{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:41:43Z","timestamp":1756993303450},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"462","license":[{"start":{"date-parts":[[1964,4,1]],"date-time":"1964-04-01T00:00:00Z","timestamp":-181526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1964,4,1]]},"DOI":"10.1136\/pgmj.40.462.209","type":"journal-article","created":{"date-parts":[[2008,12,29]],"date-time":"2008-12-29T20:16:16Z","timestamp":1230581776000},"page":"209-211","source":"Crossref","is-referenced-by-count":1,"title":["Idiopathic Acquired Hypogammaglobulin\u00e6mia with Melanosis, Associated with Sibship Immunoglobulin Abnormalities and Ankylosing Spondylitis"],"prefix":"10.1093","volume":"40","author":[{"given":"B I","family":"Hoffbrand","sequence":"first","affiliation":[{"name":"University College Hospital Medical Registrar, , Londor, W.C. 1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1964,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/000331975901000418","article-title":"Clinical Observations in the Treatment of Phlebo-Thrombosis with Fibrinolysin","volume":"1","author":"CARROL, B.J.","year":"1959","unstructured":"CARROL, B. J. (1959): Clinical Observations in the Treatment of Phlebo-Thrombosis with Fibrinolysin, Angiology, 1O, 308.","journal-title":"Angiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/0002-9149(60)90341-6","article-title":"Review of Clinical Experience with Clot-lysing Agents, Amer","volume":"6","author":"CLIFFTON, E.E.","year":"1960","unstructured":"CLIFFTON, E. E. (1960): Review of Clinical Experience with Clot-lysing Agents, Amer. Y. Cardiol., 6, 476.","journal-title":"Y. Cardiol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/00000658-195401000-00006","article-title":"Lvsis of Thrombi Produced by Sodium Morrhuate in Femoral Vein of Dogs by Human Plasmin (Fibrinolysin)","volume":"139","author":"GROSSI, C.E.; CANNAMELA, D.A.","year":"1954","unstructured":"-, GROSSI, C. E., and CANNAMELA, D. A. (1954): Lvsis of Thrombi Produced by Sodium Morrhuate in Femoral Vein of Dogs by Human Plasmin (Fibrinolysin), Ann. Surg., 139, 52.","journal-title":"Ann. Surg"},{"key":"ref_4","article-title":"Treatment of Peripheral Arterial Occlusion by Streptokinase Perfusions, Brit","volume":"508","author":"McNICOL, G.P.; REID, W.; BAIL, W.H.; DOUGLAS, A.S.","year":"1963","unstructured":"McNICOL, G. P., REID, W., BAIL, W. H., and DOUGLAS, A. S. (1963): Treatment of Peripheral Arterial Occlusion by Streptokinase Perfusions, Brit. med. J., i, I508.","journal-title":"med. J"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1177\/000331975901000420","article-title":"Clinical Observations in Thrombo-embolic Disease Treated with Fibrinolysin","volume":"10","author":"MOSER, K.M.","year":"1959","unstructured":"MOSER, K. M. (1959): Clinical Observations in Thrombo-embolic Disease Treated with Fibrinolysin,Anniology, 10, 319.","journal-title":"Anniology"},{"key":"ref_6","article-title":"Feasibility of Adequate Thrombolytic Therapy with Streptokinase in Peripheral Arterial","volume":"499","author":"VERASTRAETE, M.; A., A.M.E.R.Y.; VERMYLAN, J.","year":"1963","unstructured":"VERASTRAETE, M., AMERY A., and VERMYLAN, J. (1963): Feasibility of Adequate Thrombolytic Therapy with Streptokinase in Peripheral Arterial Occlusions, Brit. med. Y., i, I499.","journal-title":"Occlusions, Brit. med. Y"},{"key":"ref_7","article-title":"quantitative abnormalities of the serum immunoglobulins have been found in the families of cases of idiopathic acquired hypogammaglobulinaemia (Fudenberg, Franklin, German and Kunkel, I962). A significantly higher than normal incidence of rheumatoid factor and of frank rheumatoid arthritis has also been found in these families","author":"Recently","year":"I962).","unstructured":"Recently, quantitative abnormalities of the serum immunoglobulins have been found in the families of cases of idiopathic acquired hypogammaglobulinaemia (Fudenberg, Franklin, German and Kunkel, I962). A significantly higher than normal incidence of rheumatoid factor and of frank rheumatoid arthritis has also been found in these families (Fudenberg and others, I962; Good, Kelly, Rotstein and Varco, I962)."