Proc. roy. Soc. Med. Volume 68 July 1975
The cryoglobulin precipitates out at a rather high temperature (28-30°C) which explains the initial laboratory abnormalities when blood was allowed to clot at temperatures below 28°C and the patient was found to have hypogammaglobulinwmia and hypocomplementTemia. The symptomatology early on in her illness (polyarthritis and vasculitis) was related to cold and can be attributed to the cryoglobulin. Her paraproteins including the cryoglobuiins have been removed by plasmaphoresis using an AMINCO blood separator (Dr C J Oon, Westminster Hospital), with good results. Serial estimations of the cryoglobulin levels following plasmaphoresis showed a gradual rise indicative of a slow-growing im.munocytoma - a good prognostic sign as these usually respond well to chemotherapy - and is consistent with the patient's prolonged history.
Acknowledgment: We are grateful to Dr J F Mowbray for help in investigation of this patient.
16 The following cases were also presented: Sarcoidosis with Widespread Pruritic Scaling Erythroderma Dr H R Vickers Reticular Erythematous Mucinosis Syndrome Dr R Kubba (for Dr R H Champion) Atypical Annular Necrobiosis Lipoidica of the Face Dr Roger Clayton (for Dr M Feiwel) ? Bullous Lichen Planus. ? Cicatricial Pemphigoid Dr Sheila Powell (for Dr H R Vickers and Dr T J Ryan) Lupus Erythematosus Panniculitis Dr P P Seah (for Dr M Feiwel) Lymphangio-endothelioma Dr J R S Rendall (for Dr H R Vickers and Dr T J Ryan) Periorbital Necrotizing Fasciitis with Polymyositis Dr J A Carruthers (for Dr E Cronin and Mr P Wright)
Meeting 16 January 1975
Cases Lymphomatoid Granulomatosis D M MacDonald MB MRCP (for D I Williams MB FRCP) (Department of Dermatology, King's College Hospital, Denmark Hill, London SE5 9RS) A H, male aged 75 History: Two years previously developed widespread rash comprising bluish red diffuse nodules on a background of generalized ichthyosis. Had noticed increasing dyspncea, frequent bronchitis, lassitude and abdominal discomfort for two to three years. Two episodes of thrombophlebitis had occurred in the previous three years. For two years an altered mental state had been observed becoming increasingly irascible, with angry outbursts, episodes of confusion and loss of memory. On examination: Widespread plum-coloured infiltrated lesions of the skin with generalized ichthyosis. Small lymph nodes in axille and left groin. No hepatosplenomegaly. Impaired cerebral cortical function. Mild sensory peripheral neuro-
Skin histology: Dense focal granulomatous infiltrate centred partly on sweat glands, and extending into subjacent adipose tissue. Non-
caseating giant cell granulomas are prominent together with collections of lymphocytes, plasma cells and histiocytes. Many small blood vessels are occluded by thrombus and show fibrinoid change. Sweat gland epithelium hyperplastic, reminiscent of salivary glands in Sjogren's disease. The combination of features suggests lymphomatoid granulomatosis. Chest X-ray and tomograms: Masses in right lower and left upper zones confirmed to be intrapulmonary. Hilar nodes normal. Bone marrow, lymphangiograms, sinus and skull X-rays normal. Blood count, urea and electrolytes, creatinine clearance, liver function tests, plasma proteins normal. Lung biopsy, peripheral nerve biopsy and intravenous pyelography refused by patient. Progress: The patient was initially treated with prednisone 40 mg daily. On this regime the skin lesions became less infiltrated, pruritus abated and many lesions resolved. The well-defined masses in the lungs disappeared, to be replaced by a picture of consolidation in the right lower zone. The psychotic features deteriorated, however. On reduction of prednisone to 20 mg daily the skin lesions became obvious once more while masses reappeared on chest X-ray. On increase of the dose to 50 mg daily, the clinical picture has again improved, although psychotic behaviour poses a
Section of Dermatology
Comment Lymphomatoid granulomatosis was defined by Liebow et al. (1972). It is a vasculitic angiodestructive granulomatous and lymphoreticular proliferative disease. Although considered probably to be a separate disease entity it shares many features with so-called limited forms of Wegener's granulomatosis (Carrington & Liebow 1966, Liebow & Carrington 1969, Cassan et al. 1970). In lymphomatoid granulomatosis the lungs are involved in more than 90 % of cases and skin involvement is seen in 45 %; the kidneys are affected in 45 % but without glomerulitis. Central nervous system disease occurs in 15 % of cases and peripheral neuropathy in a further 15 %; 60 % of cases have been fatal within five years. A small number have progressed to true lymphoma. Both lung and skin lesions (which may be the first manifestation) may resolve spontaneously or with steroid treatment. Diagnosis depends on the typical histological features in association with the clinical picture. It is suggested that electron microscopic appearances may be characteristic (Kay et al. 1974). [To be published more fully elsewhere.]
