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Dear Editor, Paraneoplastic dermatomyositis is a distinct clinical variant of dermatomyositis (DM) in which the typical cutaneous features and muscle weakness appear before, simultaneously, or after the diagnosis of an internal malignancy. It occurs in approximately one-third of patients with DM, predominantly adults, after the age of 40 (1). Different neoplasms have been described in association with DM, the most common of which are lung, breast, ovarian, gastrointestinal, prostate, and bladder cancers. The gender distribution of cancer type corresponds roughly to that of the general population (1,2). We report the case of a 58-year-old man who presented with facial heliotrope erythema, periorbital edema, Gottron's papules over the interphalangeal and metacarpophalangeal joints, and Gottron's sign on the elbows (Figure 1). The patient also exhibited some less frequent skin signs of DM, such as shawl sign on the upper back and shoulders and V-sign on the neck and chest. Apart from the rash, he complained of weight loss, adynamia, dysphagia, cough, and scant expectoration, which he reported experiencing over a 3-month period. The muscle involvement consisted of proximal muscle weakness and had appeared a month after the skin rash. The histology of the skin lesion revealed epidermal atrophy, vacuolar degeneration of the basal keratinocytes, and perivascular and periadnexal lymphocytic infiltrate in the upper dermis (Figure 2). Laboratory examination found increased creatine kinase (2822 U/L) and liver enzymes, anemia, and leukocytosis. Screening for antinuclear antibodies and anti-Jo1 autoantibodies were both negative. The diagnosis of trichinosis was excluded via serologic examination. The impaired general condition of the patient led to a prompt paraneoplastic screening. Abdominal sonography detected hepatomegaly. Computed tomography (CT) of the abdomen and pelvis visualized a mass in the distal part of the esophagus, narrowed lumen of the gastric cardia, enlarged gastric lymph nodes, lung and liver metastases, and ascites (Figure 3). The diagnosis of paraneoplastic DM in association with an advanced, metastatic, primary gastric carcinoma was established. Palliative surgery and chemotherapy were proposed to the patient, but he refused both. A systemic therapy with methylprednisolone 60 mg/daily and azathioprine 100 mg/daily was initiated, aiming to alleviate the progressively worsening muscle weakness, but proved ineffective. The patient died two months later of combined respiratory and heart failure. There are multiple prediction factors, such as cutaneous signs, laboratory data, and disease progression, which may direct the physician towards the possibility of paraneoplastic DM. Some atypical cutaneous lesions, such as cutaneous necrosis or vasculitis, hyperkeratotic follicular papules, vesiculo-bullous lesions, and flagellate erythema, are seen more frequently in cancer-associated DM (3,4). None of these were present in our patient. Pruritus is also described as a paraneoplastic sign (5). Some authors consider the increased erythrocyte sedimentation rate and C-reactive protein to be of predictive value for malignancy. Myositis-specific autoantibodies anti-TIF1-γ and anti-NXP-2, among the numerous novel serological markers for DM, are clearly associated with the presence of neoplasia (6,7). Unfortunately, we were unable to test for those autoantibodies. The symptom of dysphagia is a hallmark of paraneoplastic dermatomyositis and usually represents a manifestation of muscle weakness (8). In our case, it was rather a reflection of the endoluminal tumor, although it may also be a combination of both factors. In their study, Bowerman et al. investigated the risk of cancer development in different DM subtypes (9). They included 201 patients with adult-onset DM, 142 of with classic DM and 59 with the clinically amyopathic type. The estimated prevalence of malignancy-associated classic and clinically amyopathic DM were 9.9% and 1.7%, respectively. The authors concluded that older age and classic DM represent independent risk factors for malignancy-associated DM within 2 years of disease onset. Given that early diagnosis significantly impacts prognosis in patients with cancer-associated DM, recent studies support blind screening for internal malignancy (10). Leatham et al. performed a retrospective analysis of 400 patients with DM, finding a total of 53 cancers in 48 patients (some of the patients had two separate neoplasms). Among the group of paraneoplastic DM cases, 17 cancers were diagnosed via purely blind screening in patients with a lack of concerning history or physical examination. The authors claimed that the most informative tests were mammography and CT scanning. The above-mentioned predictive factors for paraneoplastic DM represent a useful tool for the clinician. Although it is generally accepted that patients with DM should undergo some type of cancer screening, there is no consensus regarding methods or frequency. New data suggest that blind screening in asymptomatic patients might be of great importance for early diagnosis and treatment of patients with cancer-associated DM.

Few patients with systemic lupus erythematosus have features of verrucous (hypertrophic) lupus erythematosus. A 29-year-old Caucasian woman with a 7-year history of systemic lupus erythematosus developed painful verrucous plaques on the nose. Erythematous, raised, indurated, hyperkeratotic plaques localized on the dorsa of the distal parts of the toes and over the interphalangeal joints of her fingers were also noted. A large, dull-red, indurated plaque with rolled borders on the bridge of the nose was most characteristic. Rapid therapeutic effect was obtained by systemic corticosteroid regimen. This verrucous variant of lupus erythematosus, sometimes clinically resembling actinic keratosis, keratoacanthoma and squamous cell carcinoma, is reviewed.