},{"key":"ref_8","article-title":"The following case of idiopathic acquired hypogammaglobulin2emia demonstrates familial abnormalities of the immunoglobulins. There are, in addition, two previously unrecorded features. In the first place, a brother who has abnormal immunoglobulins, has ankylosing spondylitis. This occurrence is of interest in view of the high frequency of rheumatoid arthritis in the families of Fudenberg and others (1962), and the controversial relationship of the two forms of arthritis. In the second place, the patient had marked diffuse melanosis and vitiligo","unstructured":"The following case of idiopathic acquired hypogammaglobulin2emia demonstrates familial abnormalities of the immunoglobulins. There are, in addition, two previously unrecorded features. In the first place, a brother who has abnormal immunoglobulins, has ankylosing spondylitis. This occurrence is of interest in view of the high frequency of rheumatoid arthritis in the families of Fudenberg and others (1962), and the controversial relationship of the two forms of arthritis. In the second place, the patient had marked diffuse melanosis and vitiligo."},{"key":"ref_9","article-title":"In 1958, he was admitted to another hospital with an exacerbation of his chest symptoms of eleven weeks duration. He was found to have partial collapse of the lower lobes of the lungs, with bilateral hilar lymphadenopathy and hepatosplenomegaly. He was thought at this time to be slightly hyper-pigmented. Routine investigations were non-contributory, although serum protein electrophoresis showed a marked reduction of the gammaglobulin level. The patient refused any biopsy procedure, and a presumed diagnosis of Hodgkin's Disease was made. The chest infection responded to routine treatment. Radiotherapy was given to the mediastinum, with a subsequent reduction in the size of the hilar glands","unstructured":"In 1958, he was admitted to another hospital with an exacerbation of his chest symptoms of eleven weeks duration. He was found to have partial collapse of the lower lobes of the lungs, with bilateral hilar lymphadenopathy and hepatosplenomegaly. He was thought at this time to be slightly hyper-pigmented. Routine investigations were non-contributory, although serum protein electrophoresis showed a marked reduction of the gammaglobulin level. The patient refused any biopsy procedure, and a presumed diagnosis of Hodgkin's Disease was made. The chest infection responded to routine treatment. Radiotherapy was given to the mediastinum, with a subsequent reduction in the size of the hilar glands."},{"key":"ref_10","article-title":"Total serum protein was 4.4 g.\/Ioo ml., with electrophoresis showing a small reduction of the albumin, a small increase of the a, globulin, and a virtual absence of the gamma globulin levels. Gel-diffusion precipitin estimation","volume-title":"confirmed the severe hypogammaglobulinemia, with a level of 2.5 mg.\/ioo","author":"ml., the","year":"1957","unstructured":"Total serum protein was 4.4 g.\/Ioo ml., with electrophoresis showing a small reduction of the albumin, a small increase of the a, globulin, and a virtual absence of the gamma globulin levels. Gel-diffusion precipitin estimation (Gell, 1957) confirmed the severe hypogammaglobulinemia, with a level of 2.5 mg.\/ioo ml., the"},{"key":"ref_11","article-title":"Special stains of the skin sections excluded causes of pigmentation, other than melanin. Histology of the spleen and lymph glands showed replacement of the normal architecture by large pale reticulum cells. The liver showed 'nutmeg' changes only. In all the tissues examined, there was a complete absence of plasma cells. The histological findings thus confirmed the diagnosis of idiopathic acquired hypogammaglobulinemia","year":"1962","unstructured":"Special stains of the skin sections excluded causes of pigmentation, other than melanin. Histology of the spleen and lymph glands showed replacement of the normal architecture by large pale reticulum cells. The liver showed 'nutmeg' changes only. In all the tissues examined, there was a complete absence of plasma cells. The histological findings thus confirmed the diagnosis of idiopathic acquired hypogammaglobulinemia (Martin, 1962)."