The Prognostic Value of Histopathological Features in Early-Stage Mycosis Fungoides: Insights from a Retrospective-Prospective Cohort Study.

Primary cutaneous lymphomas (PCLs), especially mycosis fungoides (MF), pose significant diagnostic and therapeutic challenges. This study aims to correlate initial histological features with the disease course and survival in MF patients. A retrospective-prospective cohort study was conducted on 83 patients diagnosed with early-stage MF at the Departments of Dermatovenerology and Pathology, UHC Zagreb, from January 2003 to December 2012. The analyzed histopathological parameters included lichenoid dermal lymphocyte infiltrate, Pautrier microabscesses, and lymphocyte atypia. Patients with more than 30 guardian lymphocytes per 100 keratinocytes exhibited worse overall and progression-free survival. Furthermore, those with over 50% atypical lymphocytes demonstrated a faster progression rate. A dense lichenoid dermal infiltrate and a high count of lymphocyte "keepers" significantly increased the mortality risk within five years of diagnosis. This study did not fully confirm the hypothesis regarding the prognostic value of large Pautrier microabscesses but highlighted the importance of dense lichenoid infiltrates. The study identified new potential histopathological prognostic factors in early-stage MF, suggesting the need for larger studies to confirm these findings. The identification of such predictors could enhance the prognostic stratification and guide more tailored therapeutic approaches for MF patients.

Lichen Sclerosus-Incidence and Comorbidity: A Nationwide Swedish Register Study.

Background: Data on the incidence and comorbidity of Lichen sclerosus (LS), based on validated nationwide population-based registries, remains scarce. Objective: To explore the incidence and association of comorbidities with LS in Sweden, emphasizing its potential links to malignancies and autoimmune disorders. Methods: A population-based retrospective open cohort study was conducted using the National Patient Register to identify all individuals diagnosed with LS (ICD-10 code L90.0) from 1 January 2001 to 1 January 2021. The study included 154,424 LS patients and a sex and age matched control group of 463,273 individuals to assess the incidence and odds ratios for various cancers and premalignant conditions. Results: The incidence of LS in Sweden was 80.9 per 100,000 person per year, with higher incidence in females (114.4) than in males (47.2). LS patients showed an increased odds ratio for vulvar cancer (OR = 8.3; 95% CI = 7.5-9.0), penile cancer (OR = 8.9; 95% CI = 7.3-11.0), prostate cancer (OR = 1.2; 95% CI = 1.1-1.2), testicular cancer (OR = 1.4; 95% CI = 1.1-1.7), bladder cancer (OR = 1.1; 95% CI = 1.1-1.2), breast cancer (OR = 1.4; 95% CI = 1.3-1.4), leukoplakia of the vulva (OR = 253.5; 95% CI = 221.9-289.6), and leukoplakia of the penis (OR = 5.1; 95% CI = 4.9-5.4). Conclusions: This study underscores the significantly increased association of various cancers and premalignant conditions in LS patients, highlighting the critical need for efficacious treatment and diligent follow-up. The association between LS and autoimmune diseases further necessitates comprehensive investigation to understand the underlying mechanisms and clinical management implications. Future research is essential to confirm these findings and elucidate the role of LS in cancer development.

The impact of genital lichen sclerosus in men and women on quality of life: a prospective cohort study.

