Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment.

Arsenal of pattern-recognition receptors alongside antibody production machinery make B cells vulnerable to autoimmune response if an autoantigen elicits both pathways in a self-sustained fashion. Systemic lupus erythematosus is an autoimmune disease characterized by autoantibodies to DNA, RNA and related structures. Murine studies demonstrated autoreactive B cell activation upon TLR9 stimulation with DNA-containing immune complexes. This activation could be abolished with chloroquine, a drug used in SLE treatment that also blocks TLR9 signaling. We investigated whether chloroquine modulates TLR9 expression, circulating DNA levels and B cell-related cytokines in newly discovered, untreated SLE patients. TLR9 was measured in peripheral blood B cells by flow cytometry, serum DNA by real-time PCR, and IL-10 and BAFF by ELISA before treatment, after 3weeks on corticosteroids, and 3months after introduction of chloroquine. We found that circulating DNA is higher in SLE patients than in controls in every time-point and decreases significantly after chloroquine treatment. Untreated patients had higher serum IL-10 than controls or patients on corticosteroids. Also, corticosteroids decreased and chloroquine completely abolished CpG-mediated CD86 upregulation on B cells and IL-10 secretion in PBMC culture. Providing the TLR9 pathway activation demonstrates its importance in pathogenesis of human SLE, this data supports continuation of chloroquine in SLE treatment protocol. In addition, observed modulation of cytokine and DNA levels after immunomodulatory treatment prompts for inclusion of untreated patients in studies of human immune disorders.

Low back pain as the presenting sign in a patient with primary extradural melanoma of the thoracic spine--a metastatic disease 17 years after complete surgical resection.

Primary spinal melanomas are extremely rare lesions. In 1906, Hirschberg reported the first primary spinal melanoma, and since then only 40 new cases have been reported. A 47-year-old man was admitted suffering from low back pain, fatigue and loss of body weight persisting for three months. He had a 17-year-old history of an operated primary spinal melanoma from T7-T9, which had remained stable for these 17 years. Routine laboratory findings and clinical symptoms aroused suspicion of a metastatic disease. Multislice computed tomography and magnetic resonance imaging revealed stage-IV melanoma with thoracic, abdominal and skeletal metastases without the recurrence of the primary process. Transiliac crest core bone biopsy confirmed the diagnosis of metastatic melanoma. It is important to know that in all cases of back ore skeletal pain and unexplained weight loss, malignancy must always be considered in the differential diagnosis, especially in the subjects with a positive medical history. Patients who have back, skeletal, or joint pain that is unresponsive to a few weeks of conservative treatment or have known risk factors with or without serious etiology, are candidates for imaging studies. The present case demonstrates that complete surgical resection alone may result in a favourable outcome, but regular medical follow-up for an extended period, with the purpose of an early detection of a metastatic disease, is highly recommended.

Propylthiouracil-induced anti-neutrophil cytoplasmic antibodies (ANCA) skin vasculitis: the first case reported in Croatia.

Drug-induced vasculitis is a known side effect of prolonged treatment with several drugs. It is characterized by inflammation and cellular infiltration of small vessels and presence of anti-neutrophil cytoplasmic antibodies (ANCA). Propylthiouracil and hydralazine (anti-thyroid and antihypertensive drugs) are the drugs most commonly associated with drug-induced vasculitis. Small vessels of the skin are most frequently affected, while affection of the vessels of the kidneys, central nervous system and lungs make the diagnosis life-threatening. When drug-induced vasculitis is suspected, quick and punctual diagnostic procedure should be carried out to exclude systemic manifestations. Treatment comprises of elimination of the causative drug, which is sufficient in most cases, but sometimes oral or parenteral glucocorticoids and even immunosuppressants are indicated. A case is presented of an 18-year-old male with a history of Graves disease treated with standard dose of propylthiouracil. Approximately 2.5 years after starting therapy he noticed formation of shallow skin ulcerations on both of his ear lobes and elbows. Detailed hospital work-up found high titers of perinuclear-staining anti-neutrophil cytoplasmic antibodies/myeloperoxidase (pANCA/MPO, 1:1024). Biopsy of the affected skin revealed leukocytoclastic vasculitis. Additional tests excluded systemic vasculitis. The patient was diagnosed with propylthiouracil-induced vasculitis, a form of drug-induced vasculitis. Propylthiouracil was discontinued and the skin lesions disappeared over time without the need of any specific therapy (such as glucocorticoids).

Rare zoonosis (hemotrophic mycoplasma infection) in a newly diagnosed systemic lupus erythematosus patient followed by a Nocardia asteroides pneumonia.

Systemic lupus erythematosus (SLE) is per se a disease characterized by suppressed immune response and thus susceptibility to various opportunistic infections. We describe the case of a 21-year old woman who developed a rare zoonosis - hemotrophic mycoplasma infection in the initial stage of SLE, complicated with Nocardia asteroides pneumonia afterwards. Nocardia infection coincided with initiation of glucocorticoids and cyclophosphamide therapy for SLE. After the treatment she recovered completely. To our knowledge the only case of human hemoplasmosis (then referred to as eperythrozoonosis) in medical literature was the one described by a group of Croatian authors 22 years ago. No cases of a hemotrophic mycoplasma infection in a SLE patient have been published up to now.