},{"key":"ref_12","article-title":"The patient's brother is a medical practitioner, bom in I909. He complained of backache in I953 at the age of 44. An x-ray showed bilateral sacro-iliitis (Fig. I). A diagnosis of early ankylosing spondylitis was made, and a course of radiotherapy to his back relieved the symptoms. He has never had evidence of peripheral arthritis, or symptoms of conjunctivitis, urethritis or colitis","unstructured":"The patient's brother is a medical practitioner, bom in I909. He complained of backache in I953 at the age of 44. An x-ray showed bilateral sacro-iliitis (Fig. I). A diagnosis of early ankylosing spondylitis was made, and a course of radiotherapy to his back relieved the symptoms. He has never had evidence of peripheral arthritis, or symptoms of conjunctivitis, urethritis or colitis."},{"key":"ref_13","article-title":"The patient's sister was born in 1907, and is alive and well. Each of the patient's siblings has two children in their late teens, without significant past or present medical history","unstructured":"The patient's sister was born in 1907, and is alive and well. Each of the patient's siblings has two children in their late teens, without significant past or present medical history."},{"key":"ref_14","article-title":"have reyiewed the genetics of the hereditary human gamma globulin types. The immunoglobulin abnormalities, found in the first-degree relatives of patients with idiopathic acquired hypogammaglobulineemia, are assumed to depend on aberrations of production, in the heterozygous state, of particular immunoglobulin structural sub-units. They believe the high incidence of rheumatoid factor in these relatives is an associated feature of the gene defect. The high incidence of frank rheumatoid arthritis in these relatives","author":"Fudenberg; Franklin","year":"1963","unstructured":"Fudenberg and Franklin (1963) have reyiewed the genetics of the hereditary human gamma globulin types. The immunoglobulin abnormalities, found in the first-degree relatives of patients with idiopathic acquired hypogammaglobulineemia, are assumed to depend on aberrations of production, in the heterozygous state, of particular immunoglobulin structural sub-units. They believe the high incidence of rheumatoid factor in these relatives is an associated feature of the gene defect. The high incidence of frank rheumatoid arthritis in these relatives (Fudenberg and others, I962) is presumably also explained in this wiay."},{"key":"ref_15","article-title":"The consensus of opinion, certainly in this country, is that ankylosing spondylitis and rheumatoid arthritis are different diseases (Short, Bauer and Reynolds, 1957). If, however, the incidence of ankylosing spondylitis in the families of cases of idiopathic acquired hypogammaglobulinaemia proves to be raised, similarly to that of rheumatoid arthritis in these circumstances, it would be highly suggestive of a common oetiological factor, presumably genetic, between the two forms of arthritis","unstructured":"The consensus of opinion, certainly in this country, is that ankylosing spondylitis and rheumatoid arthritis are different diseases (Short, Bauer and Reynolds, 1957). If, however, the incidence of ankylosing spondylitis in the families of cases of idiopathic acquired hypogammaglobulinaemia proves to be raised, similarly to that of rheumatoid arthritis in these circumstances, it would be highly suggestive of a common oetiological factor, presumably genetic, between the two forms of arthritis."},{"key":"ref_16","first-page":"but","article-title":"There was no evidence, in this case, of an endocrine cause of melanosis. There was also no evidence of steatorrhcea, which is a known complication of hypogammaglobulinemia (Cooke, Weiner and Shinton, I957) and in which melanosis is well recognized (Wells, I962). Antimitotic drug administration may have contributed to the severity of the melanosis (Brit. med","volume":"963","unstructured":"There was no evidence, in this case, of an endocrine cause of melanosis. There was also no evidence of steatorrhcea, which is a known complication of hypogammaglobulinemia (Cooke, Weiner and Shinton, I957) and in which melanosis is well recognized (Wells, I962). Antimitotic drug administration may have contributed to the severity of the melanosis (Brit. med. J., I963), but the skin changes were