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.     

Abducens nerve palsy and Horner syndrome due to metastatic tumor in the cavernous sinus

A 41-year-old man was diagnosed as having primary parotid carcinoma on the right side. After radical parotidectomy, radiation therapy and systemic chemotherapy, the primary parotid carcinoma was completely remitted. Two years later, right abducens nerve palsy and Horner syndrome appeared. Neuroimaging demonstrated a gadolinium-enhanced lesion in the posterior portion of the right cavernous sinus, and metastasis of parotid carcinoma was suspected. After radiosurgery and systemic chemotherapy, the intracavernous lesion disappeared. This is the first case of combination of abducens nerve palsy and ipsilateral Horner syndrome due to metastasis from parotid carcinoma to the cavernous sinus.     

Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients

We conducted the current study to characterize the clinical presentation of primary Sj?gren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.     

Human immunodeficiency virus (HIV) and HIV infected cells in saliva and salivary glands of a patient with systemic lupus erythematosus.

A young woman with systemic lupus erythematosus (SLE) was infected with human immunodeficiency virus 1 (HIV-1) and about 6 years later developed persistent bilateral parotid gland enlargement. It was unclear whether this represented salivary gland involvement as a component of her SLE (secondary Sj?gren's syndrome) or the initial clinical manifestation of her HIV-1 infection. HIV proviral DNA was found in individual salivary glandular secretions and in whole saliva. Additionally, cells positive for HIV RNA were isolated from whole saliva. A parotid gland biopsy revealed infiltrating lymphocytes containing large amounts of HIV RNA.     

Immunoglobulin G4-related Disease Accompanied by Peripheral Neuropathy: A Report of Two Cases

Due to its rarity and the limited literature, the clinicopathological characteristics of peripheral nerve involvement in immunoglobulin G4 (IgG4)-related disease are unknown. We present two cases of IgG4-related disease, accompanied by peripheral neuropathy, presenting as unilateral ptosis (case 1) and sclerosing cholangitis (case 2), respectively. In both cases, sural nerve biopsy indicated vasculitis as the underlying pathophysiology; the peripheral neuropathy was refractory to corticosteroid therapy. In contrast to the previously proposed pathomechanism of IgG4-related neuropathy (direct lymphoplasmacytic infiltration), the pathological findings in our cases suggest that vasculitis occurs secondary to systemic autoimmune conditions.     

Multi-organ Involvement in Non-pulmonary Sarcoidosis

Isolated extrapulmonary involvement in sarcoidosis is uncommon and reported in 5–9% of systemic sarcoidosis, this constitutes a clinical challenge due to its extensive differential diagnosis. Extrapulmonary sarcoidosis affecting more than three organs is rarely reported and there are scarce literature data published on diagnosis, clinical course and management in those cases.We hereby discuss a case of a 41-year-old female with systemic non-pulmonary sarcoidosis affecting lacrimal gland, peripheral lymph nodes, parotid gland and the liver.     

Bilateral phrenic paralysis in a patient with systemic lupus erythematosus

Respiratory manifestations of systemic lupus erythematosus (SLE) are frequent. They include respiratory muscle abnormalities, which have been implicated in the pathogenesis of the "shrinking lung syndrome" (SLS). We report the case of a patient with this syndrome, in whom diaphragmatic paralysis due to demyelinating phrenic lesions was diagnosed at the same time as SLE. Follow-up studies showed a favorable clinical and diaphragmatic outcome with corticosteroid therapy, but little change in spirometry. It is concluded that severe diaphragm palsy is possibly due to phrenic nerve lesions in SLE, and that the link between diaphragm dysfunction and the SLS is probably not a straightforward one.     

Sarcoidosis occurring after interferon-alpha 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.     

