Sarcoid Granulomata Research Articles

ODP106 Mystery of the Calcium: A Case of Exclusive Cutaneous Sarcoidosis presenting with Symptomatic Hypercalcemia

Abstract The skin is the second most involved organ after the lung in sarcoidosis. It could be an early manifestation that may progress to systemic disease later. Exclusive cutaneous disease is more frequently seen in females. Specific lesions include erythema nodosum, skin plaques, subcutaneous nodules, maculopapular rashes, lupus pernio, scar lesions, and psoriasiform lesions. Most with cutaneous sarcoidosis need no treatment unless there is associated cosmetic disfigurement. We present a unique case of cutaneous sarcoidosis presenting with symptomatic hypercalcemia without systemic disease. A 75-year-old African American female was admitted with generalized weakness. She had no other symptoms. On arrival, she was bradycardic with other normal vitals. Physical examination was normal. EKG showed sinus bradycardia with RBBB. She was found to have AKI with creatinine of 4.3 mg/dL (0.6-1.3 mg/dL) and a corrected calcium of 12.2 mg/dL (8.6-10.2 mg/dL). TSH was 4.64 uIU/mL (0.35-5.50 uIU/mL). Chest X-ray showed no abnormalities. Renal ultrasound revealed bilateral medical renal disease, with several non-obstructing calculi in the right kidney. The patient was managed with intravenous fluids. Her creatinine improved to 3.1 mg/dL; however, the calcium remained elevated at 11.8 mg/dL. PTH was 31 pg/mL (12-88 pg/mL) and urine 24-hr calcium was elevated at 470 mg (35-250 mg). 25-OH vitamin D level was 40 ng/mL (30-100 ng/mL). With no response to intravenous hydration, IV bisphosphonates were initiated. Despite that, her calcium remained at 11.9 mg/dL. On obtaining a more detailed history, it was revealed that a skin punch biopsy performed six years prior showed sarcoid granulomatous dermatitis. The 1, 25 dihydroxy vitamin D was 93 pg/mL (20-79 pg/mL). The ACE level was high at 64 U/L (8-52 U/L). CT chest showed no evidence of granulomatous disease, including the absence of hilar adenopathy. The patient was started on prednisone 20 mg/day. Her calcium trended down to 10.7 mg/dL over the next three days. Although cutaneous sarcoidosis may not be life-threatening, it may have substantial psychological and social impacts. Hypercalcemia is a high prevailing complication of systemic sarcoidosis. It occurs due to the uncontrolled synthesis of 1,25-OH D3 by macrophages in the sarcoid granulomata. As a result, there is increased calcium absorption in the intestine and calcium resorption in the bone. Glucocorticosteroids act by inhibiting the 1alpha-hydroxylase activity of macrophages. Prednisone 20 to 40 mg/day followed by a taper is the recommended dose. Other medications that may be used include antimalarials, thalidomide, methotrexate, and other immunomodulatory agents. Hypercalcemia in a patient with cutaneous sarcoidosis and no pulmonary involvement is a rare presentation. It is essential to recognize that long-term follow-up is advised for those with cutaneous sarcoidosis, as some may develop systemic involvement subsequently. Presentation: No date and time listed

