; and even men as well. Whilst there can be no doubt that finally Ziemann who stated that ' this is the case of each one of the mentioned theories concerning its a congenital or acquired debility of some inner- aetiology is based on very reliable and painstaking secretory organ which cannot cope with the in- observation, it seems reasonable, in view of the creased function imposed by the pregnancy. It recorded additional information available, to sug- fails, and causes signs of deficiency or signs of gest that it is the sum of these theories, now further hyperfunction of the antagonistic glands, in any extended by our recent knowledge of the action of case a disturbance of the endocrine equilibrium', fluorine, which appears fully to explain all the but ' we do not know which organs or which organ aspects of the disease. The target of attack by this is the starting point of the disturbance'.* In highly potent noxon has been thus far clinically Schardorn's (1921) view, the impetigo herpetiformis traced back to the vegetative nervous system, whose is an autointoxication caused by a deficiency in the fibres supplying the parathyroid glands seem to be parathyroid function. He quotes Breier who noted affected so as to produce hypoparathyroidism and, an attack of eclampsiaf in impetigo herpetiformis. reduction of the calcium content of the body. Walter's (1922, 1927) case of impetigo herpeti- Under normal conditions, and whilst the available formis was associated with osteomalacia. It will be calcium supply is sufficient to replace the calcium remembered that osteomalacia has been shown by depot which is being depleted through the action of Erdheim (1911) to have occurred in some of his fluorine, no serious ill-effects will ensue. If, how- parathyroidectomized rats. Leszczynski (1928) ever, the fluorine is permitted continually to enter considers impetigo herpetiformis to be an intoxica- the body, with the result that the calcium content tion dermatosis, the result of an endocrinopathy remains constantly below the normal level, and caused in particular by a dysfunction of the para- more especially, if pregnancy supervenes, during thyroids, and Brill (1928) believes that the condi- which the mother parts with some of her own, tion is intimately connected with a disturbance of already deficient, calcium content so as to share it the calcium metabolism. Lutz (1928) has brought with the foetus, the chance of impetigo herpetiformis developing in a woman who, moreover, may be particularly susceptible, is just as great as is that * Translated from the German text. of the other ectodermal signs of tetany arising, for f Vide supra, p. 96, footnote on eclampsia.

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 LEO SPIEA 99 instance brittleness of the nails, loss of hair, etc., clinically signs and symptoms of chronic fluorine which are frequent features even in normal preg- poisoning appear to be identical with those of nancy (Scherber, 1909). chronic thallium poisoning, both being traced back The similarity between impetigo herpetiformis to a mode of action through the same channels. and pustular psoriasis (a similarity to which Pruritus and acute and chronic urticaria are well- Scheuermann (1938) adds certain, forms of dysi- established signs of fiuorosis. Under the name of drosis) assumes significance by the clinical evidence 'heat-spots' or 'heat-bumps' derived, from the which indicates that both dermatoses are caused popular belief that they are caused by an 'over- by a hypofunction of the parathyroid glands. heated' blood, urticaria constitutes a frequent According to Leszczynski (1928, 19296, 1931, 1936) complaint amongst the population of this country. psoriasis vulgaris is of endocrine origin. He was the Levy-Franckel & Juster (1926) attribute urticaria first to draw attention to the fact that it is in many to a disturbance of the endocrine and sympathetic cases associated with a positive Chvostek's sign, nervous systems. Csillag (1930) reports that a case which in his series occurred nearly three times as of pruritus which persisted for 15 years showed often in patients suffering from psoriasis as in non- signs of definite improvement after charcoal was psoriatics, thus indicating that the parathyroids given for not more than 7 days. are frequently involved; and he stated that the From the larger group of urticaria a dermatosis exudative and pustular component complicating was detached under the name of lichen urticatus the picture is brought about by a superadded (papular urticaria) by Bateman as long ago as 1813, damage to the parathyroids. He reports that but its aetiology remained obscure until it was peroral administration of calcium and injections