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[Lymphocyte proliferation test in cutaneous manifestations of Lyme borreliosis].

The humoral immunoreactivity in Lyme borreliosis is a well characterized parameter for establishing the diagnosis of a Borrelia burgdorferi (Bb) infection. Since patients with seronegative Lyme borreliosis have been described, lymphocyte proliferation tests may be used for detecting patients who only develop a cellular immunoreactivity against Bb organisms. We performed a the lymphocyte proliferation assays in order to determine the cellular immunoreactivity to these spirochetes in given patients with histologically confirmed diagnosis of erythema migrans (EM), acrodermatitis chronica atrophicans (ACA), and for control purposes patients with Lyme disease non associated dermatoses (NLDH) and healthy volunteers (G). Stimulation index was defined as 3H thymidine-uptake in peripheral mononuclear cells, calculated as quotient dpm (stimulated cells)/dpm (unstimulated cells) (dpm = disintegrations per minute). Stimulation indices > 10 were considered positive. We detected elevated cellular immunoreactivity of peripheral mononuclear cells in 33% EM-patients (3/9) and in 23% (3/13) ACA patients tested. Patients tested before and after antibiotic therapy showed a significant decrease of stimulation index after antimicrobial treatment (p < 0.05). Patients the EM, who are mostly seronegative at the onset of cutaneous eruption exhibit in a third of patients an elevated cellular immune response to Bb. Therefore lymphocyte proliferation assays can be recommended as an additional test system in case of lack of serological response. The significant decrease of stimulation index after antimicrobial therapy indicates for downregulation of the cellular immune response to these spirochetes investigated, and counts for the specificity of this test system.

Acrodermatitis↗

[The dermatologic spectrum of Lyme borreliosis].

The classical symptoms of Lyme borreliosis (LB) on the skin, erythema migrans, borrelia lymphocytoma and acrodermatitis chronica atrophicans (ACA) can be diagnosed clinically. In atypical cases, however, the diagnosis of a Borrelia burgdorferi (Bb) infection is based on the isolation of this bacterium from affected tissues. In early Lyme disease problems are arising in complicated erythema migrans which may represent reinfection, or with a failure of antibiotic treatment in some patients. The pathological changes in ACA presumably result from a chronic T-cell-mediated tissue injury with atrophy or sclerosis of connective tissue. On the other hand the presence of numerous plasma cells indicates activation of the humoral immune system where a progression into a malignant B-cell lymphoma is possible. In the recent past Bb could be cultivated from skin biopsies of a series of dermatoses of unknown origin, such as circumscribed scleroderma, dermatomyositis-like syndrome, relapsing nodular panniculitis, granuloma anulare and roseolar erythemas. New therapeutic strategies by administering antibiotics have been found to be effective in the described Bb induced dermatoses. Future studies should be focused on new standardized diagnostic procedures which make it possible to define the spectrum of dermatoses associated with a Bb infection.

Acrodermatitis↗

Unusual musculoskeletal manifestations of Lyme disease.

We report on the imaging features of musculoskeletal abnormalities in a 52-year-old woman suffering from Lyme disease presenting with acrodermatitis chronica atrophicans (ACA). The patient developed recurrent attacks of migratory asymmetrical oligoarthritis, involving articular and peri-articular structures, including the metatarsophalageal (MTP) joints, scapular bone, thoracic spine, elbow, gluteal area, knee, ankle and metacarpophalangeal (MCP) joints. Six months after the first symptoms, Magnetic Resonance Imaging (MRI) showed bone marrow oedema within the proximal phalanx of the right fifth toe, adjacent to an ACA rash. A year after the onset of the disease, swelling at the right scapular region occurred, and MRI showed osseous, periosteal and soft tissue involvement of the superior margin of the right scapula and adjacent rib. On MRI of the spine, there was bone marrow infiltration with irregular delineation of the anterior corner of the thoracic vertebrae 4 to 6, corresponding to an osteoblastic bony lesion on radiographic examination. This case report is unique, because MRI documentation of bony abnormalities and periarticular soft tissue swelling, accompanying an attack of ACA has never been reported previously. Moreover, involvement of the osseous spine and the scapular bone have never been described in the radiological literature.

Acrodermatitis↗

Antibiotic therapy in early erythema migrans disease and related disorders.

