Perivascular Mononuclear Infiltrates Research Articles

Dermatomyositis: A Rare Initial Presentation of Adenocarcinoma of the Prostate

There are only a few cases of dermatomyositis associated with urological malignancy reported in the literature. We report on a patient who presented with dermatomyositis as an early and sole manifestation of prostatic adenocarcinoma. To our knowledge this is the first such case reported in the literature. CASE REPORT A 63-year-old man presented with an erythematous rash on the scalp, neck, upper chest, back, extensor aspect of the elbow and gluteal region. The patient also had purple plaques over the back of his hand. A clinical diagnosis of dermatomyositis was made despite the absence of muscle weakness. Autoantibody screen and thyroid function tests were normal. Biopsy of skin from the back of the hand showed infiltration of the basal layer of epidermis with lymphocytes, with upper dermal and perivascular mononuclear infiltrate. Mucin stains demonstrated an increased amount of acid mucin in the papillary and upper reticular dermis, confirming the diagnosis of dermatomyositis. The patient had no other symptoms, and screening for internal malignancy did not reveal any primary tumor. He was started on oral steroids, which resulted in marked improvement of the skin lesions. The patient was followed regularly, and 14 months after initial presentation he complained of urinary frequency, nocturia and poor flow. Digital rectal examination showed a moderately enlarged firm prostate with no nodules. Prostate specific antigen (PSA) was 100 g./l. Acute urinary retention subsequently developed, and transurethral prostatectomy was performed. Histological examination demonstrated prostatic adenocarcinoma (Gleason score 9). Hormonal ablative therapy with cyproterone acetate and goserelin was commenced. Staging computerized tomography revealed a 5 5 5 cm. prostate infiltrating the floor of the bladder, pelvic side wall and left side of the rectum. The seminal vesicles were involved with multiple enlarged lymph nodes measuring up to 2 cm. Bone scan showed metastases to the pelvis, spine and ribs. With hormonal ablative therapy PSA dropped to 4.3 g./l. and oral steroids were discontinued. Within a few months of starting treatment the skin lesions disappeared, with the exception of the plaques on the back of the hand. DISCUSSION

Sensory-predominant, painful, idiopathic neuropathy: inflammatory changes in sural nerves.

Sensory-predominant, painful, idiopathic neuropathies are a common clinical problem. In this retrospective study of 11 patients with such a neuropathy, we found axonal loss in 9, with multifocal axonal loss in 4 patients; there were large perivascular mononuclear inflammatory infiltrates (>50 cells) in 4 and smaller infiltrates (10-20 cells) in 4. These findings suggest that some cases of this neuropathy may be due to autoimmune vasculopathy and therefore may respond to immunotherapy.

Peripheral Nervous System Manifestations of Lyme Borreliosis

Lyme disease is a tick-borne illness that has protean neurologic manifestations involving both the central and peripheral nervous system. The peripheral nervous system manifestations of Lyme borreliosis can be divided chronologically into acute and chronic forms. Within weeks after disease onset, approximately 15% of untreated patients develop an acute Lyme meningoradiculoneuritis with headache, fever, radicular pain, weakness, and sensory loss, often associated with cranial neuropathy, usually facial palsy. Cerebrospinal fluid typically shows lymphocytic pleocytosis, high protein, and normal glucose. Diagnosis is made by recognition of characteristic clinical features with a history of preceding exposure and confirmed by serologic evidence of exposure to B. burgdorferi or by antibody or PCR evidence of cerebrospinal fluid infection. Months to years after onset, rare patients may develop chronic polyradiculoneuropathy presenting with sensory symptoms or radicular pain. Diagnosis is confirmed by a history of exposure, previous systemic or acute neurologic manifestations of Lyme borreliosis, and serologic evidence of infection. Pathology of acute or chronic Lyme radiculoneuropathy reveals axonal degeneration with perivascular mononuclear infiltration. Eradication of the organism can be achieved with 2 to 4 weeks of ceftriaxone for both acute and chronic Lyme neuroborreliosis. Isolated facial palsy without evidence of cerebrospinal fluid infection can be treated with oral antibiotics such as doxycycline. Prognosis after therapy is good, but neurologic recovery is slower for chronic than acute Lyme radiculoneuropathy.

Mycoplasma pneumoniae induces chronic respiratory infection, airway hyperreactivity, and pulmonary inflammation: a murine model of infection-associated chronic reactive airway disease.

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r = -0.95, P = 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P = 0.03) and increased airway obstruction at 530 days (P = 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.

