Maria Helena Stangler Kraemer

Undifferentiated Spondyloarthropathies: A 2-Year Follow-up Study

Abstract: The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA). A prospective study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for seronegative spondyloarthropathies (SpA) and were aged between 18 and 50 years. Inclusion criteria included inflammatory low back pain (ILBP) (without radiographic sacroiliitis), asymmetric oligoarthritis (predominantly affecting large joints in the lower limbs) and heel enthesopathies (Achilles tendinitis and/or plantar fasciitis). Imaging methods included pelvic radiography (at study entry and after 2 years) and calcaneal radiography (at study entry). There was a predominance of male gender (78%), caucasoid race (72%) and positive HLA-B27 (54%), with a mean age of 31 years and mean disease duration of 5 years. The first disease manifestations were ILBP (49%), asymmetric oligoarthritis (35%) and heel enthesopathies (16%). A positive family history of a definite SpA was mentioned by 9% of the patients. Seventeen patients (25%) scored 5 points in the Amor set of SpA criteria; logistic regression analysis showed that HLA-B27, heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria ≥6, whereas ILBP was associated with Amor criteria <6. Male sex was associated with heel enthesopathies (p = 0.041) and ankle involvement (p = 0.015). Caucasoid race was associated with ILBP (p = 0.015) and buttock pain (p = 0.047). Positive HLA-B27 was associated with wrist involvement (p = 0.019) and Amor criteria ≥6 (p = 0.001). After a 2-year follow-up the following outcomes were observed: uSpA 75%; disease remission 13%; ankylosing spondylitis 10%; psoriatic arthritis 2%. Logistic regression analysis showed that buttock pain and positive HLA-B27 (trend) were statistically associated with progression to a definite SpA. In conclusion, uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease.

Model for human skin reconstructed in vitro composed of associated dermis and epidermis

CONTEXT AND OBJECTIVE The technique of obtaining human skin with dermis and epidermis reconstructed from cells isolated from patients can enable autologous skin grafting on patients with few donor sites. It also enables in vitro trials on chemicals and drugs. The objective of this work was to demonstrate a method for obtaining human skin composed of associated dermis and epidermis, reconstructed in vitro. DESIGN AND SETTING Experimental laboratory study, in the Skin Cell Culture Laboratory of Faculdade de Ciências Médicas, Universidade Estadual de Campinas. METHODS Cells from human fibroblast cultures are injected into bovine collagen type I matrix and kept immersed in specific culturing medium for fibroblasts. This enables human dermis reconstruction in vitro. On this, by culturing human keratinocytes and melanocytes, differentiated epidermis is formed, leading to the creation of human skin composed of associated dermis and epidermis, reconstructed in vitro. RESULTS We showed that human skin composed of associated dermis and epidermis can be successfully reconstructed in vitro. It is histologically formed in the same way as human skin in vivo. Collagen tissue can be identified in the dermis, with cells and extracellular matrix organized in parallel to multilayer epidermis. CONCLUSIONS It is possible to obtain completely differentiated human skin composed of associated dermis and epidermis, reconstructed in vitro, from injection of human fibroblasts into bovine collagen type I matrix and culturing of human keratinocytes and melanocytes on this matrix.

Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)‐alpha ‐238 and ‐308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long‐term follow‐up Brazilian study

Background  The strongest genetic marker for psoriasis is Cw*06. Polymorphisms in the tumor necrosis factor (TNF)‐alpha promoter region, especially replacement of guanine with adenine in positions ‐238 and ‐308 are related to higher TNF‐alpha production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We performed a case‐control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10‐years of follow‐up in mild or severe disease and determined HLA class I, II, and TNF single nucleotide polymorphisms (SNPs) ‐238 and ‐308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians.

Molecular identification of the HLA-DRB1-DQB1 for diagnosis and follow-up of acute leukemias.

We analyzed a group of 45 Brazilian individuals, 30 with acute myeloid leukemia (AML), 15 with acute lymphoid leukemia (ALL) and 100 healthy controls to assess genetic factor risk and HLA association contribution to the disease. Patient rates were compared with age and sex-matched control groups by directly typing the HLA-DRB1/3/4/5 and -DQB1 loci by PCR analysis. We observed significantly increased allelic distribution of HLA-DRB107 in AML patients and of HLA-DRB103 in ALL patients, which suggests that individuals in both groups are susceptible to the disease. We also found significantly decreased allelic distribution of HLA-DQB104 in AML patients and of HLA-DRB104 and -DQB103 in ALL patients, which suggests protection against the disease. We further found increased HLA-DRB107 and -DQB102 haplotypes in AML patients, which suggests susceptibility to the disease and decreased HLA-DRB104 and -DQB103 haplotypes in ALL patients, which also suggests protection against the disease. Future studies with larger and/or multicentric samples will be required for better comprehension of the HLA role in acute leukemia pathogenesis.