Between December 1978 and July 1985, we used various antibiotics for the treatment of 97 adult patients with early erythema migrans disease (EMD). Six patients with borrelial lymphocytoma (BL) and 20 with acrodermatitis chronica atrophicans (ACA) were treated similarly. Follow-up was for a median of 20, 14, and 12 months, respectively. The erythema migrans and all associated symptoms resolved within a median of 3 weeks (0.5-18.4), BL within 7 weeks (4-16), and ACA partly or completely within several months. A Jarisch-Herxheimer (-like) reaction was observed in 8 patients with EMD. Fourteen patients with EMD and one with ACA developed an exacerbation of symptoms or new manifestations between the 2nd and 20th day, and 28 patients with EMD and one with ACA continued to have or acquired various symptoms greater than or equal to 3 weeks after initiation of therapy. Arthralgia, neurologic and constitutional symptoms, and in one instance a slight pulmonary interstitial edema developed in EMD. More severe initial illness was a risk factor for the development of later symptoms in EMD. Retreatment was more often necessary in ACA than in EMD. A patient with ACA had a recurrence after 5 1/2 years. IgG antibody titers rose at least fourfold in 5 patients with ACA and in 1 with EMD despite therapy. We tentatively recommend minocycline or high doses of parenteral penicillin for the treatment of these disorders.

Acrodermatitis↗

Epidemiology of borrelia infections in Austria.

From April 1984 to July 1985 873 cases of Borrelia infections were registered at the Hygiene Institute of the University of Vienna. 2609 serum samples of these patients were investigated for antibodies against B. burgdorferi by means of IFA- and ELISA-tests. Erythema chronicum migrans (ECM) was recognized in 60.9% of patients, neurological abnormalities were recorded in 23.4% of which the majority manifested themselves as polyradiculitis and meningopolyneuritis (MPN). Acrodermatitis chronica atrophicans (ACA) was recognized in 11.5%. A small number of patients suffered from Lymphadenosis cutis benigna (LCB), arthritis and cardiac abnormalities. Sixty percent of patients were females and 40% males. Infections were found in all age groups ranging from 2-83 years in females and 1-85 years in males. Tick- or insect-bites prior to the onset of illness were reported by 47.2% and 15.6% of patients, respectively. The main vector is the hard tick Ixodes ricinus. Flying insects from the family tabanidae, i.e. Chrysops caecutiens and Haematopota species, must also be considered as transmitters. Antibodies to B. burgdorferi were found in 22.3%, 93.6% and 100% of sera from patients with ECM, MPN and ACA, respectively. Six of 11 patients with LCB and all with arthritis and cardiac abnormalities showed serologic reactivity. Geographically, Borrelia infections are distributed in all states of Austria. The seasonal distribution of cases show a peak in July and August, but the onset of clinical manifestation could be observed throughout the year. These results present Austria as an area where tick- or insect-borne Borrelia infections are very frequent and endemic in all Austrian states.

Acrodermatitis↗

Downregulation of class II molecules on epidermal Langerhans cells in Lyme borreliosis.

BACKGROUND: Borrelia burgdorferi can be isolated from the skin of patients with acrodermatitis chronica atrophicans (ACA), a late-stage manifestation of Lyme borreliosis; despite a marked T-cell infiltrate in lesional skin and high antibody titres in patients' sera. OBJECTIVES: To determine whether antigen-presenting Langerhans cells (LCs), which reportedly show signs of injury in erythema chronicum migrans (ECM), the early stage of disease, are altered in ACA. PATIENTS/METHODS: We studied the immunophenotype of cutaneous leucocytes on cryostat sections of lesional skin from both ECM and ACA patients. RESULTS: The total number of CD1a+ cells evaluated by semiautomatic image analysis was lower in ECM (594 +/- 263 cells mm(-2) epidermis) than in ACA (835 +/- 317 cells mm(-2) epidermis). HLA-DR expression was remarkably downregulated on CD1a+ LCs to 29% in ECM and 18% in ACA, whereas in normal skin, most of the epidermal CD1a+ dendritic cells were HLA-DR+. The inflammatory infiltrate was mainly composed of CD68+ macrophages and CD45RO+ memory T cells, with a predominance of CD4+ helper T cells. CONCLUSIONS: It is conceivable that the downregulation of major histocompatibility complex class II molecules on LC in both the early and late skin manifestations of Lyme borreliosis is indicative of a poorly effective anti-B. burgdorferi immune response and thus at least partly responsible for the insufficient elimination of this micro-organism from ACA skin.

Acrodermatitis↗

Clinical features of early erythema migrans disease and related disorders.