Ear-nose-throat manifestations of autoimmune rheumatic diseases

Ear-nose-throat (ENT) manifestations of connective tissue disorders represent a diagnostic challenge for clinicians as they often constitute the initial sign of an otherwise asymptomatic autoimmune disease. Moreover, in patients with known autoimmune rheumatic diseases, ENT manifestations can be overlooked. Hearing disturbances may be seen in patients with systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis, polyarteritis nodosa, Cogan's syndrome, Sj?gren's syndrome, and less frequently in Churg-Strauss syndrome and Adamantiades-Beh?et's disease. Nose and paranasal sinuses are variably affected during the course of Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and sarcoidosis. Recurrent mucosal ulcerations are common in systemic lupus erythematosus and Adamantiades-Beh?et's disease. Xerostomia is a common feature of primary and secondary Sj?gren's syndrome; salivary gland enlargement may be also seen in these patients, as well as in patients with sarcoidosis. The cricoarytenoid joint can be involved during the course of rheumatoid arthritis, ankylosing spondylitis and gout; osteoarthritic changes have also been described. Motility disorders of the upper and/or the lower portions of the esophagus have been reported in patients with dermatomyositis/polymyositis, systemic sclerosis and systemic lupus erythematosus. Trigeminal nerve dysfunction may occur in patients with Sj?gren's syndrome, systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disease. Peripheral facial nerve palsy has been described to complicate the course of Sj?gren's syndrome and sarcoidosis.     

Sj?gren's syndrome in systemic lupus erythematosus

Sixty unselected consecutive patients with systemic lupus erythematosus (SLE) were prospectively evaluated for evidence of Sj?gren's syndrome. This was diagnosed in the patients whose minor labial salivary gland biopsy was graded greater than or equal to 3 (according to Chisolm and Mason), who also had keratoconjunctivitis sicca (positive rose bengal eye test) and/or xerostomia (subjective xerostomia and decreased stimulated parotid flow rate). Lip biopsy revealed focal round cell infiltration compatible with a greater than or equal to 3 grade in 11 patients, minimal perivascular infiltration in 21 patients and no infiltration in 28. In the positive biopsy group (greater than or equal to 3 grade) subjective xerophthalmia, decreased parotid flow rate, parotid gland enlargement, lymphadenopathy, presence of rheumatoid factor and anti-La (SSB) antibodies were significantly commoner than in the others. Of the 11 patients of this group, 5 had keratoconjunctivitis sicca which sufficed for the diagnosis of Sj?gren's syndrome, suggesting a prevalence of 8.3% in our population with SLE. In these individuals subjective xerophthalmia (40%), positive Schirmer's I eye test (60%), decreased parotid flow rate (80%), parotid gland enlargement (80%) and presence of rheumatoid factor (80%) and anti-La (SSB) antibodies (80%) were significantly more frequent than in the remaining patients, whereas significant differences regarding other features of SLE were not observed. Our results suggest that Sj?gren's syndrome in SLE is relatively rare and usually mild. Furthermore, it may present more similarities to primary Sj?gren's syndrome than to secondary Sj?gren's syndrome accompanying rheumatoid arthritis.     

Sialochemistry in human immunodeficiency virus associated salivary gland disease.

Human immunodeficiency virus (HIV) associated salivary gland disease is defined as the presence of enlargement of one or more major salivary glands and/or diminished salivary function in an HIV infected individual. It has a number of similarities to, as well as differences from, Sj?gren's syndrome (SS). We studied the sialochemistry of stimulated parotid saliva of 11 patients with HIV associated salivary gland disease and bilateral parotid gland enlargement, and compared these findings with those of 15 HIV negative controls, 13 HIV positive individuals with no salivary gland involvement and 18 individuals with SS. The patients with HIV associated salivary gland disease had a significant decrease in the level of salivary protein, with increases in salivary IgA, lysozyme and albumin compared to the HIV negative controls. There were no changes in concentration of electrolytes. The sialochemistry among the patients with HIV associated salivary gland disease was unrelated to the degree of immune suppression and did not change over a 6 month period. The observed changes were similar to those of SS but less pronounced. The similar clinical, histologic and sialochemical features of HIV associated salivary gland disease and SS suggest that these conditions share common pathogenetic mechanisms, which may be modified in the former by the HIV infection.     

