Peripheral Nerve Involvement in Cutaneous Leishmaniasis (Old World)

A review of 288 skin biopsy specimens from cutaneous leishmaniasis lesions caused by Leishmania major showed assorted nerve changes in 14 biopsy specimens (5%). Ten patients had perineural inflammatory cell infiltrate consisting of either lymphocytes or a mixture of lymphocytes, plasma cells, and macrophages. Four patients had inflammatory cell invasion of the nerves (neuritis), and in one of them the inflammation was granulomatous and associated with nerve destruction. Amastigotes were seen inside the nerves in two patients. Sensory testing of 50 consecutive patients with cutaneous leishmaniasis identified two patients with diminished sensations over the lesions.     

Efficacy of local heat therapy by radiofrequency in the treatment of cutaneous leishmaniasis, compared with intralesional injection of meglumine antimoniate

BACKGROUND: Cutaneous leishmaniasis (CL) is a serious public health problem in many tropical and subtropical regions of the world. Treatment of CL can prevent disfiguring scars. AIM: The efficacy of local heat therapy by radiofrequency (RF) was compared with intralesional injection of meglumine antimoniate in the treatment of CL. METHODS: This was a randomized clinical trial. Patients with antroponotic cutaneous leishmaniasis (ACL) in the Isfahan province of Iran were enrolled in the study if the examination of a smear from a suspected CL lesion was confirmed positive for Leishmania. Patients were randomly allocated to one of two treatment groups. Group A was treated by heat therapy by RF at 50 degrees C for 30 s once weekly for 4 weeks, and group B was treated with intralesional injection of meglumine antimoniate once weekly for 4 weeks. Follow-up lasted 6 months. Response to treatment was classified as complete (lesions flattened, no induration, and epidermal creases had appeared), partial (reduction in lesion size, but without the appearance of epidermal creases) and poor (no reduction in lesion size). RESULTS: Of 117 participants, 57 patients with 83 lesions in group A and 60 patients with 94 lesions in group B completed the study and were followed up for 6 months. Complete, partial and poor response to treatment were 80.7%, 12% and 7.3% in group A, and 55.3%, 21.27% and 23.40% in group B, respectively (P = 0.001). In both groups, there was no relapse in patients with complete response after 6 months of follow-up. CONCLUSIONS: Heat therapy with thermogenerator RF can be used as an efficacious treatment in the lesions of CL. It is more effective than the conventional treatment with intralesional meglumine antimoniate injection.     

Immunohistochemical analysis of sensory nerves and neuropeptides,and their contacts with mast cells in developing and mature psoriatic lesions

The distribution of the neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP) was studied immunohistochemically in psoriatic skin during the Koebner response (6 h, 2 days, 7 days, 14 days, 21 days), and in mature psoriatic plaques, of 37 psoriatic patients. The morphological association of sensory nerves, SP and VIP with papillary mast cells was also monitored. The nerves containing SP, VIP or CGRP were very scanty in control skin, and in non-lesional and Koebner-negative psoriatic skin. The first psoriatic lesions were seen 7 days after tape stripping the symptomless psoriatic skin. SP- and VIP-containing nerves were slightly increased in Koebner-positive specimens, but the increase was very prominent in dermal papillae of mature psoriatic plaques. In the plaques, nerve-mast cell contacts were significantly increased (p<0.001) compared with non-lesional psoriatic skin. Only SP-positive fibres were detected in the epidermis and in contact with papillary mast cells. VIP was mainly located around capillaries where SP was also found. No change was noted in CGRP-positive fibres between lesional and non-lesional specimens. The appearance of SP and VIP in the capillary walls is morphological evidence for their function as vasodilators in psoriatic lesion. A slight increase in SP- and VIP-positive fibres in Koebner-positive specimens suggests that these neuropeptides may participate in the inflammatory reaction at an early stage. Their prominence in mature psoriatic plaques in turn indicates a role for them in the maintenance of psoriatic lesions. Morphological contacts between mast cells and SP-containing nerves give further evidence to the view that SP is capable of amplifying the inflammatory reaction also through the axon-reflex mechanism.Part of this work was presented at the meeting of the European Society for Dermatological Research, London, UK, 4–7 April 1992     