Scleroderma fibroblasts promote migration of mononuclear leucocytes across endothelial cell monolayers.

Perivascular infiltrates of inflammatory cells are a hallmark of lesional skin in scleroderma. We have explored the potential for scleroderma fibroblasts to modulate mononuclear leucocyte migration across endothelial cell monolayers in tissue culture, and to regulate expression of endothelial cell adhesion molecules. Fibroblasts were grown from skin biopsies of eight patients with active diffuse cutaneous scleroderma and from four healthy controls. Co-culture and conditioned medium transfer experiments examined the effect of soluble fibroblast products on mononuclear leucocyte (U937) cell migration across endothelial cell (1E-7) monolayers grown on tissue culture inserts. Co-culture of scleroderma, but not control fibroblasts, promoted transendothelial migration of U937 cells. Scleroderma fibroblast-conditioned medium had qualitatively similar effects and equivalent results were obtained using Jurkat-6 (T lymphocyte) cells, and with peripheral blood mononuclear cells from a patient with diffuse cutaneous scleroderma. Promotion of leucocyte migration does not appear to result from increased endothelial adhesion molecule expression, since fibroblast-conditioned medium did not up-regulate endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. Moreover, leucocyte migration across cytokine-activated endothelial cell layers in co-culture with fibroblasts was less than across resting cells, although the selective effect of scleroderma fibroblast co-culture persisted. Recombinant monocyte chemoattractant protein-1 (MCP-1) or IL-8 increased passage of mononuclear leucocytes across endothelial cell monolayers, whilst anti-MCP-1, but not anti-IL-8 antibodies, significantly reduced the effect of fibroblast conditioned medium. These data suggest that systemic sclerosis (SSc) fibroblasts promote leucocyte migration across endothelial cell monolayers in tissue culture via an MCP-1-dependent mechanism. These findings may be relevant to the perivascular mononuclear leucocyte infiltrates characteristic of early SSc lesions.

Antiphospholipid syndrome: ultrastructure of microvascular endotheliocytes in musculocutaneous bioptates during systemic lupus erythematosus.

Degeneration and atrophy of the epidermis, disorganization of the connective tissue, focal atrophy of skeletal myocytes, and diffuse vasculopathy are the main pathomorphological signs found in musculocutaneous bioptates during the antiphospholipid syndrome associated with systemic lupus erythematosus. The major morphogenetic disorder is alteration of microvascular endotheliocytes accompanied by the formation of concentric perivascular mononuclear infiltrates.

Captopril and platelet-activating factor (PAF) antagonist prevent cardiac allograft vasculopathy in rats: role of endogenous PAF and PAF-like compounds

Accelerated coronary artery disease (CAD) is the leading cause of late mortality following cardiac transplantation. The vascular lesions are characterized by myointimal proliferation and perivascular mononuclear inflammatory infiltrates. Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator produced by inflammatory cells and activated endothelial cells. Angiotensin II is known to activate phospholipase A 2, a critical enzyme in PAF synthesis. Using a rat heterotopic cardiac transplant model known to induce graft CAD, we previously reported that chronic administration of captopril, an angiotensin converting enzyme inhibitor, reduces intimal proliferation and maintains luminal patency. The purpose of the current study was to determine if captopril regulates vascular remodeling by suppressing PAF synthesis and whether administration of a PAF antagonist ameliorates graft CAD. Captopril was found to decrease levels of PAF and PAF-like compounds as well as reduce intimal lesions, decrease cellular rejection grade, and diminish allograft heart weights. Treatment with a PAF antagonist significantly decreased proliferation of the intimal component of the vasculopathy and caused regression of the cardiac hypertrophy, but had no significant effect on cellular rejection. In contrast, untreated animals had elevated plasma PAF levels, elevated heart weights, and severe myointimal proliferation with luminal stenosis 21 days post-transplantation. These observations suggest that graft CAD is mediated, in part, by PAF and PAF-like compounds, and suppression of endogenous PAF may prevent cardiac allograft vasculopathy.