undoubtedly present before such therapy was first instituted.","journal-title":"J; the skin changes were undoubtedly present before such therapy was first instituted"},{"key":"ref_17","article-title":"Little is known of the etiology of non-endocrine melanosis, associated with systemic diseases. A large proportion of these diseases, such as kala-azar, Gaucher's Disease, Felty's Syndrome, Hodgkin's Disease and others (Sutton, I956), have in common marked reticulo-endothelial involvement and hyperplasia. By analogy, it seems possible that the melanosis of the patient reported here was, in some as yet inexplicable way, related to his marked reticulum cell hyperplasia","unstructured":"Little is known of the etiology of non-endocrine melanosis, associated with systemic diseases. A large proportion of these diseases, such as kala-azar, Gaucher's Disease, Felty's Syndrome, Hodgkin's Disease and others (Sutton, I956), have in common marked reticulo-endothelial involvement and hyperplasia. By analogy, it seems possible that the melanosis of the patient reported here was, in some as yet inexplicable way, related to his marked reticulum cell hyperplasia."},{"key":"ref_18","first-page":"1148","article-title":"Agammaglobulinoemia with Splenonegaly, Brit","volume":"i,","author":"CITRON, K.M.","year":"1957","unstructured":"CITRON, K. M. (1957): Agammaglobulinoemia with Splenonegaly, Brit. med. Y., i, 1148.","journal-title":"med. Y"},{"key":"ref_19","article-title":"Agammaglobulinmmia: Report of Two Adult","volume":"115","author":"COOKE, W.I.; WEINER, W.; SHINTON, N.K.","year":"1957","unstructured":"COOKE, W. I., WEINER, W., and SHINTON, N. K. (1957): Agammaglobulinmmia: Report of Two Adult Cases, Ibid., i, 115I.","journal-title":"Cases, Ibid"},{"key":"ref_20","first-page":"565","article-title":"Human Gamma Globulin, Genetic Control and Its Relation to Disease, Ann","volume":"58","author":"FUDENBERG, H.; FRANKLIN, E.C.","year":"1963","unstructured":"FUDENBERG, H., and FRANKLIN, E. C. (1963): Human Gamma Globulin, Genetic Control and Its Relation to Disease, Ann. intern. Med., 58, 17I. GERMAN, J. L., and KUNKEL, H. G. (1962): The Occurrence of Rheumatoid Factor and Other Abnormalities in Families of Patients with Agammaglobulinemia, Arthr. and Rheum., 5, 565.","journal-title":"intern. Med; The Occurrence of Rheumatoid Factor and Other Abnormalities in Families of Patients with Agammaglobulinemia, Arthr"},{"key":"ref_21","first-page":"67","article-title":"The Estimation of the Individual Human Serum Proteins by an Immunological Method, 5t. clin","volume":"1","author":"GELL, P.G.H.","year":"1957","unstructured":"GELL, P. G. H. (1957): The Estimation of the Individual Human Serum Proteins by an Immunological Method, 5t. clin. Path., 1O, 67.","journal-title":"Path"},{"key":"ref_22","first-page":"272","article-title":"In 'Progress in Allergy'","volume":"6","author":"GOOD, R.A.; KELLY, W.D.; ROTSTEIN, J.; VARcO, R.L.","year":"1962","unstructured":"GOOD, R. A., KELLY, W. D., ROTSTEIN, J., and VARcO, R. L. (1962): In 'Progress in Allergy', vol. 6, ed. Kallos, P., and Waksman, B. H., P. 272. Basel, New York: Karger."},{"key":"ref_23","first-page":"398","article-title":"Some Morphological Considerations in Hypogammaglobulin2emia, Proc","volume":"55","author":"MARTIN, N.H.","year":"1962","unstructured":"MARTIN, N. H. (1962): Some Morphological Considerations in Hypogammaglobulin2emia, Proc. roy. Soc. Med., 55, 398.","journal-title":"roy. Soc. Med"},{"key":"ref_24","article-title":"Rheumatoid Arthritis","author":"SHORT, C.L.; BAUER, W.; REYNOLDS, W.E.","year":"1957","unstructured":"SHORT, C. L., BAUER, W., and REYNOLDS, W. E. (1957): 'Rheumatoid Arthritis'. Cambridge, Mass.: Harvard Univ. Press."},{"key":"ref_25","article-title":"'Diseases of the Skin'. iith edition","author":"SUTTON, R.L.","year":"1956","unstructured":"SUTTON, R. L. (1956): 'Diseases of the Skin'. iith edition. London: Kimpton."},{"key":"ref_26","first-page":"937","article-title":"Skin Disorders in Relation to Malabsorption, Brit","volume":"ii,","author":"WELLS, G.C.","year":"1962","unstructured":"WELLS, G. C. (1962): Skin Disorders in Relation to Malabsorption, Brit. med. Y'., ii, 937.","journal-title":"med. 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