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Suspected necrolytic migratory erythema associated with chronic hepatopathy in a cat.

A cat presenting with generalised hypotrichosis and crusts on the feet and tail was found to have an unusual chronic hepatopathy. There was also evidence of a chronic small intestinal disease which went undiagnosed. Necrolytic migratory erythema was suspected based on clinical findings and dermatohistopathology, and an association with the chronic hepatopathy was suggested. This is the first report of such an association in a cat. Serum zinc, amino acids and essential fatty acids were analysed, and medical treatment was given with equivocal efficacy.

Amino Acids↗

Evidence for circulating immune complexes in erythema nodosum and early sarcoidosis.

Twenty-two patients were investigated during acute attacks of erythema nodosum with a series of tests for circulating immune complexes. Nineteen had bilateral hilar lymphadenopathy and were considered to have sarcoidosis. Evidence of circulating immune complexes was found in 18, out of 22 patients (including 15 out of the 19 cases of sarcoidosis). The most frequent abnormality was the detection of elevated levels of C3 breakdown products (C3i), which were found in 14 out of 18 tests. The test results returned gradually to normal as symptoms subsided in 20-40 days, but 2 patients still showed abnormalities at 40 days despite the disappearance of symptoms. It is concluded that free immune complexes appear in the circulation during the early stages of acute sarcoidosis and gradually disappear as symptoms subside.

Antigen-Antibody Complex↗

Treatment of erythema chronicum migrans of Lyme disease.

Between June 1981 and July 1987 the efficacy of antibiotic treatment of 215 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. The principal antibiotics utilized to treat 161 patients through 1986 were varying doses of tetracycline, or penicillin alone or in combination with probenecid. Two of 80 patients with a minor form of the illness and 17 of 81 patients with a major form of the illness required retreatment. There were four patients who did not respond to retreatment with their original medication. A 15- to 30-day course of amoxicillin (500 mg q.i.d.) and probenecid (500 mg q.i.d.) or doxycycline (100 mg t.i.d.), and on three occasions ceftriaxone (2-4 g/day i.v.), were used to treat 54 patients in 1987. Although it is too early to judge the efficacy of treatment in these patients, increases in the incidence of Herxheimer reactions and drug eruptions were observed. Strict compliance with treatment protocols and the possibility of reactions to medications should be thoroughly discussed with patients.

Adult↗

Ultraviolet erythema sensitivity in anamnestic (I-IV) and phototested (1-4) Caucasian skin phototypes: the need for a new classification system.

The anamnestic skin phototypes (ASP) I-IV of 22 Caucasian volunteers wee compared with their phototested skin phototypes (PSP) using solar simulating, broadband UV radiation. The Commission Internationale de l'Eclairage (CIE)-weighted (i.e. erythemally effective) minimal erythema doses (MED) for solar simulating radiation varied from 20 mJ/cm2 (PSP type 1) to 57 mJ/cm2 (PSP type 4). In only 11 of 21 volunteers did the ASP (I-IV) and PSP (1-4) classifications coincide, and the MED values of the volunteers within the different ASP groups (I-IV) overlapped considerably. To compare the reactivity to erythematogenic radiation of different wavelengths, narrowband monochromator irradiations were performed at 298 nm, 310 nm and 330 nm. The CIE-weighted MED values at these wavelengths (20-80 mJ/cm2) corresponded well with those obtained in the broadband testing. Our results indicate that, with classification by interrogation, Caucasian skin can reliably be classified into only two subtypes, corresponding to Fitzpatrick phototypes I-III and phototype IV, respectively. A classification into four sensitivity types can be achieved by phototesting, only. We propose that the concept of ASP should be used with caution. The concept of PSP 1-4 should be favored.

Classification↗

Erythema multiforme: a literature review and case report.

Erythema multiforme is a florid mucocutaneous disease characterized by oral, cutaneous, and ocular manifestations. The cutaneous lesions are pathognomonic because of their unique "target-like" appearance. A severe form of EM has been termed "Stevens-Johnson Syndrome". Although the etiology of EM is unknown, much of the research suggests an immunological association with HSV. The diagnosis of EM is based on signs and symptoms, and a differential diagnosis should include other ulcerative, mucocutaneous diseases, such as erosive lichen planus, pemphigus, varicella zoster, ANUG, TEN, aphthous stomatitis, and primary HSV. Therapeutic measures are palliative, including a soft bland diet, topical anesthetics, and corticosteroids. A case of EM is described which underscores the appearance of the disease and its clinical course.

Adult↗

[Sero-diagnosis for human parvovirus B19 infection by IgM and IgG antibody capture method of enzyme-linked immunosorbent assay--study on an epidemic case of erythema infectiosum].