Background: Genital lichen sclerosus (LS) is a chronic inflammatory skin disorder that affects both sexes of all ages. The clinical characteristics include erosions, redness, and white plaques with atrophic skin, with symptoms such as pruritus, pain, dysuria, and dyspareunia. Objective: This prospective cohort study aimed to assess quality of life (QoL) in men and women with genital LS, both before and after treatment, using the Dermatology Quality of Life Index (DLQI) questionnaire. Methods: Patients diagnosed with genital LS were enrolled continuously in the study and were asked to complete the DLQI questionnaire before treatment and again after individualized treatment 12 weeks apart. Results: This study included 136 patients (48 females and 88 males) diagnosed with genital LS, with a median age of 62 years (range 18-86). The results showed a statistically significant decrease (P < .001) in DLQI score before treatment (median 6.0 [interquartile range (IQR), 1.0-11.0]) compared to after treatment (median 2.0 [IQR, 0.0-4.0)]. In males and females, the median DLQI scores before treatment were 3.0 (IQR, 0.0-10.0) and 8.0 (IQR, 4.5-11.5), respectively, and after treatment were 1.0 (IQR, 0.0-3.0) and 4.0 (IQR, 0.0-9.0), respectively. Females scored significantly higher (P < .001) than males. Limitations: The study's limited generalizability stems from a small sample size of 136 patients, potentially restricting the application of findings to a broader population with genital lichen sclerosus. Additionally, the 12-week follow-up period may not adequately capture the long-term effects of interventions on quality of life. Reliance on self-reported data through the DLQI questionnaire introduces the possibility of bias, as participants may not accurately represent their symptoms and quality of life. The absence of a control group hinders the ability to attribute observed changes solely to the treatment, and the lack of detail on specific interventions makes it challenging to assess the effectiveness of individualized treatment approaches. The wide age range among participants (18-86 years) introduces potential confounding variables, as different age groups may respond differently to treatment. Conclusion: The study findings confirmed that individuals with genital LS experience a small decline in QoL, as observed in both males and females. This study also highlights that effective management of genital LS can significantly improve QoL in both sexes.

Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study.

Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.

The Impact of the COVID-19 Pandemic on Cutaneous Drug Eruptions in a Swedish Health Region without Lockdown.

The incidence of severe cutaneous drug eruptions during the COVID-19 period in Sweden has not been studied previously. Our aim was to compare the incidence of these skin reactions in a Swedish health region during the COVID-19 pandemic period with that of the year after: we conducted a retrospective, observational cohort study using data from a national registry of patients diagnosed with cutaneous drug eruptions during the pandemic in Sweden. We included the number of patients diagnosed with severe cutaneous drug eruptions at the Department of Dermatology in the Jonkoping health region during the COVID-19 pandemic (1 April 2020 to 31 March 2021) and the reference period (1 April 2021 to 31 March 2022). We examined the monthly occurrences of cutaneous drug eruptions in three dermatology clinics within the Jonkoping health region. The frequency of these eruptions was determined for two distinct time periods: during the pandemic and post-pandemic. The study included 102 patients with cutaneous drug eruptions: 29 patients were diagnosed during the COVID-19 pandemic period and 73 were diagnosed during the reference period. The difference in the number of cutaneous drug eruptions cases (p-value = 0.0001, 95% CI 1.4995-3.5500, OR 2.3072) during the pandemic period compared to the post-pandemic period was significant. To our knowledge, the impact of the pandemic on cutaneous drug eruptions has not been investigated in EU countries. The increasing and differentiation of the number of diagnosed cutaneous drug eruptions cases after the pandemic could be explained by the removal of COVID-19 restrictions and the more frequent health-seeking behavior during the post-pandemic period.

Analysis of Teledermoscopy and Face-to-Face Examination of Atypical Pigmented Lesions: a Cross-Sectional, Retrospective Study.