A 6-year-old child with vacant episodes and unilateral convulsions

A previously well 6-year-old girl was admitted to hospital in May, 1998, after having a vacant episode followed by right-sided upper and lower limb clonic movements lasting 30 s. She was feverish (38·6°C), neurological examination was normal, and she had no meningism. There was a leucocytosis (22·7 × 109/L, 70% neutrophils) and she had an Escherchia coli urinary-tract infection. She was given trimethoprim and discharged home the next day, to be readmitted 12 h later with further fits. She had no fever and physical examination and white-cell count were normal. She had several complex partial seizures. An electroencephalogram showed left frontotemporal sharp waves. Carbamazepine stopped her fits. 10 days after she became ill, a magnetic resonance imaging (MRI) scan showed a left frontal-lobe lesion of uncertain aetiology (figure A). She remained afebrile, well, and lively. Her white-cell count was 12·109L, ESR 30 mm/h, and C-reactive protein 20 mg/mL. Cerebrospinal fluid (CSF) showed no cells, and normal protein (0·08 g/L) and glucose (3·4 mmol/L; serum glucose 5·0 mmol/L). Intravenous acyclovir and ceftriaxone were started. There was no known contact with tuberculosis and no immunodeficiency. 48 h after starting acyclovir and ceftriaxone she deteriorated, with vomiting and drowsiness. A repeat MRI scan showed extension of the lesion with oedema and midline shift (figure B). CSF was sterile and PCR for herpes simplex virus (HSV), varicella zoster virus, and enterovirus were negative. Metronidazole was added. A brain biopsy showed a diffuse mononuclear leptomeningeal and perivascular infiltrate and was bacteriologically sterile.

Sequential expression of transforming growth factor-beta1 by T-cells, macrophages, and microglia in rat spinal cord during autoimmune inflammation.

Transforming growth factor-beta1 (TGF-beta1) is crucially involved in regulating inflammatory events during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Despite accumulating evidence for local expression of TGF-beta1 in the inflamed nervous system, uncertainty remains regarding its cellular source. We have investigated the temporospatial distribution of TGF-beta1 gene expression in rat spinal cord during EAE. In actively induced EAE, in situ hybridization revealed strong expression of TGF-beta1 in meningeal and perivascular mononuclear infiltrates at onset of the disease, continued expression in perivascular infiltrates and scattered mononuclear cells at maximal disease severity, and expression in scattered parenchymal cells during recovery. Double labeling studies revealed subpopulations of infiltrating T-cells to be the major source of TGF-beta1 early in the disease, followed by macrophages at peak severity and microglial cells during the recovery phase of EAE. Astrocytes and neurons did not express TGF-beta1. Quantification of mRNA by Northern blot analysis revealed that cellular expression of TGF-beta1 by T-cells, macrophages, and microglia sums up to a long-lasting elevation of TGF-beta1 mRNA extending well into the recovery phase. Our data indicate cellular diversity and suggest functional diversity of TGF-beta1 gene expression during EAE. While TGF-beta1 expressed early in the disease by T-cells may contribute to inflammatory lesion development, microglial cells may potentially contribute to recovery by expressing immunosuppressive TGF-beta1 during remission.

Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin

In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from systemic sclerosis patients compared with healthy volunteers. ICAM-1 was localized to vessels and perivascular mononuclear infiltrates by immunohistochemical methods. IL-2R was expressed by CD3-positive cells. The elevated levels of sICAM-1 and sIL-2R in suction blister fluid point towards activation of endothelial cells and T cells in both the transition zone and uninvolved skin of systemic sclerosis patients.

A histological and immunohistochemical study on chronic irritant contact dermatitis

Background: Chronic irritant contact dermatitis (CICD) is characterized by erythema, scaling, hyperkeratosis, chapping and fissures. It may be the result of skin damage evoked by the cumulative effect of a variety of irritant stimuli. The diagnosis of CICD is made on basis of the patient's history and clinical features. No specific diagnostic tests are available. Objective: The histopathologic and cell biological features of CICD have not been extensively studied. Here, we describe the histological and immunohistological changes in CICD. Methods: Punch biopsies were taken from 11 patients with CICD for hematoxylin eosin and immunohistochemical stainings. Four skin biopsies of the palms of the hands of healthy volunteers served as controls. Results: The histopathologic pattern was characterized by different grades of hyperkeratosis, parakeratosis, spongiosis, exocytosis, acanthosis, and mononuclear perivascular infiltrates. Mitotic activity, as measured by Ki-67-staining in the epidermis, was increased fourfold in involved skin as compared with normal skin. Involucrin, a structural protein of the cornified envelope, was expressed from the stratum granulosum throughout the stratum spinosum in all patients with CICD and was upregulated in comparison with normal skin. Epidermal fatty-acid binding protein (E-FABP), a terminal differentiation marker, was proportionally unaltered in the CICD as compared with the normal skin and was localized from the stratum granulosum to the upper layers of the stratum spinosum. Cytokeratin 16, a differentiation marker expressed in hyperproliferative epidermis, was markedly increased from the stratum granulosum throughout the stratum spinosum in 5 out of 11 patients with CICD. Skin-derived antiproteinase (SKALP)/elafin, a proteinase inhibitor expressed in inflamed epidermis, was only detected within the stratum granulosum in 3 out of 11 patients. Conclusion: We conclude that CICD is clinically characterized by features of a chronic dermatitis and, at the histological level, by inflammatory changes, epidermal hyperproliferation and altered differentiation.