Diagnostic approach and significance of inducible nitric oxide positivity in human cutaneous leishmaniasis caused by leishmania tropica

AIM: To determine the usefulness of polymerase chain reaction (PCR) in the diagnosis of leishmaniasis and to emphasize the importance of inducible nitric oxide (iNOS). MATERIALS AND METHODS: Twenty-nine patients with cutaneous leishmaniasis diagnosed according to clinical criteria who live in rural areas of Antakya-Hatay/Turkey were included in this study. Twenty-five patients free of leishmaniasis were accepted as a control group. Punch biopsies and smears were obtained from lesions of the patients in the study group. Half of each punch biopsy specimen was processed in routine tissue processing. After routine tissue processing hematoxylin-eosin and iNOS immunohistochemical staining were applied. The remaining half of the biopsy specimens was studied by PCR method. INOS-positive stained macrophages were determined. RESULTS: The positive detection rates in 29 cases of cutaneous leishmaniasis (CL) were 96.5% by PCR, 86.2% by direct microscopic evaluation of biopsy and 58.6% by direct visualization of smear in this study. iNOS reaction was mildly positive in three cases, moderately positive in six cases and strongly positive in 20 cases. CONCLUSION: iNOS yielded positive reaction in all cases but this positivity showed differences with respect to the age of the lesions or the effect of iNOS on the immune mechanism. This reveals an inverse correlation between iNOS reactivity and duration of lesion (Spearman correlation r = -0.53, P = 0.003). There was no correlation between iNOS reactivity and patient age (Spearman correlation: r = 0.13, P = 0.5). In terms of gender, there was no association with iNOS.     

Lyme disease is a spirochetosis. A review of the disease and evidence for its cause

Fourteen patients with Lyme disease showed typical clinical features of erythema chronicum migrans. Eighteen biopsy specimens in all were obtained from the cutaneous lesions of these patients. The predominant histologic finding was a superficial and deep perivascular and interstitial infiltrate composed mostly of lymphocytes, or lymphocytes and either plasma cells and eosinophils or both. The plasma cells were found most frequently in biopsy specimens taken from the peripheries of the lesions, whereas eosinophils were found mostly in the centers of lesions. With the Warthin-Starry silver stain, spirochetes were found mostly at the borders of the lesions an in biopsy specimens containing plasma cells. Spirochetes were subsequently cultured from a typical skin lesion of erythema chronicum migrans. These findings corroborate previous indirect evidence that a spirochete might be the cause of Lyme disease.     

Congenital pauci-melanotic cellular blue nevus

Unusual or atypical melanocytic nevi can be confused with malignant melanoma. Two patients are presented here with a rare variant of melanocytic nevus. Both were men. One was 39 years old and sought medical attention after trauma of a "congenital mole". The other was 24 years old and presented with a history of a slowly growing lesion, which had been known since childhood. In both patients, the lesion occurred on the buttock. They were dermal and superficial subcutaneous nodules measuring 1.5 and 2.3 cm in greatest dimension, respectively. The tumors were composed of densely cellular fascicles of melanocytes arranged in a lobulated growth pattern. Rare nests of small epithelioid melanocytes were also seen. No melanin pigment was seen on hematoxylin and eosin-stained sections. Focal minimal pigment was noted by Fontana-Masson stain in one case. Involvement of numerous peripheral nerve trunks by fusiform melanocytes was a prominent feature. Rare mitotic figures were seen in melanocytes [1-2 mitoses per 50 high-power fields (HPF)]. The MIB-1 labeling index was low (less than 5% of the lesional cell population was immunopositive). Both tumors were excised with negative surgical margins. One patient underwent sentinel lymph node biopsy because there was controversy regarding the biologic potential of the lesion. No melanocytic tumor deposits were found in the lymph nodes. On clinical follow up of 11 years and 18 months after complete excision, both patients are alive and well with no evidence of recurrence. We regard these lesions as congenital monophasic and pauci-melanotic variants of cellular blue nevus. The nevi are presented here to enhance our knowledge of the morphologic spectrum of melanocytic tumors and to help avoid confusion with malignant melanoma.     