The induction of IL-12 and IL-10 production by the immunomodulatory C3 binding glycoprotein (C3bgp) was studied on human peripheral blood mononuclear cells (PBMC). Isolated PBMC from healthy human donors were cultured 24 hours with C3bgp isolated from Cuscuta europea. We studied also the influence of C3bgp on the cytokine production in LPS-, PHA- and PWM-stimulated PBMC. The levels of these cytokines in the various culture supernatants were subsequently determined using ELISA. Results showed that amount of IL-12 was significantly higher in C3bgp-stimulated cultures in comparison with LPS-, PHA- and PWM-stimulated PBMC. C3bgp also significantly increased IL-12 in PHA- or PWM-stimulated cultures, but not in LPS-stimulated culture. C3bgp alone was a weak inducer of IL-10 production, compared to the other stimuli. Furthermore it inhibited IL-10 production after LPS, PHA and PWM stimulation. Taken together these results indicate that immunomodulatory C3 binding glycoprotein has the ability to change IL-12/IL-10 ratio in stimulated human PBMC.

This study investigated the functionality of the -1082(A/G) polymorphism in the promoter of the IL10 gene and +16974 (A/C) SNP in 3'UTR of the IL-12B gene in association with the cytokine production from stimulated PBMC in relation with sepsis. A group of 33 patients in ICU and 99 healthy volunteers were included. The SNP in IL-12B gene was detected by restriction assay using Taq I enzyme. The amplification refractory mutation system PCR was used for IL-10 -1082(A/G) detection. The results for IL-10 - 1082 SNP demonstrated that AA genotype was associated with the lower IL-10 production in LPS- or PHA-stimulated PBMC. Carriage of at least one copy of IL-10 - 1082 allele G in sepsis patients as well as in healthy controls resulted in significant increase in IL-10 production from stimulated PBMC. Sepsis patients with AG/GG genotypes of IL-10 -1082 produced significantly higher IL-10 from stimulated PBMC. The presence of “C” allele in IL-12B gene correlated with strongly decreased production of IL-12p40 of stimulated PBMC from sepsis patients. In conclusion it was demonstrated that the induced production of IL-12 and IL-10 depended on polymorphisms in corresponding genes and physiological status.

Interleukin-12 (IL-12) is a 75-kDa heterodimer composed of two disulfide-linked subunits, designated p35 and p40, and encoded by separate genes on chromosomes 3p12-3q13.2 and 5q31-33 respectively. A complete genomic sequence analysis of the IL-12 gene encoding its p40 subunit identified several intronic polymorphisms and a Taq1 (A/C) single nucleotide polymorphism (SNP) in the 3'- untranslated region (UTR) at position +16974. The aim of our study, the first to be performed on Bulgarian citizens, was to determine the genotype and allelic frequencies of a Taq1 polymorphism in 3'-UTR of the IL-12 p40 gene in two ethnic groups – Bulgarians (n=58) and Turkish minority (n=33) – in Bulgaria. Genomic DNA was PCR amplified using primers that covered the Taq1 restriction site. The 1046-bp amplified fragment was cut with the Taq1 restriction enzyme. The 16974 C allele yielded restriction site for the enzyme. Our results showed that Bulgarians and Turkish minority in Bulgaria have no differences in genotype and allelic frequencies of SNP in the 3'-UTR of the IL-12 p40 gene. Genotype distribution in the group of Bulgarian citizens was: AA (61%), CA (32%) and CC (7%). The observed allelic frequency of “A” - 0.77 for Bulgarian citizens- was similar to frequencies reported for other Caucasian populations.

The dynamics and quantitative analysis of monospecific antibody during the primary and secondary humoral responses were determined in the inbred strain and outbred stocks of rabbits. The antibody response in rabbits immunized against keyhole limpet hemocyanin (KLH) was studied during a 4-month immunization period. By ELISA method we determined the quantities of total anti-KLH comprising IgG, IgM, IgA on one hand and IgG alone in preimmune and immune rabbit sera. The statistically significant enhancement of anti-KLH IgG antibody appeared on the 14th day in the inbred strain of rabbits and increased through to the 35th day. An insignificant increase of total anti-KLH Ig was observed in the inbred rabbits compared to the outbred group during primary humoral response. The two groups of experimental animals were also different in their secondary immune response. The quantity of anti-KLH IgG antibody in the outbred stock was higher on the 7th day after the reimmunization than that at the peak of primary response. In contrast, in the group of inbred rabbits the quantity of anti-KLH IgG antibodies after second immunization reached the same level as in the primary immune response. The present results demonstrate that the first inbred generation can lead to differential adaptive humoral immune response to primary and secondary immunization with KLH.

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