Rare manifestations of sarcoidosis in modern era of new diagnostic tools.

BACKGROUND & OBJECTIVES: Growing body of literature on sarcoidosis in India has led to an increased awareness of the disease. With the advent of better imaging tools hitherto under-recognized manifestations of sarcoidosis are likely to be better recognized. We sought to study the rare clinical and radiological manifestations (<5%) in patients with sarcoidosis. METHODS: Retrospective review of records of 164 patients with histopathologically proven sarcoidosis seen over six years in a tertiary care centre in north India, was done. RESULTS: Fifty four rare manifestations were observed in 164 patients. Acute presentation in the form of Lofgren syndrome was seen in eight (4.9%) and Heerfordt's syndrome in two (1.2%) patients. Musculoskeletal manifestations included chronic sarcoid arthritis in three (1.8%), deforming arthritis and bone erosion in one (0.6%) each. Rare initial presentation with dilated cardiomyopathy in one (0.6%), complete heart block in two (1.2%), bilateral sequential facial nerve palsy in two (1.2%), and pyrexia of unknown origin was seen in one (0.6%) patient. Other rare manifestations included chronic respiratory failure in one (0.6%), dysphagia in one (0.6%), sicca syndrome in five (3%), massive splenomegaly in one (0.6%), portal hypertension in two (1.2%), hypersplenism, gastric sarcoidosis, ninth and tenth cranial nerve palsies, moderate pericardial effusion and nephrocalcinosis in one (0.6%) each, and pulmonary artery hypertension in two (1.2%) patients. Rare radiological manifestations included moderate pleural effusion in two (1.2%), pleural thickening in five (3%), calcification of intrathoracic lymph nodes in four (2.4%), alveolar (nodular) sarcoidosis in three (1.8%), and myocardial uptake of 18F-fluorodeoxyglucose (F-18 FDG) in two (1.2%) patients. Fourteen patients had airways obstruction and behaved typically like seasonal bronchial asthma with excellent response to corticosteroids. INTERPRETATION & CONCLUSIONS: Increased awareness of rare manifestations will facilitate better management of these patients. With increasing use of modern diagnostic tools, manifestations hitherto considered rare, are likely to be recognized more frequently in the future.

[Castleman's disease : a rare differential diagnosis for Heerfordt's syndrome]. / M. Castleman : Eine seltene Differenzialdiagnose zum Heerfordt-Syndrom.

A 50-year-old male patient demonstrated an existing left proptosis for several weeks. The patient was suffering from physical exhaustion and had lost considerable weight. Furthermore, we observed greatly enlarged parotid and submandibular glands on both sides. MRI of the neck showed multiple, sharply circumscribed lesions in the major salivary glands and both lacrimal glands as well as in the orbit. Initially we suspected Heerfordt's syndrome, a manifestation of sarcoidosis, but laboratory diagnosis could not reveal a pathological erythrocyte sedimentation rate or an increased ACE titer. After exploratory excision from the right submandibular gland, histological examination revealed Castleman's disease. Therefore, we initiated an immunomodulatory therapy with interleukin-6 receptor antagonists.Castleman's disease is one of the very rare, benign, lymphoproliferative processes that have a tendency to turn malignant. Isolated findings of Castleman's disease should be completely resected. There are no clear treatment strategies for multiple localizations of Castleman's disease. The approaches range from systemic glucocorticoid therapy with chemotherapy to immunomodulatory treatment. In contrast to isolated findings, the prognosis for multicentric occurrence is unfavorable.

Multisystemic sarcoidosis revealed by a Heerfordt syndrome: case report.

Heerfordt syndrome is a rare clinical form of sarcoidosis with a favorable evolutionary profile in the majority of cases. In its classical form, it associates uveitis, parotidomegaly, facial paralysis and fever. We report a case of multisystemic sarcoidosis type II revealed by a Heerfordt syndrome in a 51-year-old female patient.

HLA-DRB1* alleles and symptoms associated with Heerfordt's syndrome in sarcoidosis.

Heerfordt's syndrome (HS) consists in its complete form of uveitis, parotid or salivary gland enlargement and cranial nerve palsy. The objective of the present study was to analyse if there are also links between HLA-DRB1* alleles and HS, as it is a specific phenotype of sarcoidosis. 1,000 patients with sarcoidosis, out of whom 83 had symptoms associated with HS, were included in the study together with a group of 2,000 healthy individuals from the same population, matched for sex and age. HLA-DRB1* allelic groups were determined for all individuals, and comparisons were made between different disease subgroups and between patients and healthy controls. We found that the HLA-DRB1*04 allele was overrepresented in patients with symptoms associated with HS. 83 (8.3%) of all patients had one or more of the symptoms and 46 (55%) of them were HLA-DRB1*04 positive. 44 (55%) of the patients with ocular sarcoidosis, i.e. the most common symptom associated with HS, were HLA-DRB1*04 positive, compared with 35.9% of healthy controls (p=0.0008), and only 26.6% of the whole group of sarcoidosis patients (p<0.0001). HLA-DRB1*04 seems to protect against overall sarcoidosis but appears to be a significant risk factor for ocular sarcoidosis as well as for other manifestations associated with HS.