EP20 Hypercalcaemia in sarcoidosis

Case report - IntroductionSarcoidosis often classically presents as Lofgren’s syndrome in up to 30% of cases, a triad of erythema nodosum, bilateral hilar lymphadenopathy and polyarthritis. However, the lack of identification and awareness of extrapulmonary manifestations of sarcoidosis can often lead to delayed diagnosis and treatment. In sarcoidosis, hypercalcaemia is a feature in only 10-20% of all cases. However, the manifestation of hypercalcaemia may be the first presentation of sarcoidosis in patients who do not show the classical features of acute sarcoidosis. Case report - Case descriptionA 38-year-old man presented with a 5-month history of profound fatigue, poor concentration, and non-specific joint pains. He reported earlier swelling of his ankles and feet. He had lost 1 stone in weight over the last month. There was no history of fever or night sweats. He smoked 10 cigarettes per day but was otherwise fit and well. On examination urine dipstick testing was negative. There was no evidence of lymphadenopathy. Cardio-respiratory and abdominal examinations were unremarkable. Examination of his skin and joints was also unremarkable. There was mild non-tender ankle oedema.His first blood tests showed a raised adjusted calcium of 3.25 and a raised white cell count of 11.8, with an eosinophilia of 0.75. Other preliminary blood results were unremarkable (normal Hb, U+Es, LFTs, CRP, ESR, RF, anti-CCP, ANA and TFTS). His chest X-ray was reported as clear.His PTH was appropriately suppressed and vitamin D level was adequate with normal urinary calcium and normal serum protein electrophoresis. Serum ACE level was raised at 114 (normal 8-52). PTH related peptide test was not available.A CT chest abdomen and pelvis scan carried out to rule out malignancy was normal with no notable lymphadenopathy. A subsequent PET CT scan was normal. Acutely, his hypercalcaemia was treated with IV fluids and IV pamidronate. Although his calcium rapidly normalised, he reported feeling only 10% better. He complained of ongoing ankle pain. An MRI scan of both ankles with contrast showed mild synovitis of ankle, subtalar and talonavicular joints. There was also evidence of tenosynovitis.Given the constellation of hypercalcaemia, raised serum ACE level and ankle synovitis on MRI scan, he was treated for sarcoidosis with prednisolone 20mg. This led to a rapid improvement in his symptoms and normalisation of serum ACE. He was started on azathioprine as a steroid-sparing agent. Case report - DiscussionIn cases series, hypercalcaemia due to sarcoidosis accounts for only 6% of all hypercalcaemic patients. The mechanism of hypercalcaemia in sarcoidosis is thought to be via activated pulmonary macrophages and sarcoid lymph node granulomas which upregulate the enzyme 1-alpha hydroxylase, resulting in the increased formation of calcitriol (1,25(OH)2D3). This increases calcium absorption from the gastrointestinal tract, stimulates renal calcium reabsorption and promotes calcium release from skeletal stores, causing hypercalcaemia.This case was particularly unusual as earlier literature suggests that sarcoidosis-associated hypercalcaemia is a result of activated pulmonary macrophages and sarcoid granulomas. However, this patient had significant hypercalcaemia without any radiological lung involvement or granulomata, posing the question whether there are other pathways causing hypercalcaemia in sarcoidosis. Hypercalcaemia without pulmonary involvement may be due to the presence of small amounts of sarcoid granulomata in extra-pulmonary locations such as the porta hepatis. These may not be as easily detectable on radiological investigations but may contribute to the upregulation of 1-alpha hydroxylase and subsequent hypercalcaemia. Another explanation for the significant hypercalcaemia in this patient may be due to the production of parathyroid hormone-related peptide (PTHrP) from sarcoid granulomas and bone marrow, which upregulates renal 1-alpha hydroxylase enzymes and increases the formation of calcitriol.There was no area to obtain a tissue biopsy given the normal CT and PET CT scans, resulting in a greater reliance on history, examination, and serological investigations. In addition, 30-50% of all patients with sarcoidosis have hypercalciuria, yet this patient interestingly had only an isolated hypercalcaemia with a normal urinary calcium. Case report - Key learning points Hypercalcaemia is rare in the absence of pulmonary involvement with only 10 cases reported in literature.Although non-specific, an elevated serum ACE level may be a useful pointer to the diagnosis of sarcoidosis in the absence of other classical signs.In this case, granulomatous tissue responsible to produce 1,25(OH)2D3 might be below the limits of radiological detection. Production may originate from extra-pulmonary sarcoid granulomatous tissue such as in the porta hepatis. Another possible mechanism for hypercalcaemia may be the production of PTHrP which has been reported in sarcoid tissue specimens and in the bone marrow.

A Case of Immune-Mediated Necrotizing Myopathy With Associated Skeletal Muscle Involvement by Sarcoid Granulomata: A Rare Association