Oral hairy leukoplakia. A distinctive marker of human T-cell lymphotropic virus type III (HTLV-III) infection

Oral hairy leukoplakia (HL) is a newly described lesion occurring principally on the lateral borders of the tongue in immunosuppressed homosexual men infected with human T-cell lymphotropic virus type III (HTLV-III). Clinically, HL appears as a slightly raised, poorly demarcated lesion with a corrugated or "hairy" surface. Histologically, the lesion is characterized by keratin projections on the surface (which often resemble hairs), parakeratosis, and acanthosis. In addition, large pale-staining cells with pyknotic nuclei are seen in the upper stratum malpighii, which appear similar to the koilocytes described in uterine condylomata. Candida organisms are frequently observed on the lesion surface. Little, if any, subepithelial inflammation is present. Human papillomavirus and Epstein-Barr virus have been identified in biopsy specimens from lesions of oral HL. The association of this lesion in patients with HTLV-III infection has been established. We saw a patient with HTLV-III infection and HL, in whom the immunochemical and ultrastructural findings revealed the presence of a mixed viral infection. Because oral HL may be of diagnostic value as an early indicator of HTLV-III infection, awareness of its characteristic clinical, histologic, immunochemical, and ultrastructural features is important.     

Monoclonal antibody studies in the skin lesions of patients with anetoderma

In all five patients studied, monoclonal antibody studies of cryostat sections of skin biopsy specimens of anetoderma lesions revealed inflammatory cells reacting with anti-Leu-1, pan-T-cell antibody, and anti-Leu-3a, the helper/inducer T-cell antibody. Small numbers of suppressor cells were present in only three biopsy specimens. Four specimens showed OKM1, antibody-reacting cells (monocytes). The age of the lesion was not correlated with inflammation or the T-cell subsets identified.     

In vivo confocal scanning laser microscopy of a series of congenital melanocytic nevi suggestive of having developed malignant melanoma

OBJECTIVE: To determine the utility of confocal scanning laser microscopy (CSLM) in the in vivo evaluation of congenital melanocytic nevi (CMNs) that are suggestive of having developed melanoma. DESIGN: The CMNs suggestive of melanoma by clinical and dermoscopic examination were imaged by CSLM, and the findings correlated with the features seen on dermoscopic and histologic examination. SETTING: Dermatology clinic specializing in pigmented lesions. PATIENTS: Seven patients with clinically irregular small to medium CMNs. INTERVENTIONS: The areas imaged by CSLM were sampled with 3-mm punch biopsy specimens. The entire lesion was subsequently excised. The punch biopsy specimens were step sectioned horizontally to correlate with the CSLM images. Excised samples were step sectioned and processed routinely. Histologic features observed on CSLM were correlated with the features seen on dermoscopic and light microscopic examination. MAIN OUTCOME MEASURE: Correlation of the structures seen using CSLM with the dermoscopic and histologic features of CMNs and melanoma. RESULTS: The CSLM illustrated histologic characteristics of CMNs, including the presence of hyperpigmented keratinocytes, nevus cells, melanophages, and a normal "honeycomb" epidermal architecture. Features suggestive of melanoma were not evident by CSLM in 6 histologically proven benign CMNs. Histologic features associated with melanoma, such as an increased number of intraepidermal atypical melanocytes (pagetoid) and loss of normal epidermal cellular architecture, were identified by CSLM in 1 lesion, which on histologic analysis revealed melanoma in association with a CMN. CONCLUSION: Our results illustrate that CSLM may be useful for clinicopathologic correlations and for the preliminary noninvasive diagnosis of pigmented neoplasms in vivo.     

