Successful Desensitization to Sorafenib and Imatinib-A Report of Two Cases and a Literature Review.

BACKGROUND: Drug desensitization allows for safe administration of a drug to a patient with a previous hypersensitivity reaction. Successful desensitization protocols have been described for different medications, including protocols for oncology patients. Few cases of desensitization to sorafenib and imatinib have been described in the literature so far. OBJECTIVE: The objective of this paper is to describe the process of the sorafenib and imatinib drug hypersensitivity diagnosis and desensitization process in two patients. METHODS: Two oncology patients who experienced non-immediate hypersensitivity reactions to sorafenib and imatinib underwent desensitization to these drugs. We designed a protocol for the first patient and used a modified protocol from the literature for the second patient. RESULTS: By using a slow desensitization technique and gradual tapering of corticosteroids and antihistamines, both patients reached the target dose of the incriminated drug. CONCLUSIONS: Desensitization to sorafenib and imatinib can be an effective therapeutic option in patients with hypersensitivity to those medications, without alternative treatment options.

Early diagnosis of asymptomatic neurocutaneous melanosis (60 month follow-up).

Neurocutaneous melanosis (NCM) is a rare, sporadic, congenital neuroectodermal dysplasia. Large congenital melanocytic nevi (CMN) can evolve in a certain percentage of patients to NCM. Meningeal deposits are benign, but can be prone to malignant transformation in some cases. We describe the case of an infant with asymptomatic NCM, and typical magnetic resonance imaging (MRI) findings. The diagnosis was established shortly after delivery, and the patient was followed for 60 months. At that time, the girl did not have any neurologic symptoms; she reached normal developmental milestones and did not show mental retardation and did not develop malignant melanoma; further follow-up will be needed, although there are no reliable guidelines as to the time range of follow up of asymptomatic NCM in the literature. We report the typical MRI signal abnormalities of the brain, and present a review of the literature regarding this rare and mysterious congenital disorder.

[Importance of dysphagia examination in patient with dermatomyositis--case report].

INTRODUCTION: Polymiositis belongs to the group of inflammatory myopathies which are manifested by muscle weakness of the shoulder blade and pelvic region. The presence of typical skin manifestations is suggestive of dermatomyositis. These patients may also develop dysphagia (10-54%) as a result of involvement of the oropharyngeal and upper oesophageal striated muscles. Dermatomyositis may also be associated with another systemic disease or malignancy. CASE REPORT: Hereby is presented the case of a 42-year-old female patient hospitalized at the Department of Allergy and Immunology, Clinical Center of Serbia for the shoulder blade and pelvic muscle weakness and pains in the small and large joints, eyelid edema, facial and neckline redness, difficult swallowing and loss of body mass. Based on the presence of proximal muscle weakness, increased enzyme serum levels (lactic acid dehydrogenase, glutamic-oxalacetic transaminase), positive electroneuromyography findings, typical skin changes and positive muscle biopsy, the patient was diagnosed to have dermatomyositis. Both radioscopy and esophagography revealed some disturbances in all phases of swallowing, absence of all primary and secondary peristaltic waves accompanied by contrast medium aspiration. Additionally, esophageal manometry proved the absence of esophageal peristalsis. Additional examinations ruled out the presence of any malignancies. The patient underwent glycocorticoid and azatioprim treatment along with specific dietary regimen, symptomatic and physical therapy, which led to favorable clinical outcome. CONCLUSION: Dermatomyositis-associated dysphagia may lead to severe complications such as cachexia and aspiration pneumonia. In addition to the management of underlying disease, the treatment includes special dietary regimen, rehabilitation and even interventional surgical procedures, if necessary.

[Laboratory and morphologic parameters in patients with lupus nephritis]. / Laboratorijski i morfoloski parametri kod bolesnika s lupusnim nefritisom.

INTRODUCTION: Lupus nephritis is an example of glomerulonephritis mediated by immune complexes. The information obtained by kidney biopsy corroborates diagnosis and evaluation of disease activity, specify of prognosis and mode of treatment. The object of our study was to determine the prevalence of particular pathohistological types of lupus nephritis in our group of patients, to establish if there was a correlation of laboratory and morphological parameters, and to present the use of specific therapeutical protocols. METHOD: The study included 58 patients with diagnosed systemic lupus erythematosus (SLE) and lupus nephritis, who had biopsy of kidneys. The indications for biopsy were the following: proteinuria level over 0.5 g/24 hrs, erythrocyturia and cylindruria. The patients were examined and treated at the Institute of Allergology and Immunology, Clinical Centre in Belgrade, over the period 1994-2001. Within the testing, besides standard laboratory tests, the immunological evaluation was also performed as follows: the level of standard serum immunoglobulins, C3 and C4 components of complement, antinuclear antibodies (ANA) and antibodies to double-stranded DNA (dsDNA), were determined. RESULTS: There was 84.48% of female patients in the studied group. The mean-age was 36.5 years, while the average duration of disease (SLE) to kidney biopsy was 28.3 months. Considering cytopenia, leukopenia was found in 26.79% of patients, lymphopenia was recorded in 62.26% of cases while anaemia was noted in 52.63% of patients. The values of serum creatinine were elevated in 25.86% of patients, while creatinine clearance rate was lower (below 80 ml/min) in 75% of cases. The values of proteinuria are illustrated in Graph I. Cylindruria was found in 20.69% of subjects, massive erythrocyturia in 44.83%, and 46.55% of patients had more than 5 red blood cells in urinary sediment. Regarding the pathohistological findings, according to WHO classification, the biopsy of kidneys revealed the following distribution: class I--3.45% of patients, class IIA--24.14%, class IIB--31.03%, class III--12.07%, class IV--24.14%, class V--3.35%, and class VI 1.72% of cases. DISCUSSION: Within the immunological evaluation, the increased serum immunoglobulin G (IgG) level was found in 26.79% of subjects, suggesting that the consumption of complements in formation of immune complexes was the basic pathogenetic mechanism of lupus nephritis. Positive finding of ANA was recorded in about 95% of subjects, what was typical for SLE, while antibodies to dsDNA were positive in no less than 72.72% of cases, arguing for the fact that they were one of major nephritogenic antibodies. Considering the correlation analysis, no correlation between pathohistological findings and serum creatinine level was found, but there was the correlation between pathohistological findings and decreased creatinine clearance rate. The correlation between pathohistological findings and proteinuria up to 0.5 g/24 hrs was verified. There was no correlation between the increased IgG level and kidney biopsy findings, but it was found that decreased level of C4 complement component correlated with the degree of kidney lesion. The value of diastolic pressure also correlated with pathohistological findings. Concerning the applied mode of treatment, 46.55% of patients were administered pulse doses of cyclophosphamide combined with pulse doses of methylprednisolone, 5.17% had pulse doses of cyclophosphamide and 32.76% pulse doses of methylprednisolone, while 12.07% received glucocorticoid drugs combined with azathioprine, and glucocorticoids only were given to 3.45% of them. The conclusion will be that the biopsy of kidneys is the imperative in the evaluation of lupus nephritis, because the complete insight into the degree and type of kidney lesion as well as search for an optimal mode of treatment may be achieved only by assessment of combined clinical, laboratory and morphological parameters.