Abstract Skeletal muscle involvement by noncaseating granulomata occurs in a variety of conditions, including sarcoidosis, infections, and rarely in association with primary inflammatory myopathies such as inclusion body myositis (IBM) and dermatomyositis (DM). Sarcoid myopathy is typically asymptomatic; however, a picture of acute myositis with proximal muscle weakness has been described. Immune-mediated necrotizing myopathy (IMNM) is a subgroup of inflammatory myopathies typically presenting with proximal muscle weakness and markedly elevated muscle enzymes, mostly occurring in the setting of statin treatment. IMNM is associated with positive autoantibodies, but a subset of cases is antibody negative. Here we describe a case of myopathy occurring in association with sarcoidosis with combined features of granulomatous and necrotizing myopathy. The patient was a 54-year-old African American male with medical history significant for statin use 3 years ago, which was discontinued due to myalgia and elevated muscle enzymes and biopsy-proven sarcoidosis diagnosed on a pulmonary lymph node biopsy. He presented with progressive worsening of bilateral proximal weakness involving the upper and lower extremities. Electromyogram showed features of active myopathy with no evidence of peripheral neuropathy. Myositis panel was negative for the following antibodies: anti-Jo1, Mi-2, anti-Ku, PL-7, PL-12, OJ, EJ, and SRP. However, there was elevation of aldolase, CRP, and CK-MB. Biopsy of thigh and deltoid muscle showed necrotic muscle fibers, myophagocytosis with associated minimal inflammation, and multiple well-formed nonnecrotizing granulomas with multinucleated giant cells. Myopathic features include increased internalized nuclei, round atrophic fibers, and scattered split fibers. Specific features of IBM or DM were not present. Conclusion Myopathies developing or worsening after discontinuation of statin are rare. The association of necrotizing myopathy with sarcoidosis is not well described in the literature. Additional studies are warranted to elucidate this association.

Sarcoïdose pulmonaire apparue sous étanercept

TNF blockers are widely used to treat inflammatory rheumatic diseases and also in the treatment of extrapulmonary sarcoidosis. TNFα plays a major role in the development and persistence of sarcoid granulomata. However, recent studies have reported the involvement of anti-TNF therapies in the development of granulomatosis associated with the clinical and radiological features of sarcoidosis.A 54-years-old man with ankylosing spondylitis was treated with etanercept for two years. He was admitted with symptoms of bronchitis associated with radiological evidence of bilateral pulmonary nodules and a right upper lobe infiltrate. Anti-TNF therapy was stopped even though the patient had received 3 months of prophylactic treatment with rifampicin and isoniazid before starting etanercept. Bronchoalveolar lavage excluded infection, particularly tuberculosis. The chest CT-scan showed bilateral pulmonary nodules with peribronchovascular micronodules and enlarged mediastinal lymph nodes. Surgical lung biopsy was performed and revealed non-caseating granulomata. All the data were consistent with a diagnosis of pulmonary sarcoidosis. The patient remained symptomatic despite discontinuation of etanercept for ten months. Corticosteroids were then introduced, leading to a clinical, functional and radiological improvement.This case report underlines the importance of studying the pulmonary complications of TNF blockers. The first priority is to exclude tuberculosis but a diagnosis of sarcoid-like granulomatosis has to be considered. Twenty-three cases have been described in the literature to date.

Treatment of therapy-resistant sarcoidosis with adalimumab

A possible role of tumor necrosis factor alpha (TNFalpha) in the pathomechanism of sarcoidosis must be considered in the analysis of this disorder since elevated concentrations of this cytokine have been found. In addition, TNFalpha expression could be demonstrated in sarcoid granulomata [1]. It is well known that TNFalpha plays a crucial role in granulomatous inflammation, e.g., in mycobacterial diseases [2]. Therefore, TNFalpha blockade is a potential approach in the therapy for sarcoidosis. Up to now, various cases of therapy-resistant sarcoidosis treated with anti-TNFalpha (infliximab and etanercept) have been reported [3-8]. Here, we describe successful treatment using adalimumab, a human recombinant immunoglobulin (Ig) G1 anti-TNF monoclonal antibody [9].

Sarcoidosis occurring after interferon‐α therapy for chronic hepatitis C: Report of two cases

We report two patients who were diagnosed with sarcoidosis after receiving interferon (IFN)-alpha therapy for chronic hepatitis C, and conduct a review the relevant literature. The first patient was a 52-year-old female who developed multiple subcutaneous nodules 2 months after finishing IFN-alpha therapy. A skin biopsy from subcutaneous nodules on the right elbow joint revealed sarcoid granulomata. These lesions resolved spontaneously 4 months later. The second patient, a 57-year-old male, developed bilateral hilar and mediastinal lymph node enlargement 2 years after finishing IFN-alpha 2a therapy. A transbronchial lung biopsy demonstrated sarcoid granulomata. In addition, he had uveitis and left ulnar nerve involvement. His eye and nerve involvement gradually improved over 20 months. It is feasible that IFN therapy has been a trigger for sarcoidosis in these patients.