INTRODUCTION: Malignant melanoma (MM) is one of the most fatal skin cancers. Early detection and treatment are crucial for metastasis prevention. The growing number of MM cases has led to an increased need for skin examinations, increasing the healthcare demand in dermatology departments. OBJECTIVES: The purpose of this cross-sectional, retrospective study was to analyze the accuracy and reliability of two different methods, teledermoscopy (TD) and face-to-face examination (FTF), with two different patient groups for MM detection in Jönköping County. METHODS: In teledermoscopic evaluation, a general practitioner takes photographs of a suspected skin lesion (clinical and dermoscopic images) and sends TD referrals to a dermatologist for digital assessment. In the FTF group, the diagnosis was made during regular clinical visits to the dermatology department by a dermatologist. RESULTS: The TD group comprised 55 women and 57 men, and an FTF group comprised 72 women and 66 men. Based on the histopathology report, in the TD group, 75% of suspected MM lesions were accurately classified as MM compared with 57% of suspected MM lesions correctly diagnosed in the FTF group. When compared with histopathology report, the diagnostic concordance of TD and FTF examinations were 80% and 69%, respectively. CONCLUSIONS: We report a high diagnostic concordance between TD and the final histopathological diagnosis. Metrics analyzed for diagnostic accuracy confirmed that TD is an effective and accurate method for early diagnosis of MM. TD is suitable, non-inferior and a useful alternative to FTF examination.

CARDIOVASCULAR RISK IN WOMEN WITH PREECLAMPSIA.

In this study, possible biochemical and functional cardiovascular markers were assessed in women with preeclampsia. Fifty-five pregnant women with manifest moderate (mild) preeclampsia (PE) and fifty healthy women as a control group were included in this prospective study. Laboratory tests including lipid panel, C-reactive protein (CRP), and homocysteine levels as biohumoral markers of atherogenesis, as well as ergometry and the main cardiovascular risk factor markers were performed in all women during pregnancy and six months after delivery. In our study, cholesterol and LDL levels in the PE group did not differ from those in the control group. Triglyceride levels in the PE group were higher than the corresponding values found in normal pregnancies, while HDL levels were significantly lower in the PE group than in the normal pregnancy group (p<0.001). The values of total cholesterol, LDL, HDL, and triglycerides in the PE group were higher compared to those in the same group six months after delivery (p<0.001). The effect of PE as an inflammatory disease could be confirmed to a certain extent by elevated CRP levels (p<0.001). A very high percentage of negative exercise stress tests indicated a good cardiovascular response to the current PE in the otherwise healthy pregestational women. It could be concluded that the development of possible cardiovascular comorbidities in preeclamptic pregnant women is a long process, but also due to etiologic factors of coexistent metabolic disorders such as dyslipidemia, as well as elevated inflammatory markers and homocysteine, PE can be considered even an early predictor of cardiovascular disease.

Morbihan Disease - An Old and Rare Entity Still Difficult to Treat.

Morbihan disease (MD), also known as Morbihan syndrome, "solid persistent facial edema and erythema", "rosacea lymphedema", and "solid facial edema in acne", is a rare and often unrecognizable entity, that presents with a slow occurrence of persistent lymphoedema of the upper two-thirds of the face (1,2). A 30-year-old woman presented to our Department with persistent, asymptomatic face edema and erythema lasting for 18 months. She was previously treated for rosacea with doxycycline (100 mg/day for four months) without improvement. Dermatological examination revealed erythematous, nonpitting, solid edema located on the mid-forehead, nose, and cheeks with sparse erythematous papules and pustules on the entire face including the chin and comedones, papules, and pustules on the back (Figure 1 and Figure 2). She was otherwise healthy and was not taking any medication. Laboratory tests with immunological tests and Quantiferon test together with MRI of the orbits, chest X-ray, chest high-resolution computed tomography, cranial X-ray, and abdominal ultrasound were all within normal limits. Histopathology revealed dermal edema, perivascular and peri-adnexal lymphohistiocytic infiltrate, and sebaceous gland hyperplasia. Based on the typical clinical picture, histopathological findings, and the exclusion of several differentials the diagnosis of MD was established. The patient was treated with oral isotretinoin (20 mg/day for eight months) without regression of solid edema and erythema on the face but with complete regression of acne on the trunk. She was started on oral corticosteroids (prednisolone, 20 mg/day for two months followed by reduction of the dose over three months), again with only slight short transient improvement and rapid relapse of facial erythema and edema. The patient refused any other suggested treatment. We treated our patient for a total 2 years and followed up for 5 years. The pathogenesis of MD is still unknown. It is considered a clinical variety or a complication of rosacea or acne which does not tend to regress spontaneously. It is believed that chronic inflammation in patients with MD is due to acne or rosacea causing structural damage to blood and lymph vessels (1,3,4). However, cases of MD without previous history of rosacea and acne have been reported supporting the distinct disease theory (3,4). Edema and erythema are localized on the upper half of the face affecting the forehead, glabella, eyelids, nose, and cheeks. Although the symptoms may come and go, MD usually does not improve without treatment (5). Several therapeutic options have been reported, although there is no established standard treatment for MD. Reported therapy includes short-term oral isotretinoin (0.5 mg/kg/day), long-term oral isotretinoin (40-80 mg/day, 10-24 months), long-term doxycycline, combination of systemic corticosteroids and antibiotic (prednisolone 20 mg/day for 2 weeks and doxycycline 200 mg/day for 12 weeks), slow-releasing doxycycline monohydrate (40 mg/day for 6 months), long-term minocycline (50 mg/day for 4 months), and a combination of both oral retinoid and ketotifen (isotretinoin 0.7 mg/kg/day for 4 months, ketotifen 2 mg/day for 4 months) (1,2,6,8). The disease is frequently recalcitrant to therapy, and only several cases of successfully treated patients with MD have been reported (1,2,4, 6-8). We presented a patient with characteristic features of MD, which is a persistent, cosmetically disturbing condition, unfortunately mostly refractory to therapeutic measures.