Long-standing idiopathic hypoparathyroidism masking coexistent chronic inflammatory demyelinating polyneuropathy.

Dear Editor, Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder directed against peripheral nerves, the precise pathogenesis of which is still unclear (Berger et al., 2003). Rarely, CIDP has been associated with neoplasia and immune-mediated conditions, although there are no previous reports about the association between isolated hypoparathyroidism and CIDP. We present a young patient with idiopathic hypoparathyroidism (IH) whose symptoms preceded and masked the manifestations of coexistent CIDP. An 18-year-old man came for evaluation because of generalized cramps and lower limb paresthesias in the last 6 years. The patient was 1.75 m tall and had a body mass index of 20 kg/m. A general clinical evaluation showed no abnormalities. He presented Chvostek and Trosseau’s signs but muscle tone and power were intact. Neurological examination revealed only mild vibration sense impairment below the ankles and hypoactive ankle reflexes. His medical history was unremarkable, and no familial case of neurological or endocrine disease was identified. Initial evaluation revealed undetectable parathyroid hormone levels with serum total and ionic calcium of 4.3 mg/dL (normal 8.6–10.0 mg/dL) and 0.65 mM (normal 1.11–1.32 mM), respectively. Inorganic phosphate was 8.3 mg/dL (normal 2.7–4.5 mg/dL) and 24 h urine calcium excretion was 94 mg (normal 100–300 mg). Serum protein electrophoresis, sodium, potassium, magnesium, albumin, creatine-kinase, lactate, serum folate, vitamin B12, and renal, hepatic, and thyroid function tests were within normal range. Cranial CT showed extensive basal ganglia calcification, and ophthalmologic evaluation disclosed bilateral cataracts. Calcium supplementation (4 g/day) and 1,25-(OH)2vitamin D3 (0.25 units three times daily) were started with prompt correction of calcium levels. For the next 8 months, there was marked clinical improvement with complete relief of symptoms. Only ankle reflexes remained hypoactive. In April 2003, he began to notice progressive difficulty in climbing stairs and return of numbness in feet. Over the following 8 weeks, numbness extended up to the knees and gait difficulties worsened. As calcium levels were normal, he was admitted for investigation. He presented moderate proximal and marked distal limb weakness with complete areflexia. There was distal loss of deep sensation in feet and gait ataxia with eyes closed. Electromyography (ENMG) demonstrated markedly slowed motor nerve conduction velocities and conduction blocks on multiple nerves. No sensory potential could be obtained and F-waves were absent. Needle electromyography showed scarce spontaneous activity and rare neurogenic motor unit action potentials but severely decreased recruitment. Cerebrospinal fluid (CSF) analysis showed increased protein (185 mg/dL) and immunoglobulin (Ig)G (29 mg/dL) levels without cells. A sural nerve biopsy revealed onion-bulb formations and ongoing demyelination, with scarce lymphocytic infiltrate. Prednisone was started (1 mg/kg/day), but after 6 weeks, deficits steadily worsened and the patient became wheelchair-bound. Intravenous Ig (IVIg), 0.4 g/kg/day for 5 days, was prescribed and clear improvement was soon noticed. He currently receives monthly IVIg infusions and maintenance doses of azathioprine (3 mg/kg/day), and there has been marked improvement in CSF analysis and nerve conduction studies. He now walks unassisted. Movement disorders, tetany, seizures, and dementia are particularly frequent in hypoparathyroidism. However, peripheral nervous system involvement is exceedingly rare. There are only four previous reports of hypoparathyroidism with neuropathy Address correspondence to: Marcondes C. França, Jr., Departamento de Neurologia, Faculdade de Ciências Médicas – UNICAMP, Cx. Postal 6111 CEP: 13083-970, Campinas, São Paulo, Brazil. Tel: þ55-19-3788-7507; Fax: þ55-19-3788-7483; E-mail: mcfjunior@ig.com.br Journal of the Peripheral Nervous System 9:196–197 (2004)