Extrapulmonary presentation of sarcoidosis

Sarcoidosis is a systemic disease that usually has a pulmonary presentation. Extrapulmonary presentation of the disease is often unrecognized because the clinical signs ( eg, peripheral lymph nodes) and more important symptoms ( eg, renal stones or uveitis) do not usually indicate systemic disease. In three different long-term studies of patients with sarcoidosis, 1.5% of the patients presented with uveitis, 11.7% presented with peripheral lymph nodes, and 3.6% presented with renal stones; a total of 16.6% of the patients had extrapulmonary presentation of sarcoidosis. Two of the three studies were retrospective. Many patients may have skin, parotid gland, spleen, liver, central nervous system, bone, or heart presentation; 16.6% is only the tip of an iceberg. A well-conducted, prospective, long-term study could indicate that more than 30% of patients with sarcoidosis have extrapulmonary presentations of the disease.     

Acute pan-dysautonomia as well as central nervous system involvement and peripheral neuropathies in a patient with systemic lupus erythematosus

A 32-year-old woman was diagnosed with leucopenia in 2002, being antinuclear antibody, anti-DNA antibody, and antiphospholipid antibody positive, and she was administered low-dose aspirin. In July 2006, she was admitted to our hospital because of pyrexia and abdominal pain. Examination revealed paralytic ileus, absence of the pupillary light reflex, dyshidrosis and anuresis. In addition, with high-level interleukin-6 in cerebrospinal fluid, the sensory nerve conduction velocity was derivation impotence. She was subsequently diagnosed with systemic lupus erythematosus (SLE) with central nervous system involvement, peripheral neuropathy as well as acute pan-dysautonomia. After pulse corticosteroid therapy, paralytic ileus was improved, however, the urination disorder persisted, and syncope due to orthostatic hypotension became marked. Plasma exchange and a second course of pulse corticosteroid therapy were performed, and were ineffective, whereas intravenous cyclophosphamide was effective. This patient is a rare case of central nervous system, peripheral neuropathy as well as acute pan-dysautonomia with SLE.     

South American blastomycosis: ophthalmic and oculomotor nerve lesions

A case of South American blastomycosis began with an oropharyngeal lesion which was followed by a granulomatous uveitis. The patient was treated with Amphotericin B and showed a clinical regression. Four months later, he developed a right 3rd cranial nerve palsy, aggravating the clinical aspect with a severe generalized involvement of the central nervous system and death. Necropsy showed blastomycotic meningoencephalitis.     

Drug-induced hypersensitivity syndrome in internal medicine: diagnostic and therapeutic traps. Eight observations

PURPOSE: Drug-induced hypersensitivity syndrome (DIHS) is an acute and severe drug reaction. Manifestations include severe skin lesions, fever, nodal enlargement, blood eosinophilia and multisystemic involvement. The severe systemic manifestations of DIHS are responsible for a 10% mortality rate. The pertinence of corticosteroid therapy is discussed. METHODS: The authors report eight retrospective cases of DIHS obtained from the PMSI (Programme de Médicalisatiopn des Systèmes d'Information) between November 1991 and November 1998. RESULTS: The series consisted of five male and three female patients (mean age: 52.6 years; range: 23-83 years). The interval between the introduction of the drug and the onset of the reaction varied from two to eight weeks. Due to severe systemic manifestations, three patients were given corticosteroid therapy. Healing of skin and systemic disorders resolved with a mean delay of 4.4 weeks (range: 1 to 56 weeks). CONCLUSION: DIHS can be a diagnostic trap, as there are no diagnostic criteria for DIHS. Only the association of multiple arguments such as the time to the occurrence of symptoms, clinical similarity to many infectious illnesses, hypereosinophilia, atypical lymphocytosis, etc. may help guide diagnosis. DIHS can also be a therapeutic trap, as prompt withdrawal of the offending drug is essential to minimize morbidity. Although still controversial in the literature, the pertinence of corticosteroid therapy may be discussed in case of severe systemic effects. Patch testing can be a valuable tool to determine the responsibility of a drug; however it proves to be useful only when positive.     