[Case of Heerfordt's syndrome presenting polyneuropathy].

BACKGROUND: Acute presentation of sarcoidosis with the combination of uveitis, parotid gland enlargement, facial nerve palsy, and fever is called Heerfordt's syndrome. Clinically recognizable involvement of the nervous system occurs in < 10% of patients with sarcoidosis, and polyneuropathy in 24% with neurosarcoidosis. CASE: A 28-year-old woman diagnosed with Guillain-Barré syndrome was admitted and treated for a month in the Department of Neurology, Mie University hospital. Her visual acuity decreased 2 weeks after discharge. She was admitted to the Department of Ophthalmology, Mie University Hospital. She presented typical optic sarcoidosis. As she had uveitis, facial nerve palsy, parotid gland enlargement and fever in the clinical course, we diagnosed her condition as Heerfordt's syndrome. CONCLUSION: On rare occasions a Heerfordt's syndrome patient may present with Guillain-Barré-like symptoms.

Heerfordt's Syndrome Associated with Trigeminal Nerve Palsy and Reversed Halo Sign.

Heerfordt's syndrome is a rare subtype of sarcoidosis and features a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever. Cases with two of three symptoms are called "incomplete Heerfordt's syndrome." Heerfordt's syndrome involving other cranial nerve symptoms is relatively rare. We herein report a case of incomplete Heerfordt's syndrome presenting with trigeminal nerve palsy and a reversed halo sign, a rare manifestation of pulmonary sarcoidosis. The histological diagnosis following a biopsy of the parotid gland and endobronchial ultrasound-guided trans-bronchial needle aspiration of the mediastinal lymph nodes was sarcoidosis. The symptoms and lung lesions improved after corticosteroid therapy.

[Heerfordt's syndrome: about a case and literature review]. / Syndrome de Heerfordt: à propos d'une observation et revue de la littérature.

Heerfordt's syndrome is a rare manifestation of sarcoidosis combining uveitis, parotidomegaly, facial paralysis and fever in its classic form. It is an active form of the disease whose diagnosis is facilitated by salivary gland biopsy. We conducted clinical observation of a 17-year-old female patient with uveitis, right parotidomegaly and right facial paralysis characterized by violent onset. After laboratory tests and imaging exam (parotid ultrasound), biopsy of minor salivary glands established the diagnosis of sarcoidosis. A pre-therapeutic assessment allowed for the initiation of oral corticosteroid therapy with favorable outcome and total remission. Heerfordt's syndrome is a rare clinical form of sarcoidosis, with favorable outcome in most cases. Specific diagnostic approach (excluding differential diagnoses, especially the incomplete forms) is necessary, based on therapeutic advances in this area.

Sarcoidosis (Heerfordt syndrome): a case report.

We report the case of a 22-year-old woman who is suspected of having primary Sjögren s syndrome. She complaining of bilateral swelling of eyelids and the parotid glands of three weeks duration. Physical examination revealed a bilateral enlargement of both parotid glands, which were solid and painful. Sjögren s syndrome was suspected at that stage, and the serologic and specific analysis were done. All these tests didn t find any autoimmune or visceral features typical of Sjögren s syndrome and autoantibodies were negative. During follow-up time the right facial nerve palsy developed. Pulmonary radiography revealed bihilar lymphadenopathy and labial salivary gland biopsy revealed non-caseating granuloma. The patient was classified as having stage I sarcoidosis. This case demonstrates the importance of being aware of the leading clinical signs and symptoms in case of Heerfordt syndrome.

Do you know this syndrome? Heerfordt-Waldenström syndrome.

Heerfordt-Waldenström syndrome is a rare subacute variant of sarcoidosis, characterized by enlargement of the parotid or salivary glands, facial nerve paralysis and anterior uveitis. Granulomas with a peripheral lymphocyte deficit are found in the anatomic pathology of affected organs. It is normally self-limiting, with cure achieved between 12 and 36 months, but some prolonged cases have been reported. Diagnosis of the syndrome is clinical, and treatment depends on the degree of systemic impairment. Oral corticosteroids represent the first line treatment option. The mortality rate ranges between 1 and 5% of cases.

[A case of Heerfordt's syndrome with an elevated serum TNF alpha].