Early leprosy with perineural proliferation

A 62-year-old woman, who lived in an area of the United States nonendemic for leprosy, was seen for an enlarging anesthetic lesion that involved the entire left breast. Microscopic examination of skin biopsy specimens taken from the edge of the lesion disclosed chronic perineural inflammation and neural proliferation, with an acid-fast bacillus demonstrable in one nerve. Granulomas, giant cells, epithelioid cells, nerve abscesses, or other characteristics of tuberculoid leprosy were not seen. This woman had a skin lesion of leprosy in an atypical site. It appeared to be indeterminate on pathologic examination and was accompanied by an unusual degree of neural proliferation.     

"Ancient" blue nevi (cellular blue nevi with degenerative stromal changes)

Ancient melanocytic nevi are benign melanocytic neoplasms that show degenerative and atypical changes, sometimes leading to a misdiagnosis of melanoma. We describe 6 patients (M:F ratio 4:2; age range, 15-84 years; median, 50 years) who presented with cellular blue nevi showing stromal changes resembling those of ancient melanocytic nevi. The lesions were located on the buttocks (4 patients) and on the trunk (2 patients) and clinically consisted of heavily pigmented nodules. Histology revealed the architectural pattern of cellular blue nevi. However, the architecture was strikingly altered by stromal changes like those seen in ancient melanocytic nevi, including increased number of large, dilated vessels with pseudoangiomatous features in 4 cases, hyaline angiopathy in 4 cases, myxoid changes, sclerosis or hyalinization of the stroma in all cases, and variable amounts of edema in 4 cases. In 2 cases, a large edematous area was present in the center of the lesion, and nests of ovoidal melanocytes and single dendritic melanocytes appeared to "float" in the stroma. Pleomorphic melanocytes were observed in all cases. Ancient blue nevi represent a morphologic variation of cellular blue nevi-Masson neuronevi with degenerative stromal changes. Recognition of these lesions can help prevent overdiagnosis of melanoma.     

Detection of the interferon-gamma-induced protein 10 in psoriasiform dermatitis of acquired immunodeficiency syndrome

Interferon-gamma-induced protein 10 is a 10-kd protein produced by human keratinocytes following an exposure to interferon gamma. Keratinocytes within psoriatic plaques and within delayed-type hypersensitivity reactions have been shown to stain strongly with an affinity-purified rabbit antibody prepared against interferon-gamma-induced protein 10, suggesting a possible role for interferon gamma in the production of the lesions. A psoriasiform eruption has been seen in patients with acquired immunodeficiency syndrome (AIDS). Its severity appears to correlate with the degree of immunodeficiency in the early stages of AIDS. We stained 10 lesions of psoriasiform dermatitis of AIDS with the anti-interferon-gamma-induced protein 10 antibody using immunoperoxidase techniques. As controls, we studied 10 lesions of non-AIDS psoriasis, six lesions of seborrheic dermatitis with psoriasiform hyperplasia, one lesion of lichen simplex chronicus, and four biopsy specimens of normal skin from patients with AIDS. In addition, normal skin specimens taken from patients with AIDS and human immunodeficiency virus-negative patients at time of autopsy were examined. An identical, strong and diffuse staining pattern was seen in all cases of psoriasiform dermatitis of AIDS, non-AIDS psoriasis, seborrheic dermatitis, and lichen simplex chronicus. The specimens of normal skin showed only weak basal layer staining with anti-interferon-gamma-induced protein 10. Thus, the presence of interferon-gamma-induced protein 10 in keratinocytes was associated with psoriasiform hyperplasia and could be detected in both AIDS-associated and classic psoriasis.     

Clinical and histologic findings in Degos' syndrome (malignant atrophic papulosis)

Records of nine patients (aged ten to sixty-four years) seen at the Mayo Clinic with the typical cutaneous lesions of Degos' syndrome were reviewed. The three patients who died all had central nervous system involvement. The six patients now alive have been evaluated for two to fourteen years and have had their disease for four to fourteen years. Histopathologic examination was performed in all nine cases (total of 27 skin biopsy specimens). Wedge-shaped infarction in the dermis and subcutaneous tissue was observed only in one biopsy specimen from each of three patients, and the infarction occurred in older, well-formed skin lesions. Thrombosis of the arterioles was found in two patients. Hyperkeratosis and dermal acid mucopolysaccharide deposits were common. The most consistent histopathologic finding was lymphocytic infiltrate around and in the walls of venules and arterioles. Various degrees of lymphocyte-mediated necrotizing vasculitis were present in all patients.     