104 patients with erythema migrans disease (EMD), 7 patients with borrelia lymphocytoma (BL), and 21 patients with acrodermatitis chronica atrophicans (ACA) were prospectively followed for a median of 20, 14, and 12 months, respectively. 99 patients with EMD and 6 with BL were treated with antibiotics early for their illness. 72 patients with EMD had 1 to 10 constitutional symptoms besides the erythema migrans, 32 had erythema migrans alone, and a child with BL had urticaria. Out of 39 patients with EMD, 23 acquired arthralgia, 18 signs and symptoms consistent with neurologic manifestations and 8 with cardiac involvement before or after therapy. 4 patients with EMD and 1 with BL had up to 10 multiple erythema migrans lesions. 3 patients with EMD experienced a reinfection and 1 with ACA a relapse. Several patients with ACA developed signs and symptoms consistent with neurologic, cardiac and joint involvement, and 2 had a history of EMD. Elevated antibody titers against Borrelia burgdorferi were present in 48% of 69 patients with EMD, 5 with BL and 11 with ACA, and in 93% of another group with EMD, 2 with BL and 10 with ACA, when tested against other borreliae. Increased values of the ESR, IgG, IgA and IgM were found in more patients with ACA than with EMD. The median of IgA and IgM was significantly higher in ACA than in EMD. Borreliae were found in brain and liver of a newborn. Early EMD appears to be quite similar to early Lyme disease.

Acrodermatitis↗

[Borrelia infections of the skin--progress of knowledge since the discovery of Lyme disease].

The description of Lyme disease in 1976 and the detection of its causative agent, the spirochete Borrelia burgdorferi (B. burgdorferi), in 1982 led to an increase in our knowledge of the course of B. burgdorferi infection and its clinical manifestations. The classic tick-borne dermatoses erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LABC) and acrodermatitis chronica atrophicans (ACA) were proven by isolation of the spirochete from skin lesions to be caused by B. burgdorferi infection. In early disease (less than 1 year) ECM and LABC can develop locally at the site of infection (stage I), but both these skin manifestations can also occur together with multiple lesions after dissemination of the causative organism (stage II). ACA is typical for late infection (greater than 1 year, stage III). High titres of B. burgdorferi antibodies have been found in patients with localized sclerodermalike lesions (circumscribed scleroderma, lichen sclerosus et atrophicus, anetoderma), and frequent simultaneous occurrence of ACA suggests an association with late B. burgdorferi infection. Similarly, we found four cases of cutaneous B-cell lymphoma possibly arising from LABC in association with the same markers of late B. burgdorferi infection. Additionally, some cases of Schönlein-Henoch purpura and of Shulman syndrome may be associated with Lyme borreliosis. The disease is endemic in central Europe, and almost exclusively ticks of the Ixodes ricinus complex seem to transmit B. burgdorferi to humans, whereas the reservoir of infection seem to be rodents, especially mice. The main diagnostic tool is serological examination for B. burgdorferi antibodies, which will become detectable 3-6 weeks after infection. Enzyme-linked immunosorbent assay (ELISA) and the indirect immunofluorescence test (IFT) revealed similar sensitivity. In early disease, sensitivity for antibody detection could be improved by immunoblot technique and by flagellum-ELISA, which is specific for this early sensitizing B. burgdorferi antigen. For treatments, penicillin is no longer recommended as the drug of first choice, because low sensitivity of B. burgdorferi has been observed in vitro and in vivo. Tetracycline, doxycycline and amoxicillin p.o. are now preferred for the treatment of Lyme borreliosis, and in neurologic and cardiac abnormalities ceftriaxone i.v. is recommended. Treatment duration should be 14 days in early disease and 30 days in late disease.

Acrodermatitis↗

Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding?