The IgM and IgG antibody capture methods of the enzyme-linked immunosorbent assay (ELISA) for human parvovirus B19 were performed using Horseradish peroxidase (HRPO)-labeled anti B19 monoclonal antibody. Serially obtained serum samples from one erythema infectiosum (E.I.) patient were examined at once by this methods. The dOD values of the IgM and IgG antibodies decreased on the typical curves according to the course of recovery. In the epidemic case of E.I. among students of one nurse school, 1) The first patients was estimated by comparing the change of dOD values of sera obtained at end of the epidemic and 1.5 months later. 2) In the pre-existing antibody positive persons, the dOD values of IgG antibody did not changed during the epidemic. 3) After the E.I. epidemic, and approximately 30% of the students were remained uninfected.

Antibodies, Viral↗

[Five family members infection likely due to human parvovirus B19 (erythema infectiosum)].

We encountered five members of the same family infected with parvovirus B19. The latency period in these patients was 17 to 20 days, which matched that observed by Anderson et al. after inoculating humans with the virus. The latency period in 24 cases of familial infection observed in 17 families at the same time showed peaks at both 10 days and 20 days. Thus, it is still necessary to determine the actual latent period of erythema infectiosum infection.

Adult↗

[Human parvovirus B19 infection which first presented with petechial hemorrhage, followed by papular-purpuric gloves and socks syndrome and erythema infectiosum].

A case of human parvovirus B19 (B19) infection is reported. A 6-year-old previously healthy girl was admitted to our hospital complaining of slight fever and petechial hemorrhage on her neck, trunk and the proximal parts of extremities. On admission, the platelet count was within normal range (180 x 10(3)/microliter) but white blood cells and reticulocytes were moderately suppressed (2.4 x 10(3)/microliter and 1@1000, respectively). The purpura disappeared in a week and the blood cell counts fully recovered without any specific treatment. Detection of B19 DNA and anti-B19 IgM antibody in the serum on admission led to the final diagnosis. Since the cellular receptor for B19, the blood group P antigen, is expressed on vascular endothelial cells as well as erythroid progenitor cells, the purpura was considered to be the result of direct vascular injury. She was very unique as she subsequently exhibited papular-purpuric gloves and socks syndrome and erythema infectiosum during follow-up. This case may provide a new insight into the pathogenesis of cutaneous manifestations of B19 infection.

Child↗

Erythema chronicum migrans and Lyme arthritis: cryoimmunoglobulins and clinical activity of skin and joints.

We report the presence of serum cryoimmunoglobulins in patients with attacks of a newly described epidemic arthritis--Lyme arthritis--and in some patients with a characteristic skin lesion--erythema chronicum migrans--that sometimes precedes the onset of the arthritis. Seven patients who had cryoimmunoglobulins at the time of the skin lesion have developed arthritis; four patients without them have not. The cryoglobulins in patients with the skin lesion consisted primarily of immunoglobulin M (IgM); those in patients with arthritis often included both IgM and IgG. These findings support the hypothesis that a common origin exists for the skin and joint lesions and suggest that circulating immune complexes may have a pathogenetic role in Lyme arthritis.

Adult↗

In vitro susceptibility testing of Borrelia burgdorferi sensu lato isolates cultured from patients with erythema migrans before and after antimicrobial chemotherapy.

Clinical treatment failures have been reported to occur in early Lyme borreliosis (LB) for many suitable antimicrobial agents. Investigations of possible resistance mechanisms of the Borrelia burgdorferi complex must analyze clinical isolates obtained from LB patients, despite their receiving antibiotic treatment. Here, borrelial isolates obtained from five patients with erythema migrans (EM) before the start of antibiotic therapy and again after the conclusion of treatment were investigated. The 10 isolates were characterized by restriction fragment length polymorphism analysis and plasmid profile analysis and subjected to susceptibility testing against a variety of antimicrobial agents including those used for initial chemotherapy. Four out of five patients were infected by the same genospecies (Borrelia afzelii, n = 3; Borrelia garinii, n = 1) at the site of the EM lesion before and after antimicrobial therapy. In one patient the genospecies of the initial isolate (B. afzelii) differed from that of the follow-up isolate (B. garinii). No significant changes in the in vitro susceptibilities became obvious for corresponding clinical isolates before the start and after the conclusion of antimicrobial therapy. This holds true for the antimicrobial agents used for specific chemotherapy of the patients, as well as for any of the additional agents tested in vitro. Our study substantiates borrelial persistence in some EM patients at the site of the infectious lesion despite antibiotic treatment over a reasonable time period. Borrelial persistence, however, was not caused by increasing MICs or minimal borreliacidal concentrations in these isolates. Therefore, resistance mechanisms other than acquired resistance to antimicrobial agents should be considered in patients with LB resistant to treatment.