Sarcoidosis and systemic vasculitis

Background: Systemic vasculitis is an unusual complication of sarcoidosis. Over a 10-year period, the authors have provided care for six patients who had features of both sarcoidosis and vasculitis. Vasculitis could not be attributed to other causes. Objectives: To report six patients (five children) who had sarcoidosis and systemic vasculitis and compare our experience with previous literature. To better delineate the clinical spectrum of sarcoid vasculitis and its response to therapy. Methods: Retrospective analysis and a Medline literature review of sarcoid and concurrent vasculitis from 1966. Results: Our six patients had systemic illnesses that included fever, peripheral adenopathy, hilar adenopathy, rash, pulmonary parenchymal disease, musculoskeletal symptoms, and scleritis or iridocyclitis. Biopsies revealed features compatible with the diagnosis of sarcoidosis or necrotizing sarcoid granulomata in either skin, lymph node, lung, synovium, bone, bone marrow, liver, trachea, or sclera. Arteriography showed features of large vessel vasculitis in three patients, all of whom were African American, whereas patients with small vessel vasculitis were white. Prior reports of sarcoid and vasculitis included 14 adults, of whom half had predominantly small vessel disease, and half had medium- or large-sized vessel disease. Eight previously reported children included seven with primarily large vessel sarcoid vasculitis. Racial background was noted in 15 reported cases and included whites (6), African Americans (5), and Asians (4). Among the authors' six patients, four improved when treated with prednisone alone. However, relapses occurred when the drug was tapered or withdrawn. Conclusions: Sarcoidosis may be complicated by systemic vasculitis that can affect small- to large-caliber vessels. Sarcoid vasculitis can mimic hypersensitivity vasculitis, polyarteritis nodosa, microscopic polyangiitis, or Takayasu's arteritis. African American and Asian patients are disproportionately represented among cases with large vessel involvement. Corticosteroid and cytotoxic therapy is palliative for all forms of sarcoid vasculitis. However, relapses and morbidity from disease and treatment is common. Semin Arthritis Rheum 30:33-46 Copyright © 2000 by W.B. Saunders Company

Cerebral germinoma with marked granulomatous inflammation: Granulomatous germinoma

Cerebral germinomas with granulomatous inflammation are rare lesions that can present diagnostic difficulties. Four cases (two male and two female) of germinomas with pronounced inflammatory reaction are presented. The age ranged from 14 to 21 years (mean 18). Three patients with vision defects had masses around the sellar region, and a long duration of symptoms (2, 4 and 5 years). The fourth patient had a mass in the temporal lobe; she had convulsions and the duration of her symptoms was short (3 weeks). All lesions consisted of inflammatory changes with scattered neoplastic germinoma cells that expressed placental alkaline phosphatase. The inflammation area occupied more than two‐thirds of the mass, and consisted of macrophages and their syncytial forms of mutinucleated giant cells, T‐cells, B‐cells, plasma cells, fibroblasts, and histiocytes or glial cells. Sarcoid granulomata were frequently seen, and multinucleated giant cells with Schaumann's bodies were also visible. The term ‘cerebral granulomatous germinoma’ is proposed for these unusual tumors. Moreover, it is likely that the study of cerebral granulomatous germinoma may provide some important clues towards the understanding of granulomatous inflammation in organs in general.

Recurrence of Sarcoidosis in Pulmonary Allograft Recipients

Lung transplantation is a potentially curative therapy for the end-stage pulmonary sequelae of sarcoidosis. We reviewed the course of five lung allograft recipients with underlying sarcoidosis (S) at the University of Pittsburgh Medical Center and compared them with a control group (C) of 44 contemporaneous transplant recipients with other respiratory diseases. Sarcoid granulomata have developed in the allografts of 4 S, although these lesions have not yet been demonstrated to result in clinically significant abnormalities. In comparison with C, sarcoidosis patients had significantly greater mean grades of acute rejection during the first 3 months after transplantation (2.1 +/- 0.3 versus 1.6 +/- 0.1, S and C, respectively, p < 0.042) and larger proportions of lung biopsies showing more than mild acute rejection (40 versus 18%, p < 0.012) and lymphocytic bronchitis (30 versus 13%, p = 0.02), as well as a greater percentage of polymorphonuclear leukocytes in BAL returns (34.9 +/- 5.4 versus 19.0 +/- 1.6, p < 0.01). The two groups did not differ, however, in frequency of obliterative bronchiolitis, survival, or pulmonary function. We conclude that lung transplant recipients with underlying sarcoidosis are very likely to develop recurrent disease in the allograft and have more severe acute rejection responses, especially in the first weeks after transplantation. Pulmonary transplantation appears to be an efficacious therapy for end-stage sarcoidosis, but the long-term sequelae of the increased acute rejection and recurrent sarcoidosis in the allograft remain to be determined.

