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.

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-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.

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.

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.

Dermatological manifestations relating to nutritional deficiencies after bariatric surgery: case report and integrative literature review

ABSTRACT BACKGROUND: The number of bariatric surgeries performed worldwide is growing. Among the main short, medium or long-term complications after surgery are nutritional deficiencies. Many of these, such as those of Zn, Cu and vitamins A, B1, B3, B6 and B12, are manifested by dermatological lesions before potentially fatal systemic disorders occur. OBJECTIVE: To identify the main dermatological manifestations associated with nutritional deficiencies after bariatric surgery, and the associated variables. DESIGN AND SETTING: Integrative literature review carried out at a public university in Brazil. METHODS: This was a case report and a review of health research portals and databases of national and international biomedical journals, without publication date limitation. The descriptors used for searches followed the ideal methodology for each database/search portal: "bariatric surgery", "skin", "skin disease", "skin manifestation", "deficiency disease" and "malnutrition". RESULTS: A total of 59 articles were selected, among which 23 were review articles or articles that addressed specific dermatological manifestations. The other 36 articles described 41 cases, which were organized into a table with the clinical variables. CONCLUSIONS: Although nutritional deficiencies are expected as complications after bariatric surgery, few articles relating them to their dermatological manifestations were found. It is important to recognize skin changes caused by nutritional deficiencies in patients treated via bariatric surgery, as these may occur before systemic complications appear and are easier to diagnose when the patient does not have any systemic symptoms yet. However, there is generally a delay between the appearance of skin lesions and making the diagnosis of nutritional deficiency.

Congenital solitary reticulohistiocytosis (Hashimoto - Pritzker).

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.

Dermatological manifestations relating to nutritional deficiencies after bariatric surgery: case report and integrative literature review.

BACKGROUND: The number of bariatric surgeries performed worldwide is growing. Among the main short, medium or long-term complications after surgery are nutritional deficiencies. Many of these, such as those of Zn, Cu and vitamins A, B1, B3, B6 and B12, are manifested by dermatological lesions before potentially fatal systemic disorders occur. OBJECTIVE: To identify the main dermatological manifestations associated with nutritional deficiencies after bariatric surgery, and the associated variables. DESIGN AND SETTING: Integrative literature review carried out at a public university in Brazil. METHODS: This was a case report and a review of health research portals and databases of national and international biomedical journals, without publication date limitation. The descriptors used for searches followed the ideal methodology for each database/search portal: "bariatric surgery", "skin", "skin disease", "skin manifestation", "deficiency disease" and "malnutrition". RESULTS: A total of 59 articles were selected, among which 23 were review articles or articles that addressed specific dermatological manifestations. The other 36 articles described 41 cases, which were organized into a table with the clinical variables. CONCLUSIONS: Although nutritional deficiencies are expected as complications after bariatric surgery, few articles relating them to their dermatological manifestations were found. It is important to recognize skin changes caused by nutritional deficiencies in patients treated via bariatric surgery, as these may occur before systemic complications appear and are easier to diagnose when the patient does not have any systemic symptoms yet. However, there is generally a delay between the appearance of skin lesions and making the diagnosis of nutritional deficiency.

Immunophenotypic profile of macrophages in generalized pustular psoriasis and deficiency of the interleukin-36 receptor antagonist.

M2 macrophages are copious in generalized pustular psoriasis (GPP). M2 macrophages seem to acquire new skills and share common characteristics in GPP. HAM56 may play a role in attracting immature neutrophils to the inflammatory environment in GPP.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient.

As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.