A Histological and Immunohistochemical Study on Chronic Irritant Contact Dermatitis

Background: Chronic irritant contact dermatitis (CICD) is characterized by erythema, scaling, hyperkeratosis, chapping and fissures. It may be the result of skin damage evoked by the cumulative effect of a variety of irritant stimuli. The diagnosis of CICD is made on basis of the patient's history and clinical features. No specific diagnostic tests are available. Objective: The histopathologic and cell biological features of CICD have not been extensively studied. Here, we describe the histological and immunohistological changes in CICD. Methods: Punch biopsies were taken from 11 patients with CICD for hematoxylin eosin and immunohistochemical stainings. Four skin biopsies of the palms of the hands of healthy volunteers served as controls. Results: The histopathologic pattern was characterized by different grades of hyperkeratosis, parakeratosis, spongiosis, exocytosis, acanthosis, and mononuclear perivascular infiltrates. Mitotic activity, as measured by Ki-67-staining in the epidermis, was increased fourfold in involved skin as compared with normal skin. Involucrin, a structural protein of the cornified envelope, was expressed from the stratum granulosum throughout the stratum spinosum in all patients with CICD and was upregulated in comparison with normal skin. Epidermal fatty-acid binding protein (E-FABP), a terminal differentiation marker, was proportionally unaltered in the CICD as compared with the normal skin and was localized from the stratum granulosum to the upper layers of the stratum spinosum. Cytokeratin 16, a differentiation marker expressed in hyperproliferative epidermis, was markedly increased from the stratum granulosum throughout the stratum spinosum in 5 out of 11 patients with CICD. Skin-derived antiproteinase (SKALP)/elafin, a proteinase inhibitor expressed in inflamed epidermis, was only detected within the stratum granulosum in 3 out of 11 patients. Conclusion: We conclude that CICD is clinically characterized by features of a chronic dermatitis and, at the histological level, by inflammatory changes, epidermal hyperproliferation and altered differentiation.

Treatment of Autoimmune Disease by Oral Tolerance to Autoantigens

Multiple sclerosis (MS) is a chronic demyelinating disease of the human central nervous system (CNS) which can be characterized clinically by a remitting–relapsing or a chronic progressive course. There is a striking similarity between the clinical and histopathological features of MS and the experimentally induced disease, experimental autoimmune encephalomyelitis (EAE). Induced by the injection of myelin basic protein (MBP) and adjuvants, EAE is characterized by clinical neurologic signs of paralysis and histopathologic changes consisting of perivascular mononuclear infiltration and demyelination. We have reported that the oral administration of MBP exerts a profoundly suppressive effect on EAE induced in the Lewis rat. This MBP-induced oral tolerance is characterized by an inhibition of EAE clinical neurologic signs, reduced CNS histopathologic changes, a profound decrease in the T-lymphocyte proliferative response specific for the fed antigen, and a decrease in serum antibody specific for MBP. In a chronic relapsing model of EAE in the B10.PL mouse, we have shown that the oral administration of MBP either prior to MBP challenge or on the first day of clinical signs results in a decreased number and severity of EAE relapses. The oral tolerance approach has also proven effective in the suppression of other organ-specific autoimmune diseases including collagen-induced arthritis, adjuvant arthritis, uveoretinitis, experimental myasthenia gravis, diabetes, and thyroiditis as well as graft rejection. Two primary mechanisms have been proposed to explain oral tolerance in EAE-active suppression following feeding of lower doses of antigen and clonal anergy or deletion following administration of higher doses.In vivoapproaches in rats and transgenic mice have been used to further explore the mechanisms underlying oral tolerance. Administration of recombinant interleukin (IL)-2 was shown to reverse the tolerance induced by feeding low doses of MBP, but not the tolerance induced by feeding high doses of MBP, indicating that deletion had occurred in the high-dose group. Moreover, the oral administration of MBP to MBP-specific T-cell receptor (TCR) transgenic mice resulted in a profound decrease of the transgenic T cells in the blood, lymph node cells (LNC), mesenteric LNC, and spleen compartments. The proliferative response to MBP was also profoundly reduced in these organs, indicating that the cells had been deleted from these sites. The results achieved in animal models have led to clinical trials of oral tolerization in three human autoimmune diseases—MS, uveoretinitis, and rheumatoid arthritis—with promising results.