of observed that the eruption is frequently accom- parathyroid extract were, in some cases, followed panied by signs and symptoms of a systemic by a remarkable improvement of both the latent condition. Funk & Grundzach (1894) found it tetany and the co-existent impetigo herpetiformis always associated with rickets and digestive dis- as well as pustular psoriasis. The same result was turbances, and in particular with flatulence and obtained by Scherber (1938) by appropriate anti- severe constipation. Barber (1914) considers this tetanic treatment. very common disease of childhood to be a mani- This similarity is further strengthened by the fact festation of a 'scrophulous diathesis', in the same that impetigo herpetiformis may be associated with way as seborrhoeic eczema is a manifestation of severe polyarthritis in a manner characteristic of the 'seborrhoeic diathesis'. He believes that the psoriasis arthropathica. Wohlstein( 1931) describes a exudative diathesis is perhaps dependent on ab- case of impetigo herpetiformis which was compli- normalities in the ductless glands, and that the cated by severe arthritis deformans with onycho- association of papular urticaria with a pathological dystrophies and other changes, such as are en- condition of the lymphoid structures, such as countered in endocrine dysfunction. A co-existence adenoids, enlarged tonsils, etc., and also with of impetigo herpetiformis with severe arthritis gastro-intestinal disorder, is too frequent to be deformans, with onycholysis, and with alopecia has coincidental. also been reported by Buschke & Boss (1931) who The theory of an association of lichen urticatus state that the similarity of the arthritic changes in with a dysfunction of the endocrine apparatus was impetigo herpetiformis to those of psoriasis arthro- strengthened by Cornbleet (1929) who was the first pathica permits the assumption of a certain aetio- to report that subcutaneous injections of para- logical equality in the sense of an endocrine thyroid extract in conjunction with peroral admini- dysfunction which can be ascribed to both these stration of calcium laetate in massive doses were diseases. followed, even without any local treatment, by a In Vohwinkel's (1929) case of psoriasis arthro- prompt relief of the pruritus and subsequent dis- pathica, severe arthritis deformans was accom- appearance of the papular urticaria. Pillsbury & panied by considerable decalcification of the bones, Sternberg (1937), too, obtained excellent results in by total alopecia, and by deformed, brittle and their patients with lichen urticatus treated by longitudinally striated nails. The sudden and com- hypodermic injections of parathyroid extract and plete loss of hair led him to believe that all these peroral administration of calcium laetate or gluco- dystrophies may be produced in a manner closely nate, in addition to local treatment. similar to that produced by thallium, that is to say, Lichen urticatus has been found by several in- through the vegetative nervous system and the vestigators to occur mostly during the summer parathyroid glands. He recalls an observation by months, and Hallam (1927, 1932) includes the Baer (1907) of a rapid and complete cure obtained by disease in the allergic group with hay fever, asthma intravenous and intramuscular injections of calcium and infantile eczema. He draws attention to the in a case of severe psoriatic arthritis. It should be fact that change of environment has sometimes a remembered that Spira (1946), too, showed that remarkable effect on the course of both papular 7-2

Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.93, on 24 Sep 2021 at 22:32:57, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0022172400013711 100 Some shin manifestations in hypoparathyroidism urticaria and asthma. Kinnear (1933), Gordon turbance of the endocrine and vegetative nervous (1933) and Tate (1935) reported that the eruption system in those of Oliver & Gilbert (1926), Gordon cleared immediately on confining the patient to a & Jamieson (1931), Whittle (1944) and Spira (1947). hospital, or even on change of residence, whether Atrophia cutis was an outstanding feature in the any therapy was instituted or not, with a rapid cases of Jones & Atkins (1875), Tendlau (1902), recurrence of the lesions on the patient's return Kraus (1903), Christ (1913) and Strandberg (1919). home. Gordon (1933) assumed that some cases of Singer (1921) elicited Chvostek's sign in one of his lichen urticatus are dermatological neuroses. It patients who exhibited atrophy of the skin in would, however, be interesting to investigate association with ectodermal dystrophies, and found whether the pronounced seasonal incidence