Dr I Sarkany: I showed a patient at this Section under the title of 'Patchy Alopecia, Anhidrosis, Eccrine Gland Wall Hypertrophy and Vasculitis' in 1969 and again in 1970. Lymphomatoid granulomatosis (Liebow) had not then been described, but the clinical features, histology and course of my patient's disease clearly fit in with the picture later delineated by Liebow. During the next two years, gradual extension of the bald anhidrotic patches took place and he eventually developed generalized glandular enlargement, clinically and histologically characteristic of Hodgkin's disease. After temporary improvement as a result of quadruple therapy, he went downhill and died in 1972.
REFERENCES Carrington C B & Liebow A A (1966) American Journal of Medicine 41, 497 Cassan S M, Coles D T & Harrison E G (1970) American Journal of Medicine 49, 366 Kay S, Fu Y, Minars N & Brady J W (1974) Cancer 34, 1675 Liebow A A & Carrington C B (1969) American Journal ofPathology 55, 78a Liebow A A, Carrington C R B & Friedman P J (1972) Human Pathology 3, 457
REFERENCES Sarkany I (1969) Proceedings of the Royal Society of Medicine 62, 1 57 (1970) Proceedings of the Royal Society of Medicine 63, 888
Dr A G Stansfeld: The sweat gland lesion in this case resembles the changes in the salivary glands in the Mikulicz-Sjogren syndrome. Both show epithelial and myoepithelial proliferation in the ducts accompanied by an immune-type cellular reaction. Arteritis is a recognized feature in Sjogren's syndrome also. There appears to be a spectrum of overlapping syndromes in this area, of which this case is an admirable illustration. Dr H R Vickers: I wonder why Wegener's granulomatosis should be incorporated in the spectrum of this condition. In Wegener's granulomatosis the skin changes are due entirely to involvement of the blood vessels and bear no resemblance whatsoever to those seen in the patient presented today. The proposed spectrum is too wide. Dr D M MacDonald: Wegener's granulomatosis is included in the spectrum because it shares with lymphomatoid granulomatosis the features of vasculitis and granuloma formation. Liebow considers that there may be common etiological factors. In certain cases lymphomatoid granulomatosis can be almost indistinguishable from the limited forms of Wegener's granulomatosis.
Dr R J Cairns: Lymphomatoid granulomatosis (Liebow) appears to be a rather pleomorphic reticulogranuloma (pseudolymphoma) that sometimes becomes frankly malignant, and it may provide a clue to the enigmatic relationship between autoimmune disease and lymphoma. First, there may be a parallel between Sjogren's syndrome and this recently described disease; both may involute spontaneously or show steroid responsiveness, and yet both may progress and become an uncontrolled lymphoma, Mycosis Fungoides in a Patient such as lymphosarcoma. A search, therefore, for any Following Two Lymphomata evidence that might suggest an autoimmune mechanism at work in the early stages of the process is P J Marriott MRCP, A G Stansfeld FRcPath important. The early and peculiar involvement of and D D Munro FRCP sweat glands, a known target for immunological (St Bartholomew's Hospital, London EC]) action in Sjogren's (sicca) syndrome, may be significant. Another parallel is perhaps with the rare S H, male aged 65. Retired gardener 'malignant' nasal granuloma, an essentially histio- History: Presented in September 1974 with a cytic granuloma that is probably immunologically four-months rash on his legs. His only symptom controlled until it becomes lymphomatous. One might was mild pruritus. ask whether T-cell function is impaired early in the disease, permitting clonal proliferation, with features Past history: In 1954 he had a right-sided parotid of both autoimmune disease and lymphoma occurring swelling also involving his hard palate. Histology as an escape phenomenon. Alternatively, is it related of two large biopsies showed malignant lymphoma in some way to mycosis fungoides, itself a puzzling and the region was treated with radiotherapy as disorder which behaves more like a granuloma than also were clinical recurrences in 1960 in the a true malignancy? anterior ethmoid region and over the left scapula