Postgrad Med J: first published as 10.1136/pgmj.33.377.121 on 1 March 1957. Downloaded from I1I NEUROLOGICAL COMPLICATIONS IN HYPERSENSITIVITY By S. FAZLULLAH, M.B.(Osmania), D.T.M. & H. Late Medical Registrar, Barrow-in-Furness Group of Hospitals, Lancs.; Medical Registrar, Pontefract and Castleford Group of Hospitals, Yorks. Hypersensitivity state is the altered activity of from acute and self-limited collagen disease in cells to any foreign substances, a normal physio- that the course is protracted over many years, logical phenomenon of protective adaptation. and if they are diseases of hypersensitivity we Allergy and hypersensitivity are our saviour for must postulate that the antigenic substance must which we should be grateful to nature. Allergy be present in the body throughout this long period is now being applied commonly to the pathological of activity, probably not being neutralized due to variants of the physiological process. Allergy, defective process of the immunity. The same physiologically, allows the organism to react to can be applied to disseminated sclerosis in which antigenic substances to neutralize them. myelin sheath is involved instead of connective Antigen antibody reaction, in certain people, tissue. may end naturally without any after-effects and in others may terminate in pathological process, Hypersensitivity and Collagen Diseases presumably due to inherent individual consti- Pirquet's original concept (I903) of allergy has copyright. tutional defect and defective enzyme system in withstood the test for 50 years and is substantially certain tissues or defect in the natural process of true today. The clinical manifestations of hyper- the immunity with the production of abnormal sensitivity now can be classified in four main antibodies, possessing affinity to certain tissues groups: with a capability of injuring them. Identification i. Asthma, hay fever and infantile eczema. of antibodies, other than those occurring in 2. Serum sickness, drug allergy and contact streptococcal infection, has not been often estab- dermatitis. lished, though some have reported antireticulin, 3. Bacterial and viral allergy (yet in infancy). antimyocardial and antirenal antibodies.* At the 4. Autoimmunization, lupus, thrombocytopenia, http://pmj.bmj.com/ moment we know little about cell-fixed antibodies. haemolytic anaemia and hyperfunction of reticulo- endothelial system. with auto-antibodies formation Autosensitization (Bywaters, I956). In certain- people, autoimmunization, following There is widespread assumption that collagen autosensitivity to certain endogenous products, diseases are probably due to hypersensitivity might play a part in the production of multiple (Rich, 1946). Fibrinoid necrosis of collagen, such antibodies. A good clinical example of auto- as seen in acute rheumatism, polyarteritis following on October 2, 2021 by guest. Protected immunization is found probably in lupus erythe- infection and serum sickness (Rich, 1946), can matosus, which is presented with haemolytic also be found in mechanical injury to collagen anaemia in association with circulating antibodie§ such as in malignant hypertension, peptic ulcer proved by positive Coombs' test, thrombocyto- and acute pancreatitis (Klemperer, 1948). There penic purpura, false positive W.R., increase is no convincing evidence that collagen itself is gamma-globulin and multiple antibodies formation involved. Klemperer himself now believes that following blood transfusion. If lupus is regarded fibrinoid of lupus is probably derived from the as a disease of autoimmunization, we do not know breakdown of nucleic acid, supposed to be set in what antigenic substance is involved nor how process by gamma-globulin, a serum factor pro- it is rendered autoantigenic. Lupus, rheumatoid duced during autoimmunization. Gamma-globulin arthritis, polyarteritis and dermatomyositis differ inactivate the desoxyribonuclease inhibitor enzyme and allow nuclear of *Globulin fraction on antikidney serum tagged with degeneration leucocytes Il3 is localized primarily in the glomeruli as determined which consequently is ingested by polymorphs. by radioautograph. These deep purple staining bodies are found in Postgrad Med J: first published as 10.1136/pgmj.33.377.121 on 1 March 1957. Downloaded from I22 POSTGRADUATE MEDICAL JOURNAL March 1957 connective tissues identified by Klemperer (1948) Involvement of the central nervous system has as desoxyribonucleic acid. The same was found also been observed in Behcet syndrome (Behcet, in lupus erythematosus cell and marrow by Har- I937, I939, I940) and in Steven Johnson syndrome graves et al. (I948). (Ashby and Lazar, 195I) resembling disseminated The efficiency of cortisone and ACTH in sclerosis, presenting the same basic