Rare zoonosis (hemotrophic mycoplasma infection) in a newly diagnosed systemic lupus erythematosus patient followed by a Nocardia asteroides pneumonia

Systemic lupus erythematosus (SLE) is per se a disease characterized by suppressed immune response and thus susceptibility to various opportunistic infections. We describe the case of a 21-yearold woman who developed a rare zoonosis - hemotrophic mycoplasma infection in the initial stage of SLE, complicated with Nocardia asteroides pneumonia afterwards. Nocardia infection coincided with initiation of glucocorticoids and cyclophosphamide therapy for SLE. After the treatment she recovered completely. To our knowledge the only case of human hemoplasmosis (then referred to as eperythrozoonosis) in medical literature was the one described by a group of Croatian authors 22 years ago. No cases of a hemotrophic mycoplasma infection in a SLE patient have been published up to now.

[Polymyalgia rheumatica]. / Reumatska polimialgija.

The etiology, pathogenesis, epidemiology, clinical picture, diagnosis, differential diagnosis and treatment of polymyalgia reumatica are presented.

Non-MS autoimmune demyelination.

Connective tissue diseases can be characterised by central nervous system (CNS) involvement, in some patients manifested by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from multiple sclerosis (MS) and other demyelinating processes, such as transverse myelitis and optic neuritis. Demyelinating process may be the feature of nervous impairment in systemic lupus erythematosus, Behcet's disease (BD), Sjoegren's syndrome (SS), systemic sclerosis (SSc) or very rarely other systemic autoimmune diseases. An acute isolated neurological syndrome, as the most common symptom of MS can sometimes be the only feature or even first manifestation of nervous impairment in connective tissue disease, hence presenting the diagnostic problem. Although the white matter abnormalities seen by magnetic resonance imaging may be similar in non-MS autoimmune demyelination and MS, it is the most important diagnostic tool in the differential diagnosis of the mentioned conditions. Investigating the presence of various autoantibodies potentially involved in the pathogenesis of demyelinating lesions as well as cerebrospinal fluid (CSF) analysis can be helpful.

[Cryptococcal meningitis as a diagnostic problem in a patient with SLE--case report]. / Kriptokokni meningitis kao dijagnosticki problem u bolesnika sa sustavnim eritemskim lupusom- prikaz bolesnika.

Systemic erythematosus lupus (SLE) is a disease with wide range of clinical manifestations, signs and symptoms. Disease outcome depends mostly on the affection of kidneys and central nervous system by the disease. Very important cause of death in patients with SLE is infection. Infections are very common among these patients due to aggressive immunosuppressive treatment that is needed for the disease inflammatory activity control. In this case report we have presented a patient with SLE who initially had severe renal affection, but also complications of immunosuppressive therapy that was administered. Even though the disease was accidentally diagnosed, it had a severe clinical progress. Because of lupus nephropathy, in the early phase of the disease we administered aggressive immunosuppressive therapy (combined parenteral therapy of glucocorticoides and cyclophosphamide). As an outcome of the combined effect of disease and immunosuppressive agents used in the treatment of the disease, the patient had increased infective diathesis (repeated infections caused by S. enteritidis--urinary infections and sepsis). During one of the disease flares the patient was hospitalized an opportunistic infection developed. It was meningitis caused by C. neoformans. This opportunistic mycosis infection presented with clinically totally nonspecific signs and symptoms of CNS affection. Therefore, we suspected affection of CNS with SLE. Even though all diagnostic procedures were made on time and that adequate antifungal and supportive agents were applied very early after the infection onset, the outcome was fatal. Because of infective diathesis in patients with SLE, which present with common and opportunistic infections, and due to high mortality rates caused by these infections, we have tried to emphasise the importance of taking adequate specimens early after infection outcome for these rare infective agents like C. neophormans. In recent medical literature are dominant cases reported in Asia. Reports from Europe are very rare, and this case is the one of that kind in Croatia.

[Surgical treatment of ophthalmologic complications in Behcet's disease]. / Kirurske mogucnosti lijecenja oftalmoloskih komplikacija Behçetove bolesti.

Behcet's syndrome is a chronic multisystem disease with recurrent oral and genital ulcerations and recurrent, usually bilateral uveitis. A 31-year-old female patient with uveitis who underwent vitrectomy is presented.

[Myopathy with rhabdomyolysis as an adverse effect of simultaneous treatment with cerivastatin and gemfibrozil]. / Miopatija s rabdomiolizom kao nuspojava istodobnog lijecenja cerivastatinom i gemfibrozilom.

Drug-induced myopathy and/or rhabdomyolysis have been reported with use of some statins and fibric acid derivatives. The risk of adverse effects is increased with their concomitant use. We report the case of myopathy with rhabdomyolysis during the concomitant use of cerivastatin and gemfibrozil.