A 27-year old man who had developed uveitis, swelling of the right parotid gland, right facial nerve paralysis and fever, was admitted to our hospital. A chest X-ray film showed bilateral hilar lymphadenopathy. Serum levels of angiotensin-converting enzyme and lysozyme were elevated. Histological findings of transbronchial lung biopsy specimens showed non-caseous epithelioid cell granulomas. Therefore, sarcoidosis was diagnosed. This case also fulfilled the criteria for Heerfordt's syndrome. Adiministration of prednisolone (PSL) initially improved the patient's symptoms, but rapid tapering of PSL worsened his symptoms. Thus, administration of high-dose PSL for a long time was required. He also showed elevated levels of TNF alpha in serum.

[Case of Heerfordt's syndrome with prolonged peripheral nerve involvement].

A 28-year-old man complaining of myiodesopsia was given a diagnosis of uveitis. Subsequently he complained facial nerve palsy and enlargement of parotid gland. Heerfordt's syndrome was diagnosed based on the results of several examinations. Facial nerve palsy, enlargement of the parotid gland and uveitis were improved by systemic corticosteroid therapy. At present he is receiving systemic corticosteroid therapy, but numbness in the mouth, thought to be the involvement of the trigeminal nerve, remains. Systemic corticosteroid therapy is usually effective for most cases with Heerford's syndrome. On the other hand, there are some cases with the prolonged peripheral nerve involvement despite systemic corticosteroid therapy, as seen in this case. If peripheral nerve involvement is prolonged, it is necessary to consider small-fibre neuropathy as one possible cause.

Differential diagnosis of facial nerve palsy.

Facial nerve palsy is the most frequent neurological presentation of sarcoidosis. It occurs with equal frequency on the right or left side, and equally unilateral or bilateral. When bilateral facial palsy develops in a young adult, sarcoidosis is the most likely cause. In our series of 147 patients with ocular sarcoidosis, facial palsy occurred in 12 per cent and parotid gland enlargement in 10 per cent. Resolution of facial palsy is complete in 80 per cent of patients. It does not recur, unlike orofacial granulomatosis in which facial palsy tends to be recurrent. The differential diagnosis is large (Table I) and needs full investigation in order to provide a better understanding of the treatment and prognosis. A 7-point scheme of management is set out for the patient with idiopathic facial nerve palsy.

Necrotizing sarcoid granulomatosis with and without extrapulmonary involvement.

Three cases of necrotizing sarcoid granulomatosis (NSG) are reported. All 3 patients had pulmonary lesions; one of them had additional extrapulmonary lesions which were ophthalmologic (dacryoadenitis) and digestive (ulcerative colitis). This patient was followed for 5 years and developed several respiratory, ophthalmologic and digestive recurrences. In 2 cases the diagnosis of NSG had been initially overlooked and the authors emphasize the difficulties of this histologic diagnosis in terms of the differential diagnosis with other necrotic and granulomatous pulmonary diseases such as tuberculosis and Wegener's granulomatosis. They stress the possibility of extrapulmonary lesions in NSG and discuss the relationship between NSG and sarcoidosis.

Salivary gland involvement in systemic diseases.

The salivary glands participate in systemic illnesses because they are secretory structures allied with the gastrointestinal tract. Thus they are involved in systemic inflammatory, allergic, and neoplastic conditions. Perhaps the most common condition is that of mumps in the acute phase. Of the chronic diseases, Mikulicz's disease or Sjögren's syndrome is most frequently noted. In most instances of systemic involvement, the salivary gland enlargement is the rule, with the gland being tense, soft, and enlarged, and with progressive growth over a period of time. Usually all glands are involved. The diagnosis should be suspected from the history and the physical examination, noting that all the glands are equally involved by the enlargement. If there is any question, a biopsy should be performed. In the case of Sjögren's syndrome, the biopsy specimen may be taken either from a major salivary gland or from one of the minor ones, or the nasal mucous membrane or oral cavity. In general, definitive therapy is unsuccessful for the systemic illness involving the salivary glands, and in most instances has to be supportive.

Heerfordt syndrome: a cause of facial paralysis.

Heerfordt syndrome is an unusual manifestation of systemic sarcoidosis and is characterized by parotitis, uveitis, and facial nerve paralysis. A case is presented and the clinical manifestations are discussed. Angiotensin converting enzyme assays along with tissue biopsy demonstrating noncaseating granulomas confirm the diagnosis.

[Heerfordt's syndrome remitting without corticosteroid therapy].

A 25-year-old woman presented with low-grade fever, uveitis, and bilateral swelling of the parotid glands. Her older sister had a history of sarcoidosis. A chest X-ray film showed bilateral hilar lymphadenopathy. The low-grade fever persisted after admission. Ga scintigraphy showed abnormal uptake in the parotid glands and hilar lymph nodes bilaterally. Sarcoidosis was diagnosed histologically after epithelioid cell granulomas without caseous necrosis were found in a specimen obtained by transbronchial biopsy. Heerfordt's syndrome was the final diagnosis. Six days after admission, left facial and left trigeminal nerve paralysis developed. The symptoms remitted without steroid therapy and, as of eight months after discharge there had been no evidence of recurrence.