pathology as arresting the disease process in rheumatoid seen in hypersensitivity. arthritis and lupus may depend upon the ability There is a growing evidence to believe that of these hormonal agents to reverse this destruc- post-infectious perivenous demyelinating encepha- tive enzymatic process in the affected cells lomyelitis and post-infective polyradiculoneuritis rather than upon the unknown cause of the (Landry-Guillain-Barre syndrome) are allergic disease. This hypothesis is supported by the reactions. These diseases are manifested 7-14 prompt effect of the therapy and equally prompt days following the infection, at a time when anti- recurrence of illness upon withdrawal of these bodies are being formed with a tendency to agents. spontaneous recovery. Miller (1956) believes that Hydralazine (apresoline), used for hypertension, these are secondary to the initial vascular insult, can also produce mesenchymal reaction simulating probably due to hypersensitivity. This toxic- lupus and rheumatoid arthritic features in asso- allergic complication had been for many years ciation with lupus erythematosus cell phenomenon. the explanation of rheumatic fever and glomerulo- These lupus erythematosus cells are also found in nephritis following streptococcal infection. In penicillin sensitivity and virus hepatitis. Apreso- post-infectious neurological disorders there is a line has a strong affinity to combine with carbonyl damage to the melin sheath, while in the collagen and sulph-hydryl groups. Thus we can produce disorders connective tissue is injured. We do not the disease at will in animals and can study its know the exact mechanism of these syndromes of pathology. unknown cause. Many clinical and pathological features are common to all collagen diseases, with some varia- Clinical Material tion in intensity and distribution. Hypersensitivity The present paper deals with the neurological is a common factor to all. Disease may start disorders observed in cases with hypersensitivity copyright. with one syndrome predominating; as it pro- manifestations: drug allergy, polyarteritis, sys- gresses, this is replaced by another. In each case temic lupus, hypersensitivity angiitis and post- cellular infiltration and fibrinoid necrosis is asso- infection allergy. Twenty-one cases have been ciated with lymphoid hyperplasia and gamma- observed; signs and symptoms are analysed. globulinaemia. Increase gamma-globulin is re- garded as a response to antigen antibody reaction TABLE I No. of Diseases cases (Aegerter and Long, I949; Long, 1954, 1955). Polyarteritis .. .. .. .. .. 3 The pathology of early stage is unknown. In an vasculitis .. Schonlein-Henoch allergic ..I http://pmj.bmj.com/ experimental analogous disease the earliest lesion, Hypersensitivity angiitis .. .. .. I in guinea-pig, is oedema (Long, 1954, I955), and Allergic granulomatous angiitis .. ..I Pulmonary lupus .. .. .. .. .. 2 this is shown in rheumatoid arthritis (Kulka et al., Allergic polyradiculoneuritis .. .. 4 1955) which is soon associated with cellular Spontaneous acute disseminated encephalo- infiltration and vascular insult. myelitis: (a) Myelitis type .. .. .. 3 Neurological Complications in (b) Encephalomyelitis type .. .. 2 Glandular fever syndrome.. .. .. I- Hypersensitivity Meningococcal meningitis .. .. .. .. on October 2, 2021 by guest. Protected Mayo Clinic has played an important role in Drugs allergy .. .. .. .. .. 2 advancing the knowledge of lupus. Clark and Bailey (I956), of the same institute, have drawn 21 attention to the frequency with which mental and TABLE 2 No. of neurological complications occur in this disease. Hypersensitivity States cases They reviewed the neurological complications in Upper respiratory tract non-specific infections io systemic lupus observed at Mayo Clinic; these Asthma with eosinophilia (48% in one case) (io% in other case) .. .. .. .. .. 2 included convulsions, mental disease, hemiplegia, Meningococcal infection .. .. .. .. polyneuritis, subarachnoid haemorrhage, vertigo, Staphylococcal .. .. .. .. .. nystagmus, chorea, monoplegia. Pathological Streptococcal .. .. .. .. .. study revealed widespread vascular lesions in the Drugs allergy .. .. .. .. .. central nervous system. Similar neurological Unknown .. .. .. .. .. .. 4 complications have also been observed in poly- ZI arteritis. Postgrad Med J: first published as 10.1136/pgmj.33.377.121 on 1 March 1957. Downloaded from March 1957 FAZLULLAH: Neurological Complications in Hvpersensitivity 123 TABLE 3 was maintained for a further six weeks. Two No. of Neurological disorders cases months later she was seen when complete regres- Neuropathies: sion of the transverse myelitis was found. C.S.F. (a) Symmetrical polyneuritis in the legs 3 was normal, except raised proteins