Adult↗

Serologic evaluation of patients from Missouri with erythema migrans-like skin lesions with the C6 Lyme test.

Southern tick-associated rash illness (STARI), also known as Masters disease, affects people predominantly in the Southeast and South Central United States. These patients exhibit skin lesions that resemble erythema migrans (EM), the characteristic skin lesion in early Lyme disease. The etiology of STARI remains unknown, and no serologic test is available to aid in its diagnosis. The C6 Lyme enzyme-linked immunosorbent assay was used to evaluate coded serum specimens from patients with STARI at two laboratory sites. The specimens tested at one site consisted of acute- and convalescent-phase samples that were obtained from nine STARI patients from Missouri and from one patient with documented Borrelia lonestari infection who acquired this infection in either North Carolina or Maryland. All of these samples were C6 negative. Seventy acute- or convalescent-phase specimens from 63 STARI patients from Missouri were C6 tested at the second site. All but one of these STARI specimens were also negative. In contrast, of nine acute- and nine convalescent-phase serum specimens obtained from culture-confirmed Lyme disease patients with EM from New York state, seven were C6 positive at the acute stage, and eight were positive at convalescence. The C6 test is negative in patients with STARI, providing further evidence that B. burgdorferi is not the etiologic agent of this disease.

Antibodies, Bacterial↗

Polymorphonuclear cell function in the various polar types of leprosy and erythema nodosum leprosum.

Polymorphonuclear leukocyte motility, both in vivo and in vitro, and reduction of Nitro Blue Tetrazolium was studied in tuberculoid and lepromatous leprosy patients and a group of lepromatous patients with erythema nodosum leprosum (ENL). A profound defect in random migration, chemotaxis, and chemokinesis was found in lepromatous patients with and without complicating ENL, and marked depletion of skin window migration confirmed these in vitro findings. Tuberculoid patients exhibited a mild defect in polymorphonuclear leukocyte motility. Serum inhibitors of normal polymorphonuclear leukocyte chemotaxis were found in all types of leprosy, but sera from lepromatous and ENL patients were most inhibitory. Resting levels of Nitro Blue Tetrazolium reduction were normal in all three groups. Reconstitution of polymorphonuclear leukocyte cells from normal and ENL patients with ENL serum, however, showed increased Nitro Blue Tetrazolium reduction well above the normal range, whereas reconstitution with normal, lepromatous, and tuberculoid sera failed to increase Nitro Blue Tetrazolium reduction above the normal values.

Chemotaxis, Leukocyte↗

Experimental Lyme disease in rabbits: spirochetes found in erythema migrans and blood.

In attempts to produce experimental Lyme disease, 33 rabbits were inoculated with Lyme spirochetes by tick feeding or from tick organ homogenates or cultures. Two rabbits developed erythema chronicum migrans at the site of inoculation, in one instance 2 days after injection of a tick organ homogenate and in the other instance, 17 days after feeding of infected Ixodes dammini ticks. Spirochetes were seen in skin biopsy specimens of the second lesion with Warthin-Starry and immunoperoxidase stains. Spirochetes were also recovered from blood cultures of two additional rabbits 2 weeks post-inoculation. These findings are characteristic of early Lyme disease in humans and give additional support for the spirochetal etiology of Lyme disease.

Animals↗

Natural emergence of antigen-reactive T cells in lepromatous leprosy patients during erythema nodosum leprosum.

Fifteen lepromatous leprosy (LL) patients undergoing erythema nodosum leprosum (ENL) reactions were compared with 13 stable, uncomplicated, anergic individuals of the same leprosy background. ENL patients showed significant antigen-induced leukocyte migration inhibition (migration index = 0.058 +/- 0.01), paralleling the values obtained with a responder tuberculoid leprosy population (migration index = 0.04 +/- 0.004). Both phytohemagglutinin-induced general T-cell proliferation and, more significantly, antigen-induced lymphoproliferation were enhanced during the acute phase of the reaction. Suppressor cell activity, monitored by a costimulant assay, showed enhanced antigen-stimulated suppression of mitogen responses. Interestingly, the improvement in in vitro T-cell responses was not reflected in dermal reactivity, since 48-h delayed-type hypersensitivity responses after intradermal injection of soluble Mycobacterium leprae antigens continued to be poor. After subsidence of reactional lesions, leukocyte migration inhibition, lymphoproliferation, and suppressor cell activity were reduced to the unresponsive state seen in stable LL patients. Significantly, perturbations of T-cell reactivity are detectable in ENL reactions, indicating the natural but transient emergence of antigen-induced T cells in LL.

Antigens, Bacterial↗

Critical residues of the Mycobacterium leprae LSR recombinant protein discriminate clinical activity in erythema nodosum leprosum reactions.