Diffuse infiltrative lymphocytosis syndrome in human immunodeficiency virus infection--a Sj?gren's-like disease

Certain adults and children with human immunodeficiency virus (HIV) infection develop a syndrome characterized by marked parotid gland enlargement, sicca symptoms and pulmonary insufficiency. Lymphocytic tissue infiltration is accompanied by circulating CD8 lymphocytosis, and autoantibodies are infrequently observed. Progressive lymphocytic visceral involvement may necessitate the careful use of immunosuppressive therapy, in addition to antiretroviral agents. Specific associations with particular MHC class I and II gene products suggest that this disorder may represent a distinctive host immune response to HIV. Infection with HIV should be considered in all high-risk individuals presenting with the sicca syndrome. Similarly, it should be considered in individuals in whom Sj?gren's disease is a diagnostic possibility but where atypical features are present.     

Benign parotid enlargement in bulimia

Bulimia is an episodic compulsive urge to overeat often followed by recurrent attempts to lose weight by self-induced vomiting. Seven young women with this eating disorder and associated benign bilateral painless parotid enlargement are described. The glandular swelling was generally intermittent, with parotid enlargement usually developing 2 to 6 days after a binge overeating episode had stopped. Several had hypokalemic alkalosis and a moderate elevation in serum amylase levels. None had clinical evidence of pancreatitis, and a parotid gland biopsy in one patient was normal. The clinician should be alerted to the association of benign parotid enlargement with this syndrome.     

Primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is a relatively common autoimmune systemic rheumatic disease. In addition to sicca syndrome and swollen salivary glands, systemic features manifest in the majority of patients, and are severe in 15%, particularly affecting the joints, skin, lungs, and peripheral nervous system. A recent meta-analysis estimated a pooled relative risk of 13.76 for the development of non-Hodgkin lymphoma, particularly in pSS patients who have parotid enlargement, vasculitis, cryoglobulinemia, and antibodies to Ro and La. pSS is the underlying diagnosis in one-third of mothers of neonates affected by congenital heart block. The diagnosis of pSS is complex and requires a stepwise approach to evaluate symptoms of ocular and oral dryness, objective measures of lacrimal and salivary gland dysfunction, and evidence of autoimmunity with Ro/La autoantibodies and labial salivary gland biopsy. It is essential to eliminate other autoimmune diseases, as well as non-autoimmune causes of sicca syndrome, such as menopause, endocrine diseases, anticholinergic effects of drugs, and fibromyalgia, to delineate pSS patients who are at risk of systemic complications. Recent major advances in the diagnosis of pSS have been the development of classification criteria, which serve as a template for clinical diagnosis, and outcome measures for use in clinical trials and prospective patient cohorts. Clinical data and biological samples from longitudinal cohorts, embedded into clinical practice, will be essential to further improve the diagnosis and management of pSS, increase knowledge about the natural history of the disease, gain insights into its pathogenesis, and stratify patients according to their risk of systemic disease and NHL. At present, there is a gap in evidence regarding the role of structured protocols in the management of pSS. Recent recommendations for the management of sicca symptoms and clinical trials of disease-modifying therapy are discussed.     

The eye and inflammatory rheumatic diseases: The eye and rheumatoid arthritis,ankylosing spondylitis,psoriatic arthritis

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are associated with potentially sight-threatening inflammatory eye disease. Although the ocular manifestations associated with ankylosing spondylitis and psoriatic arthritis are similar, such as anterior uveitis, this differs from rheumatoid arthritis where dry eye, peripheral ulcerative keratitis and scleritis are the major ocular complications. Apart from causing sight loss, these conditions are painful, debilitating, often recurrent or chronic and may require long-term therapy. Treatments such as ocular lubricant, topical corticosteroid, systemic corticosteroid and systemic immunosuppression are often similar for the underlying systemic disease. Yet for the treatment of the ocular complications, the evidence base is weak. Close collaboration with a rheumatologist is often essential, particularly in the management of these patients.