Anticarbohydrate autoantibodies to sialidase-treated erythrocytes and thymocytes in serum from patients with pulmonary sarcoidosis

purpose: The presence of immunoglobulins and complement in sarcoid granulomata and bronchoalveolar lavage from patients with sarcoidosis suggests that humoral mechanisms may be of importance in granuloma formation. To test this hypothesis, we examined the possibility that antibodies to specific tissue carbohydrates causing alterations and/or dysfunction of immunocompetent cells might be present during sarcoidosis. Because we had previously shown the presence of sialidase activity in bronchoalveolar lavage from these patients, we have looked for the presence of antibodies that recognize sialidase-treated erythrocytes (mostly antigalactose) in the serum of patients with sarcoidosis. Since thymocytes are spontaneously recognized by peanut agglutinin, a lectin that binds galactose, the reactivity of serum from sarcoidosis patients with normal or neuraminidase-treated thymocytes has also been studied. patients and methods: Serum samples were obtained from the venous blood of patients with biopsy-proven sarcoidosis, most of whom had no extrathoracic symptoms. The mean patient age was 31 years, with a range from 21 to 57 years. There were 12 women and 19 men, and 10% of the patients were smokers. Sarcoidosis was classified as recent if symptoms had been present for less than 1 year and chronic if symptoms had been present for longer than this. Control serum samples were obtained from patients with idiopathic pulmonary fibrosis (n = 9) and from healthy volunteers (n = 15). Furthermore, serum from patients who had previously had sarcoidosis but in whom cures had been achieved was also studied (n = 6). results: Sialidase-treated erythrocytes were lysed in autologous serum upon incubation at 37°C providing that the serum came from a patient with active disease. Serum from either normal volunteers or patients with resolved sarcoidosis had no significant cytotoxic activity. Lysis proceeded through activation of the classical complement pathway following fixation of autoantibodies. These antibodies were predominantly of the IgM class. They were able to agglutinate neuraminidase-treated thymocytes, whereas untreated thymocytes did not fix the antibodies. Carbohydrate inhibition experiments demonstrated that these antibodies are mostly galactose specific. As this sugar is located immediately below the sialic acid residues in the carbohydrate moiety of membrane glycoconjugates, it is unmasked following sialidase treatment. conclusion: Since galactose has been shown to be present on the membrane of certain subsets of immunocompetent cells (e.g., lymphocytes and macrophages either spontaneously or after stimulation), it is possible that antigalactose antibodies may affect the metabolism of these cells, leading to some of the immune dysfunctions that are observed during sarcoidosis.

Immunopathology of ocular sarcoidosis

Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.

In vitro Autoradiographic Localization of Angiotensin-Converting Enzyme in Sarcoid Lymph Nodes

Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, 125I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosis had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p less than 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p less than 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p less than 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantitation of results, and autoradiographs may be stored indefinitely for later comparison.

Labial minor salivary gland biopsy: a highly discriminatory diagnostic method between sarcoidosis and Sjögren's syndrome.

Sixty labial minor salivary gland biopsies (lip biopsies) from 32 patients with sarcoidosis and 28 patients with primary Sjögren's syndrome were evaluated retrospectively and blindly. Six biopsies revealed typical sarcoid granulomata. All six belonged to patients with previously diagnosed sarcoidosis. Twelve lip biopsies, all from sarcoidosis patients, were classified as presenting 1+ or less lymphoid infiltrates according to Tarpley's classification. The biopsies of the remaining 14 patients with sarcoidosis showed normal tissues. Finally, 28 biopsies were classified as having 2+ or 3+ lymphoid infiltrates and/or fibrosis. All belonged to patients with Sjögren's syndrome. Our results indicate that lip biopsy has a rather low diagnostic yield in sarcoidosis (19%) but, more importantly, it can discriminate very well between sarcoidosis and Sjögren's syndrome.

Chronic sarcoid synovitis in the Caucasian: an arthroscopic and histological study.