Localized argyria with pseudo-ochronosis.

BACKGROUND: Localized argyria is uncommon and presents clinically as asymptomatic slate gray macules or blue macules resembling blue nevi. Its histopathologic features are usually similar to those of generalized argyria in which silver granules are found most commonly around the eccrine glands, in the walls of blood vessels, and along elastic fibers. Ochre swollen homogenized collagen bundles resembling ochronosis have not been previously described. OBJECTIVE: The purpose of this study is to report a series of 5 patients with localized argyria with the histologic feature of "pseudo-ochronosis." In one patient, biopsy was performed on 2 distinct lesions. METHODS: All patients underwent skin biopsies for light microscopy and darkfield microscopy. In two patients, the biopsy specimens were analyzed with a mass spectrophotometer; scanning electron microscopy and energy-dispersive x-ray analysis were performed. In one patient, the biopsy specimen was decolorized with 1% potassium ferricyanide in 20% sodium thiosulfate. RESULTS: All 5 patients presented with the typical clinical and histologic features of localized argyria. Ochre swollen and homogenized collagen bundles were seen in all cases. In addition, light microscopy in 4 cases revealed an ellipsoid black globule within a zone of collagen degeneration. CONCLUSION: The histologic features of localized argyria include swollen and homogenized collagen bundles resembling ochronosis, "pseudo-ochronosis," which may be more common than previously recognized.     

Dissemination in Cutaneous Leishmaniasis I. Subcutaneous Nodules

In a study of cutaneous leishmaniasis (CL) caused by Leishmania major in Saudi Arabia, 10% of the patients were found to have subcutaneous nodules (SCN). The SCNs were usually inconspicuous, painless, and proximal to the primary skin lesions; when multiple, they showed a "sporotrichoid" configuration or appeared as "beaded cords." Their number ranged from 1-16 (average 3 25 +/- 2.50; mean +/- 1 SD). In some patients, the SCNs seemed to be triggered by antileishmanial treatment. The clinical picture and pathologic findings suggest that SCNs in patients with CL represent lymphatic dissemination, a phenomenon not widely recognized.     

Figurate Purpuric Eruptions on the Trunk: Acetaminophen-induced Rashes

A 23-year-old man had recurrent erythematous purpuric patches in a transverse-linear arrangement on his back and arms. One week prior to a recent episode, he took acetaminophen for 3 days. Four months earlier, he developed the same purpuric lesions at/around the same anatomical site when he took acetaminophen for pain-relief. A biopsy specimen showed capillaritis and extravasation of erythrocytes in the papillary dermis. A provocation test with acetaminophen confirmed these lesions as drug-induced rashes. The uncommon topographic and morphologic features of the purpuric lesion in this patient might be considered as an unusual expression of pigmented purpuric dermatosis caused by acetaminophen.     

Molluscum contagiosum. Ultrastructural evidence for its presence in skin adjacent to clinical lesions in patients infected with human immunodeficiency virus type 1. Military Medical Consortium for Applied Retroviral Research.

BACKGROUND AND DESIGN--Molluscum contagiosum in acquired immunodeficiency disease, although not life threatening, is often a marker of late-stage disease and may lead to disfiguring cutaneous lesions. Although most current therapy results in at least temporary clearing of individual lesions, lesions frequently recur and new lesions arise. Examination of hematoxylin-eosin-stained histologic sections in two patients showed changes suggestive of viral infection in the epidermis 0.5 cm and 1 cm lateral to obvious clinical lesions. These areas were clinically free of any lesions. Both routine histopathologic examination and ultrastructural examination were performed in two patients infected with human immunodeficiency virus type 1 (HIV-1) and three non-HIV-1-infected patients. RESULTS--All patients showed histologic changes diagnostic of molluscum contagiosum. In addition, the sections from HIV-1-infected patients showed areas of acanthosis, hyperkeratosis, and nuclear atypia. Electron microscopy of these areas revealed rare viral organisms in these areas. Similar acanthotic, hyperkeratotic areas were not seen in the biopsy specimens from the non-HIV-1-infected patients and no viral particles were found in the epidermis around the lesions. CONCLUSION--Viral structures consistent with molluscum contagiosum are present within the clinically normal epidermis around lesions of molluscum contagiosum in some HIV-1-infected patients. This may explain the large number of lesions seen in these patients and the difficulty in controlling the spread and recurrence of molluscum contagiosum in HIV-1-infected patients.     

