Parinaud's oculoglandular syndrome: Coinfection by Bartonella henselae and Sporothrix brasiliensis.

A 26-year-old woman presented an eyelid lesion, after being scratched by a cat that had a similar skin lesion. It evolved into a cervical lymph node enlargement. With a hypothesis of Parinaud´s oculoglandular syndrome (POS) due to cat scratch disease (CSD), doxycycline was prescribed. After two weeks of treatment without improvement, a biopsy and blood sample were obtained. Itraconazole was prescribed and the skin lesion improved, but not the lymph node enlargement. A Sporothrix schenckii complex was isolated from the skin sample. Also, a specie-specific polymerase chain reaction detected Bartonella henselae DNA in her blood sample. Azithromycin was included to treat the bacterial infection, whereupon the lymph node also receded successfully. Sporotrichosis and CSD are zoonoses that can be transmitted to humans by traumatic inoculation due to scratches or bites from cats. Both can evolve with POS. Patients who present skin lesions and/or POS after being wounded by a cat should be investigated for both diseases.

Misleading subcutaneous mycosis: a case report of subsequent clinical mycetoma-like and histological chromoblastomycosis-like lesions.

Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an immunocompromised patient who presented rare manifestations of opportunistic mycoses: mycetoma-like hyalohyphomycosis on his right foot caused by Colletotrichum gloeosporioides, followed by cutaneous phaeohyphomycosis on his right forearm caused by Exophiala oligosperma. Further to the rarity of this case, the patient's lesion on the foot shows that the clinical aspects of mycetomas could falsely appear in other fungal infections similar to hyalohyphomycosis. We also show that the muriform cells that were seen in the direct and anatomopathological examination of the skin are not pathognomonic of chromoblastomycosis, as observed in the lesion of the patient's forearm.

The Expression of PRAME as an Aid for Diagnosis and Evaluation of Histologic Margins of Intraepidermal Cutaneous Melanoma in Xeroderma Pigmentosum Patients.

Xeroderma Pigmentosum (XP) is a genetic disorder characterized by photosensitivity, dyschromia, and high risk of skin cancer. From a clinical and histologic view, it can be difficult to diagnose cutaneous melanoma (CM) in XP patients and to define its resection margins. We aimed to study the role of PRAME (PReferentially Expressed Antigen in MElanoma) in differentiating intraepidermal CM from superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and evaluating the histological margins of CMs. We included XP patients. melanocitic and nonmelanocytic lesions with adjacent skin, and, as control groups, sun-damaged skin from non-XP individuals. Melanocytic lesions with a consensus diagnosis were grouped into CM, SAMPUS, or benign. The selected samples were PRAME-immunoshistochemically stained, and the ratio between immuno-positive cells/mm was recorded, according to Olds and colleagues for intraepidermal lesions. Lezcano and colleagues' method was used for intradermal lesions. Clinical data from XP patients were reviewed. All 9 patients were alive and well at the study closure, even those who developed melanoma metastases. Positive/diffuse PRAME expression was found in 29% (7/24) of intraepidermal CMs and 20% (1/5) SAMPUS samples. All 103 XP control samples and 24 adjacent lesions skin of non-XP patients were PRAME negative. This was a single-center and retrospective study, using a relatively small sample, limiting our conclusions. In XP patients' lesions, PRAME expression could help in the setting of challenging melanocytic tumors and surgical margins evaluation. It is also possible that the method can avoid overdiagnosis and, consequently, more aggressive treatment recommendation in unequivocal CM cases.

Role of tangential biopsy in the diagnosis of nail psoriasis.

BACKGROUND: Histopathology can be crucial for diagnosis of inflammatory nail diseases. Longitudinal excision and punch biopsies are the most used techniques to obtain the tissue sample. However, there is a low clinical-histopathological correlation, besides the risk of nail dystrophy. Tangential excision biopsy (TB) is a well-established technique for the investigation of longitudinal melanonychia. TB could also be used to evaluate diseases in which histopathological changes are superficial, as in psoriasis. OBJECTIVE: To study the value of TB in the histopathological diagnosis of nail psoriasis. METHODS: This is a prospective and descriptive study of the clinical-histopathological findings of samples from the nail bed or matrix and nail plate of 13 patients with clinical suspicion of nail psoriasis. Biopsies were obtained through partial nail avulsion and TB. RESULTS: In nine patients, the hypothesis of psoriasis was confirmed by histopathology; in one, the criteria for diagnosing nail lichen planus were fulfilled. The tissue sample of only one patient did not reach the dermal papillae, and, in four of 13 patients, the adventitial dermis was not sampled. No patient developed onychodystrophy after the procedure. STUDY LIMITATIONS: In three patients, the clinical and, consequently, histopathological nail changes were subtle. Also, in one patient's TB didn't sample the dermal papillae. CONCLUSIONS: TB is a good option to assist in the histopathological diagnosis of nail psoriasis, especially when appropriate clinical elements are combined. Using this technique, larger and thinner samples, short postoperative recovery time, and low risk of onychodystrophy are obtained.

Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy- A comparative study.

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Is Bartonella sp. infection relevant in hematological malignancies in HIV-negative patients? A literature review.

Bartonelloses are diseases caused by Bartonella sp., transmitted to humans by blood sucking arthropod vectors. Clinical presentations include bacillary angiomatosis, cat scratch disease and atypical forms. We performed a review of cases of bartonelloses and hematological malignancies published in HIV-negative patients. Terms used were Bartonella or Bacillary Angiomatosis and Leukemia, Lymphoma, Multiple Myeloma, or Cancer. Fifteen cases met our criteria. Clinical presentations included bacillary angiomatosis, chronic fever, chronic lymphadenopathy, osteomyelitis, neuroretinitis, chronic anemia and hepatosplenic peliosis. Fourteen patients were asymptomatic after antibiotic therapy, and one died before antibiotic treatment. Clinicians should be suspicious of Bartonella sp. infections in immunocompromised patients.

IL-1ß and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

BACKGROUND: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). OBJECTIVE: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. METHODS: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. RESULTS: Skin samples from CLE/SLE+patients presented higher expression of IL-1ß (ARC-82: p=0.024; SLICC-12: p=0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p=0.0097; SLICC-12: p=0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p=0.0003; SLICC-12: p=0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p=0.0257; SLICC-12: p=0.0285) and CD8+ cells (ARC-82: p=0.0075; SLICC-12: p=0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p=0.0024; SLICC-12: p=0.0116). STUDY LIMITATIONS: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. CONCLUSIONS: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1ß, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Misleading subcutaneous mycosis: a case report of subsequent clinical mycetoma-like and histological chromoblastomycosis-like lesions

ABSTRACT Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an immunocompromised patient who presented rare manifestations of opportunistic mycoses: mycetoma-like hyalohyphomycosis on his right foot caused by Colletotrichum gloeosporioides, followed by cutaneous phaeohyphomycosis on his right forearm caused by Exophiala oligosperma. Further to the rarity of this case, the patient's lesion on the foot shows that the clinical aspects of mycetomas could falsely appear in other fungal infections similar to hyalohyphomycosis. We also show that the muriform cells that were seen in the direct and anatomopathological examination of the skin are not pathognomonic of chromoblastomycosis, as observed in the lesion of the patient's forearm.

Detection of Bartonella henselae DNA in the blood of patients with livedoid vasculopathy

Abstract Background: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. Objective: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. Methods: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. Results: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). Study limitations: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. infection. Conclusion: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Detection of Bartonella henselae DNA in the blood of patients with livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. OBJECTIVE: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. METHODS: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. RESULTS: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). STUDY LIMITATIONS: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. CONCLUSION: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Scarring versus Non-Scarring Alopecia: An Interobserver Histopathological Reproducibility Study.

Introduction: Distinguishing scarring (SA) versus non-scarring alopecia (NSA) may not be a simple procedure on either clinical or histopathological views. Aims: We sought to study the interobserver variability in the histopathological assessment of SA versus NSA, including clinical-pathological considerations. Methods: Two dermatopathologists independently interpreted the same set of 100 specimens (89 patients). The samples were serial sectioned and stained by hematoxylin and eosin and Verhöeff methods. The patients' mean age was 46 years, with 13 being males and 76 females. Results: In 16/100 samples, there was no consensus among the two examiners regarding SA versus NSA (weighted kappa = 0.6583; 95% CI); 3/16 patients were re-biopsied, and in the second sample, consensus was reached. In 76/89 patients, the anatomopathological examination was helpful in defining the SA versus NSA subtype. Of the 84 samples in which there was interobserver agreement, 4 which had been considered scarring in the routine pathological report were re-classified as non-scarring, whereas one biopsy, previously diagnosed as non-scarring, was now considered cicatricial due to the newly found areas of lichenoid inflammation in the infundibular epithelium. Discussion: The ideal scalp examination may require deep serial biopsy sectioning, elastic tissue stain, re-biopsy, and strict clinical-evolutive correlation.

Congenital solitary reticulohistiocytosis (Hashimoto - Pritzker)

Abstract Congenital and self-healing Hashimoto-Pritzker reticulohistiocytosis is the benign variant of the Langerhans cell histiocytosis (LCH) group. It is characterized by multiple skin lesions (congenital or appearing during the first days after birth), without systemic manifestations and spontaneous resolution in days to months. The authors report the case of a boy with a single congenital leg skin lesion, a rare disease variant. Through histopathology, a dense skin infiltration of S100 protein-, CD1a-, CD207-immunomarked cells was found. KI67 index was high (62%). A complete spontaneous resolution occurred 07 days after the biopsy (25 days after birth). Monolesional disease, distal limb lesion, absence of lesions in the mucous membrane or seborrheic area, and less than 25 percent of LCs with Birbeck granules were said to be possible clues for a favorable prognosis in LCs histiocytosis. But, as a precautionary measure, the child will be followed up until at least 2 years of age.