BACKGROUND: The historical association of acrodermatitis chronica atrophicans (ACA), now known to be a late manifestation of Lyme disease caused by Borrelia afzelii, with cutaneous lymphoma, and several small series of PCBCL with positive Lyme disease borrelial serology initiated a study of this association. Material and methods In the last 9 years, 30 patients with PCBCL have been observed and followed, 22 of them were tested for borrelial serology. The control group consisted of 85 patients with NHL (10 cutaneous T-cell, 25 extranodal B-cell non-PCBCL, 50 nodal B-cell), 30 patients with breast cancer and 60 blood donors. The screening tests were two different ELISA tests for B. burgdorferi sensu lato and sensu stricto, and reactive sera were further tested with the ELISA test for B. garinii, a Western blot (WB) test for Swiss Borrelia strains and a WB test for Bavarian Borrelia strains, since an immunoblot made with local strains was not available. Studies with a differential WB test for B. burgdorferi sensu stricto, B. garinii and B. afzelii was performed afterwards, as well as serological studies ruling out cross-reactions with Leptospiras and Treponema. RESULTS: Fifteen of 22 patients with PCBCL were positive on the screening tests, three of them falsely. Thus, the incidence of positive borrelial serology was 12/22 (55 per cent) in the PCBCL group. No positives were detected in the cutaneous T-cell lymphoma group; 2/25 patients (8 per cent) were positive in the extranodal B-cell NHL group (the localizations being vestibulum nasi and oral cavity), 2/50 (4 per cent) were positive in the nodal B-cell NHL group, 2/30 (7 per cent) in the breast cancer group and 2/60 (3 per cent) in the blood donor group. The cumulative incidence in the control groups was 8/175 (4,6 per cent). The incidence was significantly higher in PCBCL patients as compared to each of the control groups, p value ranging from 0.004 to <0.0001. Two positive patients had ACA, one arthritis. Borrelia afzelii was most often implied for positive serology in the differential WB. No cross-reactions with Treponema and the Leptospiras were documented. CONCLUSION: In conclusion there appears to be a clustering of positive serology for Lyme disease Borrelias in PCBCL patients possibly related to an ethiopathogenic relationship. Mechanisms of Borrelia escape from immunosurveillance mechanisms, persistence of both their mitogenic and antigenic stimuli for B-cells, and SALT formation may be involved in the pathogenesis of a subset of PCBCL.

Acrodermatitis↗

Ultrastructure of Borrelia burgdorferi in tissues of patients with Lyme disease.

Spirochetal organisms were sought in 18 skin and 4 synovial membrane specimens obtained by biopsy from 22 Lyme disease patients. The presence of spirochetes in body tissues was histologically demonstrated in one patient with lymphadenosis benigna cutis, one patient with acrodermatitis chronica atrophicans and in one patient with active arthritis. The organisms were 5-30 microns long and 0.12-0.25 microns thick, had 8 or 11 flagella arising from both ends of the body, and their ultrastructure was analogous to that of cultured Borrelia burgdorferi strains. They were located intra- or perivascularly, or in the collagenous connective tissue of the skin and synovium. This implies that Lyme spirochetes may have a potential to survive in body tissues and cause injury to blood vessels.

Antibodies, Bacterial↗

Frequencies of Borrelia burgdorferi-reactive T lymphocytes in Lyme arthritis.

Using a limiting dilution system, frequencies of Borrelia burgdorferi-reactive T cells were determined in the blood and synovial fluid of four patients with chronic Lyme arthritis (LA), one patient with acrodermatitis chronica atrophicans (ACA), two patients with other inflammatory joint diseases, and two healthy individuals. B. burgdorferi-reactive precursor T cells ranged from 1/750 to 1/8220 in case of LA and ACA patients and from 1/820 to 1/31 400 in case of controls. In vivo activated B. burgdorferi-reactive T cells were almost absent in control subjects. With one exception, they were detected in LA patients at frequencies ranging from 1/1 300 to 1/15 400. Interestingly, even after successful antibiotic therapy of LA patients, similar frequencies of in vivo activated B. burgdorferi-reactive T cells were observed in the peripheral blood, provided that low cell concentrations were used for culture. At higher cell numbers, the fraction of B. burgdorferi-reactive T cells apparently dropped, suggesting regulatory phenomena.

Adult↗

Recombinant immunoblot in the serodiagnosis of Lyme borreliosis. Comparison with indirect immunofluorescence and enzyme-linked immunosorbent assay.