Cytokines and systemic sclerosis

T he defining pathologic features of systemic sclerosis (SSc) include excessive extracellular matrix deposition and a mononuclear perivascular infiltrate, usually involving both the skin and internal organs and capable of microvascular obliteration. Studies of the pathogenesis of SSc have implicated a role for monocytes, macrophages, T-lymphocytes, the endothelium, and fibroblasts communicating via a complex autocrine and paracrine network of cytokines. The etiology of SSc is unknown. Most hypotheses for SSc have included (1) activation of the immune system leading to fewer CD8 cytolytic and more helper-inducer CD4 T-lymphocytes; (2) endothelial injury/activation leading to edema, vasomotor instability, increased permeability, and distinctive microvascular lesions; and (3) vascular intimal and parenchymal interstitial fibrosis. There is peril in attempting to focus the panoply of information regarding cytokines meaningfully in the direction of any one of the rheumatic or diffuse connective tissue diseases. There are many cytokines, each is expressed in precurser form requiring activation, cytokinebinding proteins are being defined in profusion with ever-increasing impact on the presumed biological role of the cytokine under discussion, and, perhaps most important, cells respond differently to cytokine A when they have previously been exposed to cytokine B. This imprinting of prior cytokine effects can persist for days and through several population doublings, at least in vitro. These are but a few of the pitfalls that threaten any attempt to draw meaningful conclusions from the cytokine cascade in 1994. To make this task more manageable, the

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model of multiple sclerosis. Demyelination is linked to persistent TMEV infection of the central nervous system and characterized by perivascular inflammatory mononuclear infiltrates and primary demyelination. Our previous results have shown that susceptibility correlates with the temporal development of chronic virus-specific delayed-type hypersensitivity (DTH) responses and suggest that inflammatory processes mediated by T cells specific for an immunodominant determinant on virus capsid protein 2 (VP2(74-86)) play a major immunopathologic role in SJL/J mice. In this study we have further defined the T cell-dependent nature and specificity of the demyelinating process in susceptible SJL/J mice by showing that thymectomized irradiated bone marrow-restored mice fail to develop chronic demyelination and that i.v. adoptive transfer of polyclonal TMEV-specific T cells before intracerebral infection with a suboptimal dose of the BeAn strain of TMEV led to increased incidence and accelerated onset of clinical disease. The data also show that demyelination is dependent on the activity of virus-specific CD4+ T cells because in vivo depletion with anti-CD4, but not anti-CD8, mAb led to significantly diminished incidence and severity of demyelination concomitant with a decrease in TMEV-specific DTH reactivity. In addition, the adoptive transfer of a TMEV-specific, DTH-mediating CD4+ I-A(s)-restricted Th1 line (sTV1) specific for the immunodominant VP2(74-86) epitope also led to increased incidence and accelerated onset of clinical disease only in TMEV-infected recipients. Collectively, the results of this and the companion paper demonstrate the highly significant immunopathologic contribution of CD4+ T cell responses specific for an immunodominant viral epitope to the chronic central nervous system demyelination observed in TMEV-infected SJL/J mice.

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. V. Mapping of a dominant immunopathologic VP2 T cell epitope in susceptible SJL/J mice.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model of multiple sclerosis. Demyelination is linked to persistent TMEV infection of the central nervous system and characterized by perivascular inflammatory mononuclear infiltrates and primary demyelination. Myelin damage is a T cell-dependent process and susceptibility correlates with the temporal development of chronic virus-specific delayed-type hypersensitivity (DTH) responses. Our previous results have shown that inflammatory processes mediated by Th1 cells specific for a determinant(s) on virus capsid protein 2 (VP2) play a major immunopathologic role in SJL/J mice. This study identifies a 13 amino acid peptide on VP2 (VP2(74-86)) as the immunodominant T cell epitope in TMEV-infected and -immunized SJL/J mice, and demonstrates the ability of that sequence to prime for the majority of the SJL/J DTH T cell response to intact TMEV. The importance of T cell responses to this epitope in the demyelinating process was illustrated by experiments in which SJL/J mice displayed an increased incidence and accelerated onset of clinical disease after peripheral immunization with a fusion protein containing VP2(74-84) before intracerebral infection with a suboptimal dose of the BeAn strain of TMEV. Identification of this immunopathologic TMEV T cell epitope will be critically important for delineation of the mechanisms of T cell-mediated myelin damage and for potential use to prevent and/or treat TMEV-induced demyelinating disease via the induction of epitope-specific tolerance.