of the a cataract in another, thus establishing the presence disease is not due to taking, during the summer of parathyroid insufficiency in both cases. months, larger quantities of fluids which may have The patients of Tobias (1925) and Wende (1926) contained toxic amounts of fluorine, and whether with ectodermal dysplasias were affected by epi- the disappearance of the eruption following the dermolysis bullosa, and Hesse (1930) and Pinter removal of the patient to a different environment (1930) reported that their patients suffering from was not due to a supply of pure and wholesome epidermolysis bullosa exhibited onychodystrophies. drinking water in the new locality. Bray (1933) hi Drosdek's (1930) case there was an association of observed that the condition is frequently associated epidermolysis bullosa with palmar and plantar •with enuresis, migraine and asthma. The fact that hyperkeratosis. Kerl (1930) recorded a case of this these latter disorders are known to be due to dermatosis complicated by onchodystrophies (pit- sympathetic-parasympathetic imbalance may per- ting, onychorrhexis, Beau's lines, onychoatrophy); haps give further support to this new conception of administration of calcium prevented further de- the aetiology of lichen urticatus. velopment of bullae. Schwartz & Levin (1923) Eczema was observed to accompany the syndrome obtained a distinct improvement in a child suffering of ectodermal dystrophies by Montgomery (1916), from epidermolysis bullosa by giving calcium lactate Pulay (1926), Jacobsen (1928), Bowen (1932), Hill and parathyroid extract. (1933), Lord & Wolfe (1938), Friedman (1940) and Sellei (1931, 1932) obtained good results in the Tomasi (1940). Lachmann (1941) records the case of treatment of chronic alimentary urticaria, Quincke's a patient suffering from post-operative hypopara- angioneurotic oedema, dysidrosis (eczema dysi- thyroidism, who sub finem exhibited a violent droticum) and eczema intertrigo by means of eczematous skin lesion. Hutton (1939) states that hypodermic injections of parathyroid extract and infantile eczema is probably most often complicated peroral administration of calcium. He recalls that by thyroid and parathyroid insufficiency, with a con- calcium has a sedative action on the vegetative sequent disturbance ofthecalciummetabolism.Spira nervous system, and that the improvement which (1933) reported the case of children suffering from follows the calcium therapy, in addition to a infantile eczema which resisted every conceivable fungicide applied locally in those cases in which a method of external therapy for several years, but fungus can be detected, is due to the fact that the yielded promptly within 10 weeks to internal treat- nature of the soil which was fertile for the growth ment aimed at avoiding the chemical irritants con- of the fungus has thereby been changed into one on tained in the drinking water and aluminium cooking which it cannot thrive so easily. utensils, and eliminating the amount of poison Like Sellei (1931, 1932), Richter & Herzfeld accumulated in the body. This was at a time when (1932) succeeded by means of parathyroid hormone fluorine was not yet known to be one of the irritants. in effecting a cure in cases of chronic urticaria which He later (1942 c) described a case of infantile eczema had resisted every method of treatment for a long in a boy who was suffering from asthma as well, and time. They obtained good results also in some cases who exhibited both mottled teeth and onycho- of chronic eczema which was caused by a disturb- dystrophies as signs of hypoparathyroidism. ance of the vegetative nervous system, and a case Rhagadae at the corners of the mouth (perleche) of acne rosacea responded promptly to the admini- were noted by MacKee & Andrews (1924), Lesz- stration of parathyroid extract. czynski (1928), Weech (1929), Falconer (1929), Broekema (1933) and Schwarz (1935); and paro- The controversy concerning the question of nychia was a prominent* feature in the cases of whether a dermatosis is to be regarded as an Nicolle & Halipre (1895), White (1896), Murray affection of the skin per se, in the same way as a (1921), Fraser (1927), Thompson (1928), Weech disorder of any other organ is regarded, or whether (1929), Hill (1933), Hardwick (1939) and Spira it should be looked upon as an external manifesta- (1943a). tion of a pathological condition within the body, There was extensive lichen pilaris in the patient continues unabated. So far the progress towards a of Ziegler (1897), and keratosis pilaris with a dis- better understanding of the pathogenesis of skin

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(MS. received for publication 16. xi. 45.—Ed.)