Chronic synovitis is a rare complication of sarcoidosis, virtually confined to the black population. Synovial histology may be nonspecific or show typical sarcoid granulomata. We report 2 cases of chronic sarcoid synovitis in Caucasians. Histology showed typical granulomata in one patient, whose distinctive arthroscopic appearance is discussed.

Serum prolactin levels in eighty patients with sarcoidosis

Serum prolactin levels were measured by radioimmunoassay in eighty patients (thirty-four males, forty-six females) with sarcoidosis before treatment. In twelve patients (15%) serum prolactin levels were more than two standard deviations above the mean of normal subjects. Hyperprolactinaemia was found most frequently (22%) in patients with radiological stage II; however, 14% of patients with stage I also had elevated serum prolactin levels. In most cases serum prolactin levels fell to within the normal range after treatment with corticosteroid in parallel with improvement of intrathoracic lesions. These findings suggest that hyperprolactinaemia may be due to hypothalamic involvement by sarcoid granulomata. We conclude that the measurement of basal serum prolactin levels using radioimmunoassay is a sensitive and practical method for screening patients with sarcoidosis for hypothalmic lesions.

Elevation of Serum Angiotensin-Converting Enzyme in Gaucher's Disease

MEASUREMENT of serum angiotensin-converting enzyme has been found useful for confirming a diagnosis of active sarcoidosis.1 The mean serum level in patients with active sarcoidosis is twice that found in healthy controls or in patients with other types of chronic lung or granulomatous disease. Elevations of this serum enzyme activity are believed to result from the release or loss of the enzyme from epithelioid cells of the sarcoid granulomata.2 The serum level returns to normal in sarcoidosis with either spontaneous resolution of the disease or with therapeutic doses of corticosteroid medication. Thus, the elevated enzyme levels are not due to . . .

Massive splenomegaly, pancytopenia and haemolytic anaemia in sarcoidosis.

A 53-year-old dock labourer, presented with massive splenomegaly and subsequently developed pancytopenia. Complete haematoglogical remission was observed following splenectomy. Histological examination of the liver and spleen revealed sarcoid granulomata. A year after splenectomy, he died in an acute haemolytic crisis, a very rare complication of sarcoidosis. Evidence of generalized sarcoidosis was found at autopsy. The literature on haematological complications in sarcoidosis is reviewed.

Tuberculous meningitis as a complication of sarcoidosis.

In two patients with well established sarcoidosis, the acute onset of meningitis proved to be due to tuberculosis rather than to an extension of sarcoid granulomata to the meninges. The cerebrospinal fluid changes are very similar, and the differential diagnosis rests on a search for Mycobacterium tuberculosis.

The "wheat-stubble sarcoid granuloma": a new epithelioid granuloma of the skin.

Summary.— The introduction into the skin of chemical substances or organic matter can produce granulomata of sarcoid type. A new granuloma of this type related to wounds produced by the stubble of wheat is described. The diagnosis of this lesion is easy, taking into consideration its localization in the lower limbs, the wounds caused by stubble, and the identification of intracellular plant material in the granuloma. A host factor of probable immunological nature is suggested. There is a similarity between these sarcoid granulomata of the skin and some epithelioid granulomatous lesions of the lung due to the inhalation of chemical substances and organic matter, known as “extrinsic allergic alveolitis”.

Hyperprolactinemia in sarcoidosis.

Serum prolactin levels were measured in 34 patients with extrapulmonary sarcoidosis (10 men, 24 women). Four patients had the syndrome of galactorrhea and amenorrhea. Eleven patients (3 men, 8 women) had elevated serum prolactin levels, with values ranging between 5 and 100 ng/ml. Serum prolactin levels in age-matched healthy controls and in patients with tuberculosis were less than 2 ng/ml in all cases. In three of the four patients with the galactorrhea-amenorrhea syndrome, treatment with L-dopa suppressed prolactin secretion, with cessation of galactorrhea and increased gonadotropin secretion with resumption of menses. A subsequent autopsy examination of 1 male patient with hyperprolactinemia showed sarcoid granulomata in hypothalamic nuclei, bilaterally. In six of these patients the elevated serum prolactin concentration was the only endocrine abnormality detected. These studies suggest that sarcoid granulomata may selectively destroy specific hypothalamic nuclei that normally inhibit the secretion of prolactin by the anterior pituitary. Measurement of the serum prolactin concentration may serve as a sensitive test for the detection of hypothalamic involvement in some patients with sarcoidosis.