Hyperpigmented Mycosis Fungoides - A Rare Entity.

Dear Editor, A 67-year-old man of Kosovar-Albanian ethnic origin (skin phenotype IV) presented to our dermatology clinic with generalized hyperpigmented patches and plaques all over the body, so-called melanoerythroderma (Figure 1). The lesions, which first appeared nearly six years ago, developed gradually; they were diagnosed as mycosis fungoides (MF), and were subsequently treated only with topical corticosteroids. We performed further examinations upon admission to our department. Relevant laboratory parameters - blood cell count, LDH, urinalysis, and serum chemistry - were within normal limits. Endocrinological examination excluded Addison disease, and the patient was not receiving any drugs that could cause skin hyperpigmentation. Chest-abdomen-pelvis computed tomography (CT) scan and sternal puncture were normal. Flow cytometric immunophenotyping revealed less than 5% aberrant T-cells. Histopathology and immunohistochemistry of skin specimens revealed lichenoid infiltration of small- to medium-sized atypical T-lymphocytes within the upper dermis, epidermotropic lymphocytes with several Pautrier's microabscesses (Darier's nests), pigment incontinence, abundant melanophages in the papillary dermis (Figure 2, a, b), and the T-cell CD4+CD7-CD8+ phenotype (Figure 2, c, d). Based on the clinical picture, histopathology, and immunohistochemistry the diagnosis of hyperpigmented mycosis fungoides (MF) stage IIIA (T4N0M0B0) was established. Skin-oriented therapy (retinoids-PUVA) resulted in slight improvement. Hyperpigmented MF is a rare, uncommon, clinical variant of MF, with a predilection for dark-skinned people (1). Only a few cases of hyperpigmented MF have been reported so far, and our case being one of them (2-5). Hyperpigmented patches or/and plaques dominate the clinical picture. Hyperpigmented MF is characterized by a predominantly CD8+ epidermotropic T-cell phenotype, although different phenotypes have been reported (CD4+ or CD4-CD8-) (2). Histopathologically, interface changes, pigment incontinence and melanophages are usually found in addition to the classical findings of early MF (1). The exact mechanism of hyperpigmentation is not well understood. Hyperpigmented MF had an indolent course in most reported cases, and skin-directed therapy is therefore the treatment of choice. Although MF and its hyperpigmented variant is a lymphoma of low-grade malignancy, large-cell transformation (CD30+) of hyperpigmented MF can occur (1). These rare cases of special clinical MF variants are extremely valuable and can help us investigate and understand the pathophysiology of the disease. Treatment and close follow-up is mandatory in the hyperpigmented variant of MF.