We reported earlier (S. Singh, N. P. Shanker Narayan, P. J. Jenner, G. Ramu, M. J. Colston, H. K. Prasad, and I. Nath, Infect. Immun. 62:86-90, 1994) that polyclonal antibodies directed against selective sequences in the Mycobacterium leprae recombinant protein designated LSR were present in lepromatous leprosy patients undergoing erythema nodosum leprosum (ENL) reactions (type 2 reactions). In this study using peptides with single-residue deletions from positions 6 to 24, we define three distinct regions, GVTY, NAA, and RGD, which were important for antibody recognition and for the discrimination of clinically silent and active ENL reactions. Antibodies against NAA were found only in patients undergoing active reactions. This is in contrast to the results for the RGD motif, which was recognized in all ENL patients, irrespective of the clinical status. Though GVTY was recognized in both groups of patients, its recognition was masked by the flanking glutamic acid. These findings point towards a specific molecular recognition pattern that emerges when a lepromatous leprosy patient undergoes immune perturbations leading to ENL reactions. Moreover, the fine specificity of immunological recognition changes during the natural evolution of the host-parasite interaction.

Amino Acid Sequence↗

Inflammatory cytokine production predominates in early Lyme disease in patients with erythema migrans.

In a study of cytokine production ex vivo by Borrelia burgdorferi-stimulated peripheral blood mononuclear cells from 27 patients with culture-positive erythema migrans, production of inflammatory cytokines predominated, particularly gamma interferon and, to a lesser degree, tumor necrosis factor alpha. In contrast, with the exception of interleukin-13, anti-inflammatory cytokine production was negligible. Thus, B. burgdorferi antigens in early Lyme disease often induce a strong inflammatory response.

Antigens, Bacterial↗

Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions.

Current laboratory diagnosis of Lyme disease relies on tests for the detection of antibodies to Borrelia burgdorferi, the etiologic agent of the disease. These tests are often unreliable because of a lack of sensitivity and specificity and test-to-test variability. The purpose of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) amplification for detection of B. burgdorferi in skin biopsy specimens. Forty-six 2-mm skin biopsy samples were obtained from 44 patients with a clinical diagnosis of erythema migrans, 9 of whom were receiving antibiotic therapy at the time of biopsy. Specimens were ground in BSK medium with separate aliquots taken for culture and PCR. Of the specimens from the untreated group, 57% (21 of 37) were positive by culture and 22% (8 of 37) were culture negative; 22% (8 of 37) of the cultures were uninformative because of contamination. By comparison, 22 (59%) of 37 specimens were positive by PCR amplification. Of 21 culture-positive samples, 13 (62%) were also positive by PCR analysis. Thus, the sensitivity of the PCR was 59 to 62%, based on either a clinical or cultural diagnosis of untreated Lyme disease. None of the nine specimens from antibiotic-treated patients grew in culture, whereas two of the nine were positive by PCR analysis. Given the complexity and time required for culture, PCR is a promising technique for the diagnosis of early Lyme disease.

Base Sequence↗

Detection of Borrelia burgdorferi sensu lato in lesional skin of patients with erythema migrans and acrodermatitis chronica atrophicans by ospA-specific PCR.

The aim of this study was to develop a sensitive and specific PCR for the detection of Borrelia burgdorferi DNA. The plasmid-located gene coding for the outer surface protein A (OspA [31-kDa protein]) was used as a target. Nucleotide sequence information from different B. burgdorferi ospA genotypes was used to design primers homologous to different genotypes. The sensitivity of the nested PCR differed from 1 fg to 1 pg of borrelial DNA, depending on the strain analyzed. No cross-reactions with DNA from spirochetes other than B. burgdorferi or with human DNA were observed. A total of 22 skin biopsy samples from patients with erythema migrans (EM [n = 10]) or acrodermatitis chronica atrophicans (ACA [n = 12]) were examined for the presence of B. burgdorferi by nested PCR. Of 22 biopsies, 80% from EM patients and 92% from ACA patients were positive by PCR amplification. By comparison, 50% of the EM patients had elevated B. burgdorferi-specific immunoglobulin M (IgM) and/or IgG antibody levels as tested by enzyme-linked immunosorbent assay (ELISA) using purified B. burgdorferi flagella as antigen. A total of 33% of ACA patients had elevated IgM titers, and all had high IgG titers in their sera. Only 30% of specimens from patients with EM and none from patients with ACA were positive by culture. All culture-positive specimens were also positive by PCR. Thus, the sensitivities of the PCR were 80 and 92%, respectively, for patients with EM and ACA on the basis of the clinical and histopathological diagnoses of Lyme disease. From these results, we conclude that PCR is a suitable method to detect B. burdorferi sensu lato DNA in skin biopsy samples and could be applied as an additional diagnostic tool.

Acrodermatitis↗