Delay in diagnosis: trauma- and coinfection-related cutaneous leishmaniasis because of Leishmania guyanensis infection

Trauma can trigger the onset of some lesions of cutaneous leishmaniasis (CL). In this study, we present the case of a 65-year-old man who developed persistent, ulcerative, nodular lymphangiitis at the site of elbow abrasions from a fall during a trip to northeastern Brazil. Skin and lymph node biopsy showed tuberculoid granulomatous inflammation and Grocott-methamine silver-positive yeast forms consistent with Sporothrix and Staphylococcus lugdunensis was identified from tissue culture. Antibacterial and antifungal treatment produced short-term healing. Crusted papules recurred at the sites of injury 3 months later and persisted despite therapy. After 15 months, two punch biopsies showed scarring and granulomatous inflammation; cultures and histochemical stains were negative for microorganisms. Because of refractory disease, multiple polymerase chain reaction (PCR) assays for infectious agents on DNA extracted from the biopsy specimens were performed, and Leishmania guyanensis was detected in all specimens. The patient refused pentavalent antimonial therapy and elected for excision of the CL lesions. After 2 years of follow up, he is without disease. CL should be considered in the differential diagnosis in patients who present with ulcerative, nodular lymphangiitis; have a history of travel to endemic regions; and describe a traumatic insult to the affected region. PCR methods for infectious agents increase the sensitivity and specificity of detecting causative agents in these patients who are negative by routine methods. In some, leishmaniasis may be an occult infection whose presence is heralded by trauma. Coinfection, by altering the immune response, may have facilitated the clinical acquisition of CL.     

Persistent and recurrent blue nevi

Persistence of common melanocytic nevi has been fairly well characterized, clinically and histologically. In contrast, persistence of blue nevi has been reported infrequently. To define this entity better, nine cases of biologically persistent and clinically recurrent blue nevi are described. The persistent lesions in four cases were spindle-fascicular blue nevi; one showed senescent or "ancient" change and one had additional deep penetrating/epithelioid blue nevus features with atypical changes worrisome for malignancy. These changes included increased cellularity, cellular pleomorphism, mitotic figures, and a lymphocytic infiltrate. Three were biphasic dendritic-sclerotic/spindle-fascicular blue nevi, one of which had atypical changes. One case was a dendritic-sclerotic ("common") blue nevus. The original histology in one case was unavailable, but the recurrence was a combined blue nevus. The interval from initial biopsy to biopsy of the recurrent lesion was often longer (mean 2.7 years) for recurrent blue nevi than for recurrent common compound or intradermal melanocytic nevi. In addition, in contrast to recurrent common melanocytic nevi, the recurrence, in at least one case, extended beyond the scar of the original excision. These cases demonstrated that blue nevi of all histiotypes and combinations are capable of persistence with clinical recurrence. The persistence usually was histologically similar to the original, but in some cases was more "cellular" because, for the most part, the excisions of the persistent lesion revealed a deeper spindle-fascicular ("cellular") component not evident in the original superficial biopsy. In two cases, the original blue nevus appeared completely banal, but the persistent/recurrent lesions were histologically distinct and demonstrated atypical histologic features. Yet, follow-up (average 3.7 years) supports benign biology. Clinical recurrence is often associated with malignant transformation in blue nevus, but this series demonstrates that malignant tumor progression is not necessarily the case. In the absence of necrosis en mass, marked cytologic atypia, and frequent mitotic figures, the described atypical morphologic parameters in previously biopsied small blue nevi are probably reactive and "pseudomalignant." Awareness of this potential change may avoid diagnostic and prognostic errors.