Febrile Ulceronecrotic Mucha‐Habermann's Disease

Febrile ulceronecrotic Mucha-Habermann's disease (FUMH) was first described by Degos in 1966. In the literature, nine cases of FUMH have been reported in both children and adults. We report a 16-year-old boy with the febrile ulceronecrotic type. A review of the nine cases in the literature showed acute necrotic lesions, as well as rare complications such as fever, superinfected lesions and viral infection which are not as common in pityriasis lichenoides et varioliformis acuta. There is no definitive treatment, but systemic corticosteroid, methotrexate, antibiotics (tetracycline, erythromycin), aciclovir, and 4,4-diaminodiphenyl sulfone (DDS) have been frequently used. The most common histologic feature is mononuclear perivascular infiltrates consisting of T lymphocytes. The etiology is not known, but a hypersensitivity reaction, possibly to an infectious agent, is suggested.

Biocompatibility of Polyethylene and Host Response to Loosening of Cementless Total Hip Replacement

A human lymphocyte culture protocol was used to identify the biocompatibility pattern of fine particulate ultra-high molecular weight polyethylene. Polyethylene did not cause an increase in lymphocyte DNA synthesis as assessed by the 3H-thymidine incorporation method on culture Days 1, 3, nor 5. As analyzed with monoclonal activation markers, the polyethylene dependent expression of major histocompatibility complex (MHC) class II antigen as well as interleukin-2 receptor (CD25) was virtually nonexistent. An apparent increase in the amount of CD11b positive monocytes/macrophages from 7% +/- 2% to 22% +/- 6% was recorded. Samples of pseudocapsules of the totally replaced hips (THR) obtained at revision operations for aseptic loosening of cementless prostheses with polyethylene lining of the acetabular component, were obtained from ten patients for immunopathologic studies. In seven cases the prostheses consisted of chromium-cobalt-molybdenum steel alloy and in three cases of titanium. Revisions were performed on average 4.6 years (range, 2.5-7) after insertion of the prostheses. The predominant cell in the lining cell layer of the periprosthetic cavity was in each case the CD11b, CD68, and nonspecific esterase positive but endogenous peroxidase-negative macrophage. Proline 4-hydroxylase positive fibroblasts dominated the stroma that was also inhabited by usually perivascular mononuclear cell infiltrations of mainly CD11b/CD68 phenotype with occasional CD4-positive cells. Only few mononuclear cells were activated CD25 positive T cells or CD19-positive B-lymphocytes. In titanium-based THRs, the cytoplasm of the macrophages contained a large number of small metallic particles, although this phenomenon was not seen in chromium-cobalt-molybdenum steel-based THRs. Fine particulate ultra-high molecular weight polyethylene is immunologically relatively insert. Nevertheless, it causes a clear foreign body type of phenomenon in vitro. The loosening of cementless acetabular components was associated with CD11b- and CD68-positive macrophage reaction in the pseudocapsular tissue. In any case, there is no clinical or experimental evidence to suggest that the use of cementless THR prostheses with polyethylene sockets would prevent an adverse biologic host response.

Dengue. Muscle biopsy findings in 15 patients.

Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the brazilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.

Progressive Multifocal Leukoencephalopathy (PML) in the Acquired Immunodeficiency Syndrome (AIDS): A Neuropathological Autopsy Study of 21 Cases

In a neuropathological autopsy study of 21 cases of AIDS-associated PML no fundamental morphological differences to non-AIDS PML were found. PML in AIDS often showed very large foci as well as necrotizing lesions. Partial involvement of cerebral cortex and deep gray matter were common findings; infratentorial lesions could be observed in more than three quarters of cases. Perivascular mononuclear infiltrates within PML foci were frequent and obviously not associated with a more benign clinical course. Possible reasons for these peculiarities of PML in AIDS are discussed. In 7 cases evidence of concomitant HIV encephalopathy was found; this may be one relevant factor contributing to severity of PML in AIDS. PML has to be regarded as a common complication of HIV infection, which may show atypical morphological and neuroradiological features.