Poikilodermatous Mycosis Fungoides - Rare Entity, Different Treatment Modalities.

Poikilodermatous mycosis fungoides (PMF) is a rare clinical variant of early-stage MF with peculiar histological features. Poikiloderma occurs in many different clinical conditions, which makes a diagnostic procedure more complicated. PMF belongs to a group of MF variants with low risk of disease progression. We report a case of a 64-year-old woman, who presented with mottled skin aspect of erythema, poikilodermatous patches (hypopigmentation, hyperpigmentation, atrophy, and telangiectasia) on more than 80% of the body. Based on clinical, histopathological, and immunohistochemical findings, we established the diagnosis of PMF. Staging procedure determined stage IIA. As skin-directed therapy was the treatment of choice, the patient was successfully treated with psoralen-UVA (PUVA), nbUVB plus retinoid (Re-nbUVB), and PUVA plus retinoid (Re-PUVA), however, with rapid recurrence.

Blistering diseases in the mature patient.

Autoimmune blistering diseases (AIBD) are a group of chronic diseases affecting the skin and mucous membranes, with different presentation, clinical course, histologic and immunopathologic findings, and different therapeutic approach. Blisters develop as a result of autoantibodies directed against distinct adhesion structures within desmosomes or within the basement membrane zone. The most common AIBD that develops in the elderly is bullous pemphigoid (previously also named "pemphigoid senilis"), but mature patients can also present with other AIBD as mucous membrane pemphigoid, epidermolysis bullosa acquisita, paraneoplastic pemphigus, pemphigus vulgaris, pemphigus foliaceus, linear IgA dermatosis, and dermatitis herpetiformis. There are no differences in treatment approach to mature patients with AIBD, but due to more common comorbidities, systemic therapy should be given with more caution and control, and due to distorted skin integrity in the aged skin, the safety concerns are increased with the long-term use of any topical medication.

Folliculotropic Mycosis Fungoides Associated with Autoimmune Hepatitis.