A recombinant immunoblot was developed for detection of IgM and IgG antibodies in patients with Lyme borreliosis. The recombinant antigens were the chromosomal-encoded Borrelia burgdorferi proteins p100, the flagellin and an internal flagellin fragment thereof as well as the plasmid-encoded outer surface proteins A (OspA) and C (OspC). A panel of 144 sera from patients with Lyme borreliosis (erythema migrans, n = 31; neuroborreliosis state II, n = 60; Lyme arthritis, n = 24 and acrodermatitis chronica atrophicans, n = 19) have been investigated and the results have been compared to the immunofluorescence absorption test (IFA-ABS) and to two different enzyme-linked immunosorbent assays [the flagellin ELISA and a newly developed ELISA (OGP-ELISA)]. The two ELISAs were comparable in sensitivity, whereas the IFA-ABS was less sensitive for IgM antibody but equally sensitive for IgG antibody detection. Immunoblot analysis revealed that IgG antibodies are mainly reactive with p100 and the internal flagellin fragment (sensitivity 51% and 32%, respectively) and rarely with OspC (14%). All patients with late Lyme borreliosis had IgG antibodies against the p100. IgM antibodies were predominantly directed against OspC (43%) and in a lower extent against the internal flagellin fragment and p100 (15% and 13%, respectively). The complete flagellin was not useful due to a high number of unspecific reactions with control sera and the OspA was only exceptionally reactive in Lyme borreliosis patients. The sensitivity of IgM antibody detection could be increased in cases with early Lyme borreliosis from 46% to 65% when the OspC blot was performed in addition to the flagellin ELISA, or from 56% to 65% when performed in addition to the OGP-ELISA. The recombinant blot is, therefore, a valuable diagnostic test to increase sensitivity of early antibody detection and is regarded as a valuable confirmatory test also in late disease.

Antibodies, Bacterial↗

Lyme borreliosis: ten years after discovery of the etiologic agent, Borrelia burgdorferi.

Since the recovery of its causative agent, Borrelia burgdorferi, in 1981, Lyme borreliosis has become the most prevalent tick-borne disease in the United States as well as in Europe. Its steadily increasing clinical spectrum now includes erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis beniga cutis, arthritis, myocarditis, progressive meningoencephalitis, myositis, and various ocular and skin disorders. The true incidence of Lyme borreliosis in the world is unknown. In the United States, it has increased from 2,000 cases in 1987, to more than 8,000 in 1989. It occurs now in regions where the tick vectors, Ixodes dammini and Ixodes pacificus, are absent and where other species of ticks may be responsible for maintaining and distributing the spirochete. In Europe, Lyme borreliosis has been reported from 19 countries; its occurrence coincides with the distribution of the vector tick, Ixodes ricinus and possibly Ixodes hexagonus. Specific and dependable serological tests are still not available, but development of probes for specific antigens and the polymerase chain reaction appear promising in detecting ongoing infections and in identifying B. burgdorferi in ticks, animal, and human hosts. Brief reference is made to advances in the preparation of whole cell and genetically engineered vaccines.

Animals↗

Western blot analysis of sera from Lyme borreliosis patients according to the genomic species of the Borrelia strains used as antigens.

Sera of 52 Lyme borreliosis patients classified according to their clinical features were analysed by Western blot using as antigens Borrelia strains belonging to three recently described genomic species. The antibody response was demonstrated to be homologous within each genospecies. Serum reactivity was studied for each of the type strains Borrelia burgdorferi sensu stricto (strain B31T), Borrelia garinii (strain 20047T) and group VS461. Seven of 15 sera (46.6%) of patients with meningoradiculitis showed preferential reactivity with Borrelia garinii (strain 20047T), all of 8 sera (100%) of patients with acrodermatitis chronica atrophicans showed preferential reactivity with group VS461 (strain VS461) and 8 of 16 sera (50%) of patients with arthritis showed preferential reactivity with Borrelia burgdorferi sensu stricto (strain B31T). The presence of a strong response to OspA and OspB proteins of Borrelia burgdorferi sensu stricto was found only in this last group of patients. These results suggest that there are clinical implications of the recently described modifications in the taxonomy of Borrelia burgdorferi.

Antibodies, Bacterial↗

Childhood Lyme borreliosis in Europe.

Lyme borreliosis is a multisystem disorder common in childhood. It is an acute and persistent anthropozoonotic infection caused by the spirochete Borrelia burgdorferi (Bb) which is transmitted by Ixodes ticks. After the tick bite in summer, erythema migrans, meningoradiculoneuritis, or carditis may develop within the same season. Later manifestations may be oligo-arthritis, progressive encephalomyelitis, or acrodermatitis chronica atrophicans. The most common course is probably asymptomatic. Connatal infection is possible. Diagnosis is established mainly by history and clinical manifestations. The antibody response to Bb can be measured in serum and cerebrospinal fluid. Tests may be false-negative early in the course of the disease or after early treatment. False-positive results may be caused by cross-reactions. Interpretation of test results must also consider unrelated anamnestic titres or asymptomatic infection. Treatment with appropriate antibiotics cures the disease in most patients, however some patients may not respond. The optimal drug has not yet been found. Best prophylaxis is by early removal of the tick from the skin.

Animals↗

Clinical and epidemiological features of Lyme borreliosis in Bulgaria.

