Disseminated crytococcosis with extensive cutaneous involvement in AIDS

Cutaneous infections is observed in 15% of patients with disseminated cryptococcosis with AIDS. We present here a case of a 34 years old female with AIDS. She presented with multiple skin coloured umbilicated over face, neck, trunk and limbs, which mimicked molluscum contagiosum and kaposi sarcoma. The tissue from cutaneous lesions was collected by excision biopsy and processed by standard mycological methods. Cryptococcus neoformans was isolated and identified. Cerebrospinal fluid (CSF) also yielded the growth of C. neoformans . Cryptococcal antigen was detected with a titre of 1024 by Latex agglutination, is serum and CSF. Her serum was reactive for HIVI and 2 antibodies. The CD4 lymphocytes count was 80/cmm. The HIV viral load was 2,48,084 copies/mL. She was treated with amphotericin B injectable and oral fluconazole. She responded well and lesions regressed.     

Two cases of mitochondrial myopathy with predominant respiratory dysfunction

Although it is well known that the respiratory failure is a major cause of death in most patients with chronic neuromuscular disease, predominant respiratory dysfunction without severe involvement of limb muscles is an unusual complication of mitochondrial myopathy in adult age. We experienced two cases of mitochondrial myopathy with severe involvement of respiratory function and only mild involvement of limb muscles. One is a 16 year old female and another is a 22 year old male. The diagnosis is based on morphologic characteristics of "ragged red fibers" under the light microscope and abnormal mitochondrias on the electron microscope in the muscle biopsy.     

Distal myopathy with rimmed vacuoles: impaired O-glycan formation in muscular glycoproteins

Distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with early adult onset, displays distal dominant muscular involvement and is characterized by the presence of numerous rimmed vacuoles in the affected muscle fibers. The pathophysiology of DMRV has not been clarified yet, although the responsible gene was identified as that encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase involved in the biosynthesis of sialic acids. To identify defective carbohydrate moieties of muscular glycoproteins from DMRV patients, frozen skeletal muscle sections from seven patients with DMRV, as well as normal and pathological controls, were treated with or without sialidase or N-glycosidase F followed by lectin staining and lectin blotting analysis. The sialic acid contents of the O-glycans in the skeletal muscle specimens from the DMRV patients were also measured. We found that Arachis hypogaea agglutinin (PNA) lectin reacted strongly with sarcolemmal glycoproteins in the DMRV patients but not with those in control subjects. alpha-Dystroglycan from the DMRV patients strongly associated with PNA lectin, although that from controls did not. The sialic acid level of the O-glycans in the DMRV muscular glycoproteins with molecular weights of 30 to 200 kd was reduced to 60 to 80% of the control level. The results show that impaired sialyl O-glycan formation in muscular glycoproteins, including alpha-dystroglycan, occurs in DMRV.     

Myeloma associated scleromyxedema with extensive involvement of small bowel.

The details of a patient with disseminated scleromyxedema related to multiple myeloma are presented. Investigation demonstrated extensive accumulation of mucopolysaccharides in the skin, bone marrow and the small bowel submucosa. The latter finding is a most unusual manifestation of scleromyxedema and appeared to correlate with the patient's symptoms on presentation.     

Motor unit changes in inflammatory myopathy and progressive muscular dystrophy

The aim of present study was to analyse the motor unit (MU) changes in progressive muscle dystrophy (PMD) and in inflammatory myopathy (IM) and to evaluate eventual neurogenic factors in MU reorganisation. The material consisted of 20 patients with (PMD), 20 patients with (IM) and 20 healthy age-matched volunteers. The shape of concentric needle motor unit potentials (cn MUPs), including their duration, amplitude, area, size index and number of phases, the interference pattern and the amplitude and area of macro MUPs were evaluated. The cn emg data satisfied the classical criteria for myopathy in all examined patients, at least in one of the tested muscles. A decreased amplitude and/or area of macro MUPs, compatible with myopathy, were observed in 32 of the 40 patients. In some cases of chronic IM and PDM the long duration polyphasic potentials were recorded. The size index (SI) value of long polyphasic MUPs was usually decreased or normal. This feature indicated that desynchronisation of "myopathic" MUPs results from a reduced number of muscle fibers and their degeneration and regeneration. The results indicated no difference in MU reorganization between PMD and IM and no evidence of neurogenic factors in MU changes.     

Cardiac involvement in Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy (EDMD) is a common form of muscular dystrophy frequently involving cardiac muscle, thus leading to dilated cardiomyopathy. Clinical outcome and prognosis is frequently determined by the involvement of the cardiac conduction system causing symptomatic bradyarrhythmias, as well as tachyarrhythmias and, if untreated, frequent sudden cardiac death. Typical features of the cardiac involvement of EDMD are presented, caused by a novel missense mutation in the splice receptor sequence of intron 6 of the LMNA gene on chromosome 1, encoding for the lamin A/C gene, consistent with the autosomal dominant form of EDMD.     

