Confusion between the two diseases has resulted from the fact that the majority of infants in the Temperate Zone have some degree of rickets. Thus the two diseases have been found very frequently associated in pathologic examination of the bones, leading some to infer that they are in some way interdependent. They have been also confused clinically, as mentioned in another connection, owing to the fact that beading of the ribs—the rhachitic rosary—has been mistakenly regarded as a pathognomonic sign of rickets, whereas it is also a sign common to scurvy. It is important to bear in mind that from the pathologic viewpoint scurvy and rickets present strikingly dissimilar pictures—the former is characterized by an almost complete cessation of activity of bone-forming elements, whereas the latter is distinguished by a hyperplastic condition leading to a marked overgrowth of cartilage and of abnormal bone. Viewed from the pathologic, etiologic and clinical standpoint, we believe that there is no basis for assuming an interrelationship between the two disorders, and that scurvy will develop as readily and as rapidly where rickets is absent as where it is present.[59]
It is premature to discuss the relationship of these two disorders from the vitamine standpoint. In 1910 Schaumann suggested that rickets was due to a lack of a specific food factor, and somewhat later Funk included it among the “avitaminosen.” Recently Mellanby, as the result of experiments on dogs, has affirmed that the fault lies in a lack of the fat-soluble or a closely-related vitamine. Investigations of the near future will probably decide the merits of this contention; our experience is that rickets develops in infants even where the diet contains adequate fat-soluble vitamine. If rickets is proved to be a disorder depending on a vitamine, it belongs, naturally, in the same group as scurvy. This would indicate relationship, but not interrelationship. Just as the mere fact that a lack of vitamines leads to scurvy and to beriberi does not signify, in theory or in practice, the existence of pathogenetic interrelationship. However, as stated, this is a subject which does not as yet rest on a secure foundation.
Osteogenesis imperfecta and osteomalacia are disorders of dietetic or metabolic origin characterized by fragility of the bones. The latter has developed new significance and importance due to its increased occurrence in almost epidemic form in the Central Empires at the close of the World War. The etiology of both disorders is most obscure. In the future in considering their pathogenesis it will be well to draw a sharp distinction between them. Osteogenesis imperfecta is a disease in which an injury occurs to the fœtus without any manifest illness in the mother, which seems to indicate a primary lesion of the fœtus (perhaps metabolic); osteomalacia, on the other hand, attacks the mother who gives birth to an apparently healthy fœtus. The latter gains added interest because it is a disease of the bones which is attributed to dysfunction of the endocrine glands, to a disturbance especially of the parathyroid. If this observation is confirmed, it furnishes another anatomical basis for associating the glands of internal secretion with pathologic conditions of the bones.
One cannot survey the various diseases of the bones—scurvy, rickets, osteoporosis, osteogenesis imperfecta, osteomalacia, etc.,—without realizing that this group is at present in a state of great confusion and will have to be rearranged and winnowed. The differentiation between some of these diseases is not in every instance clear morphologically—for instance, early cases of scurvy and osteoporosis—so that it is difficult to consider them satisfactorily from the standpoint of pathogenesis. Clinical differentiation is still more difficult and uncertain. It seems probable that new entities will be established, as has happened in the past. It is not so long since rickets included almost all the bone diseases of infants. Gradually congenital syphilis, scurvy, and achondroplasia were segregated as distinct diseases. Probably a similar separation of other pathologic conditions, now so entangled as to be indistinguishable, will be evolved.
Among the diseases which have been attributed to a vitamine deficiency are “war or hunger edema,” sprue, the “mehlnaerschaden” of infants, and the “exudative diathesis” described by Czerny and Keller. Future investigation will disclose whether any of these disorders belong in the group with scurvy. The hunger edema, noted in the late war and in previous wars, seems to be a complex condition, quite dissociated from scurvy, as many of the sufferers consumed comparatively large quantities of potatoes or other vegetables. The “mehlnaerschaden” resembles scurvy and the other vitamine disorders in its tendency to produce hydremia and susceptibility to infection. It also develops in spite of a liberal supply of antiscorbutic foodstuff in the dietary. As its name implies, it comes about on a diet containing large quantities of carbohydrate, of the cereal paps so commonly fed to infants. It is conceivable that an unbalanced diet of this kind may not provide a sufficiency of all the vitamines.
It does not seem probable that exudative diathesis, a term which implies a predisposition to develop exudations or denudations of the skin and mucous membranes, is the result of a lack of vitamine. This condition does, however, predispose to scurvy. The association was very evident in the group of cases reported by Hess and Fish in 1914. It is not without significance that the blood-vessels in exudative diathesis also show a decided weakness, an increased permeability, as judged by the “capillary resistance test.” In both scurvy and in exudative diathesis eczema and petechial hemorrhages are encountered.
There may be nutritional diseases due to an excess of food rather than to a deficiency. A superfluity may be harmful by hindering the proper utilization of the food, or may possibly lead to the formation of deleterious products. Disturbances of this kind do occur. For example, it is by no means uncommon for an infant which has been overfed with milk to show the typical signs of rickets. Young guinea-pigs which are fed liberal amounts of cow’s milk develop a disease characterized by fragility of the bones. The experience of Lubarsch, who produced osteogenesis imperfecta in rabbits by means of a diet consisting mainly of liver, or adrenal gland, is of interest, especially as this condition did not come about when they were fed muscle tissue.
From what has been stated, it must be evident that this subject not only is in a state of flux but that it is in a state of great confusion. This applies not only to the relationship of vitamines to these disorders, but to their identification and demarcation pathologically as well as clinically. During the past few years we have begun to regard these diseases from a new viewpoint, which no doubt will be helpful, but it is probable that they will not be sharply defined and their relationships determined until it is possible to bring about each disease definitely and regularly in an experimental animal. Until this time we should proceed slowly, and not bring about “confusion worse confounded” by yielding to the vogue, and grouping together heterogeneous and little-understood clinical conditions under the caption of deficiency diseases. There is a growing danger of attributing every unexplained nutritional disorder to the new, overworked, but ill-defined vitamines—of their sharing with the secretions of the endocrine glands the fate of becoming the dumping-ground for every unidentified disorder.