INTRODUCTION: Data on disease expression and epidemiological characteristics of Lyme borreliosis in south-eastern Europe are scarce. PATIENTS: To reveal features of Lyme borreliosis in Bulgaria, clinical data and epidemiological characteristics of 1257 patients reported between 1999 and 2002 were analysed. RESULTS: The most affected age group was 5-9 years, followed by 45-49 years, 50-54 years, and 10-14 years. Most of the patients (68%) lived in a rural area or were attacked by ticks during activities in a rural area. Lyme borreliosis cases occurred throughout the year with two peaks--one in June and second smaller one in September. The most common clinical manifestation was erythema migrans (EM), diagnosed in 868 (69.1%) of the patients. Rashes had a median diameter of 11 cm and were predominantly located on lower extremities. Forty-four per cent of the rashes consisted of homogenous erythema and 56% had central clearing. Multiple EM was detected in 4.3% of the EM cases. Neuroborreliosis was the second most common presentation of Lyme borreliosis, diagnosed in 19% of the patients. Lyme arthritis was found in 8% of the patients. Heart and ocular manifestations were recorded in 1.1% and 0.9% of the patients, respectively. Borrelial lymphocytoma and acrodermatitis chronica atrophicans were very rare (0.3%). Twenty-seven patients (2.1%) had multiple organ involvement. CONCLUSIONS: The results of the study show that the epidemiology and clinical manifestations of Lyme borreliosis in Bulgaria are similar to those in the majority European countries but possess some distinguishing characteristics.

Adolescent↗

[Lyme borreliosis. Cutaneous manifestation].

Lyme borreliosis is a tick transmitted infectious disease caused by different genospecies of Borrelia burgdorferi sensu lato. In USA only one species B. burgdorferi sensu stricto is prevalent, whereas in Europe at least 5 different pathogenic species could be identified. The most prevalent species are B. afzelii and B. garinii. Infection is not always causing disease. In early infection, a localized skin inflammation, called erythema migrans, occurs around the tick bite, hematogenous dissemination of Borrelia causes flu like symptoms up to meningitis and multiple erythemata migrantia on the skin. In late stage multiple organ systems can be affected, in Europe especially the skin with various forms of acrodermatitis chronica atrophicans, the central and peripheral nervous system, joints and heartmuscle. Lyme borreliosis can be diagnosed by the typical history, the clinical symptoms and the elevated Borrelia specific IgM- and IgG-antibodies in serum and CSF according to the MIQ guidelines, in special cases B. burgdorferi can be cultivated or DNA detected by PCR. Therapy of choice for early infection is oral antibiotics like doxycycline, amoxicillin and cefuroxime for at least 10 days up to 21 days. Late stage infections should be treated for 3-4 weeks. Patients with neurological symptoms should be treated intravenously with ceftriaxone or penicillin G.

Borrelia burgdorferi↗

[Ten clues to the histopathologic diagnosis of infectious skin diseases].

Specific diagnoses of infectious skin diseases can be established in dermatopathology by several methods: by algorithms based on pattern analysis, by differential diagnosis of clinicopathologically similar disorders, by attention to pitfalls, by exceptions to the rules and finally, very elegantly by clues. Ten clues to specific diagnoses of infectious skin diseases which are of importance in routine practice are presented. Clue 1: Features of an angiocentric angiodestructive lymphoma in the centre of a wedge-shaped necrotic insect bite reaction are a clue to a bite by a spider. Clue 2: Parakeratosis with spiky imprints on the surface above features of an insect bite reaction are a clue to scabies. Clue 3: A faintly eosinophilic section of a skin specimen with prominent fibrin thrombi and extravasated erythrocytes are a clue to a septic fungal vasculitis. Clue 4: Infectious agents in association with otherwise typical features of leukocytoclastic vasculitis are a clue to septic vasculitis. Clue 5: Steel-grey nuclei with marginated nucleoplasm of keratinocytes are a clue to the diagnosis of early infection by herpes virus. Clue 6: Owleye-like cells are a clue to infection by cytomegalovirus. Clue 7: Detection of Entamoeba histolytica in perianal and perineal ulcers are a clue to amebiasis. Clue 8: Round-oval to rectangular spaces within the stratum spinosum of the epidermis are a clue to larva migrans. Clue 9: Macrophages and plasma cells in association with otherwise typical features of pityriasis lichenoides are a clue to secondary syphilis. Clue 10: A lichenoid infiltrate of lymphocytes and plasma cells are a clue to acrodermatitis chronica atrophicans.

Animals↗