Altered expression of ARPP protein in skeletal muscles of patients with muscular dystrophy, congenital myopathy and spinal muscular atrophy.

OBJECTIVES: Ankyrin-repeated protein with PEST and a proline-rich region (ARPP) is a recently identified protein with 4 ankyrin-repeated motifs in its central portion. Type 1 myofibers of skeletal muscle express high levels of ARPP. Recently, we have found that ARPP expression was induced in mouse denervated skeletal muscle. This led us to hypothesize that ARPP expression might be induced in skeletal muscle under some pathological conditions. METHODS: In this study, we performed immunohistochemical analysis of ARPP expression in biopsy specimens of muscle tissue from 15 patients with muscular dystrophies (MDs), 13 with congenital myopathies and 11 with spinal muscular atrophies (SMAs). RESULTS: The ARPP expression levels of all the specimens from MD patients appeared to be lower than control muscle levels. In contrast, the specimens from the 13 patients with congenital myopathies were all ARPP positive. We also found increased numbers of ARPP-positive myofibers in patients with congenital myopathies, and these myofibers co-expressed the slow myosin heavy chain. Indeed, it has been reported that type 1 myofibers are predominant in patients with congenital myopathies, suggesting that increased numbers of ARPP-positive myofibers in such patients may be associated with increased numbers of type 1 fibers. In patients with SMAs, we found that ARPP-positive myofibers tended to be distributed in groups. As grouped myofibers have been reported to result from the process of denervation, innervation and subsequent denervation of re-innervated myofibers, the grouped ARPP-positive myofibers in SMA patients may result from denervation of the motor units. CONCLUSIONS: These findings suggest that evaluation of ARPP may be helpful for the histological diagnosis of muscle diseases.     

Early and extensive spinal white matter involvement in neuromyelitis optica

ObjectivesStudies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin‐4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO.MethodsWe analyzed 50 spinal cord lesions from eleven autopsied NMO/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3‐tesla MRI in 15 AQP4 antibody‐positive NMO/NMOSD patients and in 15 AQP4 antibody‐negative multiple sclerosis (MS) patients.ResultsPathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty‐four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, P ^corr = 0.020, and P ^corr = 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti‐AQP4 antibody‐seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, P ^corr = 0.005, and P ^corr = 0.043, respectively) and AQP4 antibody‐seronegative MS patients (86.7%, 73.3% and 33.3%, P ^corr = 0.063, and P ^corr = 0.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively.ConclusionsNMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions.     

Monocyte and macrophage Fc-receptor function in systemic vasculitis with renal involvement

The Fc-receptor function of macrophages and monocytes was studied in 10 healthy subjects and 10 patients (5 in phase of clinical activity) affected by systemic vasculitis with histological evidence of renal involvement. Macrophage function was detected by measuring the clearance in vivo of IgG-sensitized 51Cr-labelled autologous red blood cells (RBC). In vitro immune phagocytosis of monocytes was analysed as a kinetic phenomenon by incubating IgG-coated RBC with nearly pure suspensions of peripheral monocytes. All 5 patients studied in phase of clinical activity showed a defective Fc-receptor function in both the assays, as compared with normal subjects. Since a good correlation was found between the in vitro and the in vivo methods, the use of this non-invasive in vitro procedure is proposed as a substitute for the radioactive in vivo techniques in monitoring the course of the above disease.     

Skin involvement in cutaneous and systemic vasculitis

Cutaneous vasculitides are a heterogeneous group of inflammatory disorders affecting skin blood vessels. They may be triggered by several factors, such as infection or drug, or may be related to underlying disease, notably connective tissue or malignancies. However, vasculitis occurs without any demonstrable triggering agents in a relevant number of patients. On the other hand, vasculitic skin lesions may manifest as a component of vasculitis affecting also internal organs; in someone of these patients, skin involvement occurs initially as the sole sign of disease, leading to consider cutaneous vasculitis a diagnosis of exclusion. In this review, we have focused on the most common variants of cutaneous vasculitis, including cutaneous small vessel vasculitis and urticarial vasculitis as well as Henoch–Schönlein purpura, a systemic form in which however skin involvement often predominates. We have also argued on livedoid vasculopathy, a cutaneous entity which, although nonfrankly vasculitic in origin, is frequently associated with connective tissue disease. Finally, we have analyzed the variety of cutaneous manifestations that may develop during the course of the main systemic vasculitides, such as Wegener's granulomatosis, Churg–Strauss syndrome and polyarteritis nodosa.     

Toxic epidermal necrolysis with extensive mucosal erosions of the gastrointestinal and respiratory tracts

Toxic epidermal necrolysis with epidermal shedding over almost the entire body occurred in a patient with classical rheumatoid arthritis treated with sulindac, penicillamine and a combination analgesic containing paracetamol and chlormezanone. Erosions in the lower respiratory tract and the intestine contributed to a lethal outcome of the disease and showed a microscopical picture similar to that of the skin involved. The histopathological picture of these extracutaneous lesions have been only briefly reported previously.