Dear Editor, the association between lymphomas and autoimmune manifestations, as well as the prevalence of the cases of coexistent lymphomas and autoimmune conditions, has not been completely established (1-3). Since cutaneous T-cell lymphoma (CTCL) cases are rare, any hypothesis can only be based on case reports or small case series. We present the case of a male patient with folliculotropic mycosis fungoides (FMF) and synchronous autoimmune hepatitis (AIH) with extremely high levels of cancer antigen 19-9 (CA 19-9). The patient was under the supervision of a multidisciplinary team consisting of dermatologists, hepatologists, and hematologists. The patient died 15 months after the diagnoses of FMF and AIH were established and 3.5 years after the first skin changes. Based on our knowledge and search of medical databases, this is the first case of AIH in a patient with CTCL, i.e. with MF. A 53-year-old male patient was admitted to our Dermatology Clinic in September 2014 after being briefly treated with acitretin. During hospitalization, he was diagnosed with FMF, autoimmune hepatitis, and newly developed diabetes mellitus. At the time of hospital admission, about 70 percent of the surface of the skin was affected, infiltrated with numerous cysts on the face, neck, and upper thorax. The patient also presented with alopecia affecting most of the scalp, loss of eyebrows and eyelashes (Figure 1), and complained of intensive itching. The clinical presentation suggested the diagnosis of FMF, which was later confirmed based on histological (Figure 2) and immunohistochemical (Figure 3) findings. The histochemical staining method PAS-Alcian did not reveal mucin deposits. Immunohistochemical findings revealed tumor cells to show aberrant T-immunophenotypes - CD3+, CD2+, CD5-, CD7-, CD4+, CD8-, CD30-. Due to elevated serum conjugated bilirubin and extremely high levels of hepatocellular and cholestatic liver enzymes, the patient was transferred to the Gastroenterology Department. Diagnosis of AIH was established based on the liver biopsy (highly active autoimmune hepatitis) and the exclusion of viral etiology, drug-induced hepatotoxicity, and inherited metabolic disorders of the liver. CA 19-9 level was extremely high (4475.0; RR <37.0 µg/L). In March 2015, CA 19-9 decreased to 365.3. In April 2015, erythroderma and small isolated tumors on the trunk and extremities developed. The patient was treated with RE-PUVA and radio-therapy. In June 2015, due to systemic symptoms, the patient was started on PUVA with IFNα. In November 2015, erythroderma persisted together with larger and ulcerated tumors. The patient was treated at the Hematological Department with two cycles of cyclophosphamide, vincristine, doxorubicin, and methylprednisolone. From March 2015, the patient was continuously treated with ursodeoxycholic acid, prednisolone, azathioprine, analog insulin, and allopurinol. MSCT revealed lymphoma infiltrates in the liver, spleen, and peritoneum (gross tumors). The immunophenotypic analysis of the cells in ascites revealed atypical lymphocytes with convoluted nuclei - LCA+, CD3+, CD20-. The patient died in December 2015 due to sepsis with febrile neutropenia. Before death, he suffered from candidiasis and toxic liver damage due to fluconazole. FMF is an aggressive MF variant with infiltration of lymph nodes, visceral involvement at an earlier stage, and decreased life expectancy (4). Autoimmune hepatitis (AIH) is still an unclear progressive liver disease of unknown etiology which features hypergammaglobulinemia, detectable autoantibodies, and interface hepatitis (5). Being exposed to xenobiotic (acitretin) with consequent liver damage could lead to the formation of self-antigens to which the patient's immune system might have sensitized, and the autoimmune attack continued (6). Slightly elevated CA 19-9 levels in autoimmune hepatitis were reported by other authors (7-9). It should be noted that the liver involvement with atypical lymphocytes can be diffuse without any detectable nodules on a CT scan (4). Soluble liver antigen and liver-pancreas antibodies, together with CA 19-9, need to be implemented as routine diagnostic tools to rationalize the usage of tumor markers in day-to-day practice as well in diagnosis of AIH (10).

Nodular Prurigo Associated with Mycosis Fungoides - Case Report.

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and accounts for approximately 50% of all lymphomas arising primarily in the skin. The three types of MF lesions are patches, plaques, and tumors, according to which the disease is traditionally divided into three clinical stages. The clinical course can be protracted and take years or decades. In the final stage, MF evolves to a systemic form of the disease. Nodular prurigo (NP) is still a condition of unknown etiology characterized by papulonodular eruption and intense pruritus. Multiple diseases, including dermatological, systemic, and psychiatric diseases, have been assumed to cause NP. Pruritic skin lesions have been known to precede clinically evident B and T cell lymphomas for years. In the literature, pruritus and NP have been reported in patients affected by systemic Hodgkin and non-Hodgkin lymphomas. Only two cases of cutaneous lymphoma as underlying disease in patients with PN have been reported in the literature. We report a rare case of a patient with concomitant non-Hodgkin skin lymphoma - MF and NP. Our female patient with a 10-year history of MF stage IIb during the last three years had been presenting for regular check-up with itchy, newly formed, rarely disseminated nodules 5-8 mm in diameter on the forearms and lower legs. Sharply limited erythematosquamous, slightly infiltrated foci (as part of MF as the underlying disease) were visible on the trunk and extremities. Extracutaneous involvement of MF was excluded. We performed a biopsy on a nodule from the lower leg to rule out tumor stage MF; the biopsy confirmed NP. We conclude that prurigo nodules should not be confused with tumor stage MF. NP is a therapeutic challenge for any dermatologist. Any underlying diseases should be treated first.