Generalized Verrucosis Revealing a Life-Threatening and Unlabeled T-Cell Lymphopenia Associated With Autoimmune Hemolytic Anemia: A Case Report and Review of Literature.

Primary immunodeficiencies are inherited disorders, which may be revealed in the context of autoimmune hemolytic anemia (AIHA). We report the case of a girl presenting with an enterovirus-related AIHA. Despite being in complete remission for her anemia after treatment, the initial CD4/CD8 lymphopenia dramatically worsened with time. Its sole clinical presentation was generalized verrucosis. Cellular quantitative and functional immunodeficiency was evidenced but no known molecular defect was identified despite extensive workup. This unlabeled profound naive T-lymphopenia was cured by bone marrow transplantation. No similar case was ever described in the scientific literature. Patients with AIHA and/or generalized verrucosis should be screened for primary immunodeficiency, before initiating any immunomodulatory treatment.

Elephantiasis nostras verrucosa: an atypical presentation following intrapelvic lymphoma.

Elephantiasis nostras verrucosa is a progressively debilitating and disfiguring disease commonly presenting with verrucous, cobblestone-like papules, nodules, or plaques with nonpitting edema in the lower extremities. Histopathology is marked by hyperkeratosis and dermal or subcutaneous fibrosis as a result of chronic lymphedema. Risk factors include obesity, recurrent cellulitis, chronic venous insufficiency, congestive heart failure, scleroderma, radiation, trauma, and tumors. We report a 72-year-old man who presented to the dermatology clinic for an 11-year history of edematous legs, occasionally associated with ulcerations. The findings developed within a year of intrapelvic non-Hodgkin lymphoma and progressed gradually over 10 years after lymphoma remission. Physical examination revealed atypical features including compressible cysts and pitting edema extending from the lower legs to the thighs bilaterally. The patient was noncompliant for the recommended compressive devices and the condition progressively worsened over the course of 7 months of follow-up. Early interdisciplinary management using compressive devices and a lymphatic pump are recommended. Underlying causative factors should be assessed with regular follow-up to optimize treatment outcomes.

The Successful Treatment of Elephantiasis Nostras Verrucosa With Ablative Carbon Dioxide Laser.

BACKGROUND AND OBJECTIVE: Elephantiasis nostras verrucosa (ENV) is a disfiguring skin condition that is difficult to treat. Existing treatment modalities serve to improve cosmesis or treat symptoms. Herein, we report a case of ENV with lymphocutaneous fistula successfully treated with ablative carbon dioxide laser. STUDY DESIGN/PATIENTS AND METHODS: A 57-year-old woman with biopsy-proven ENV with lymphocutaneous fistula was treated with ablative carbon dioxide laser to the symptomatic area of her right thigh in 3 treatment sessions over 6 months. RESULTS: The patient had resolution of lymphocutaneous drainage as well as 90% improvement in the appearance of ENV lesions at the 1-month follow-up visit. CONCLUSION: Ablative carbon dioxide laser may provide cosmetic, symptomatic, and medical benefit for patients with localized ENV.

Beta Human Papillomavirus Infection Is Prevalent in Elephantiasis and Exhibits a Productive Phenotype: A Case-Control Study.

Elephantiasis is considered a cutaneous region of immune deficiency with cobblestone-like surface caused by a wart-like eruption. Verrucosis is a diffuse human papillomavirus (HPV) infection linked to immunodeficiency disorders. The objective of this study was to examine the prevalence of HPV infection in lymphedema and its pathogenic role in elephantiasis. A retrospective case-control study was performed examining lymphedematous skin and controls of peritumoral normal skin. HPV infection was evaluated at the DNA, protein, and histopathologic levels by polymerase chain reaction, immunohistochemistry, and light microscopy, respectively. Overall, 540 HPV DNAs were detected in 120 of 122 cutaneous samples (median 4 HPV DNAs per sample, range 0-9). Compared with controls, no differences existed in type or number of HPVs identified. Instead, a diverse spectrum of HPV-related histopathologies were evident, likely reflecting the multiplicity of HPV genotypes detected. Most notably, increasing histopathologic lymphedema stage significantly correlated with markers of productive HPV infection such as altered keratohyaline granules and HPV L1 capsid expression. Limitations of this study are the absence of normal skin controls not associated with neoplasia or subclinical lymphedema, and lack of assessment of HPV copy number per keratinocyte infected. In conclusion, productive HPV infection, not HPV type or numbers detected, distinguished lymphedematous skin from controls. These findings support the theory that lymphedema creates a region of depressed immunity that permits productive HPV infection, manifested clinically by diffuse papillomatosis, characteristic of elephantiasis.

Detecting and staging podoconiosis cases in North West Cameroon: positive predictive value of clinical screening of patients by community health workers and researchers.

BACKGROUND: The suitability of using clinical assessment to identify patients with podoconiosis in endemic communities has previously been demonstrated. In this study, we explored the feasibility and accuracy of using Community Health Implementers (CHIs) for the large scale clinical screening of the population for podoconiosis in North-west Cameroon. METHODS: Before a regional podoconiosis mapping, 193 CHIs and 50 health personnel selected from 6 health districts were trained in the clinical diagnosis of the disease. After training, CHIs undertook community screening for podoconiosis patients under health personnel supervision. Identified cases were later re-examined by a research team with experience in the clinical identification of podoconiosis. RESULTS: Cases were identified by CHIs with an overall positive predictive value (PPV) of 48.5% [34.1-70%]. They were more accurate in detecting advanced stages of the disease compared to early stages; OR 2.07, 95% CI = 1.15-3.73, p = 0.015 for all advanced stages). Accuracy of detecting cases showed statistically significant differences among health districts (χ2 = 25.30, p = 0.0001). CONCLUSION: Podoconiosis being a stigmatized disease, the use of CHIs who are familiar to the community appears appropriate for identifying cases through clinical diagnosis. However, to improve their effectiveness and accuracy, more training, supervision and support are required. More emphasis must be given in identifying early clinical stages and in health districts with relatively lower PPVs.

Abdominal Elephantiasis Nostras Verrucosa: An Underrecognized Disorder.

Case 1 A 60-year-old African American man presented with a medical history of morbid obesity (weighing more than 550 lb), benign prostatic hyperplasia, hyperlipidemia, gynecomastia, atrial fibrillation, hypertension, chronic obstructive pulmonary disease, psoriasis, sleep apnea, and cardiomegaly. His size has limited his ability to clean himself properly. He experiences chronic and recurrent skin irritation and cellulitis possibly secondary to intertriginous superinfection, lymphedema, and venous stasis. On examination, his abdomen showed heavy skinfolding with hyperpigmentation, cobblestone and velvety changes, thickening and fibrotic induration of the skin, focal areas of redness, and tenderness on palpation (Figure 1A and 1B). These findings are consistent with a clinical picture of chronic elephantiasis nostras verrucosa (ENV) and lipodermatosclerosis (LDS). He has had numerous hospitalizations for recurrent cellulitis in the abdomen and lower limbs during the past 8 years. He is currently residing in a weight-loss facility and is managing skin care using topical nystatin powder and periodic topical triamcinolone ointment.

Histopathological and immunohistochemical features of nodular podoconiosis.

BACKGROUND: Podoconiosis is a familial geochemical dermatosis which is common in Ethiopia but relatively unknown in Europe/United States. It is related to exposure of bare feet to volcanic soil and presents with extensive bilateral lymphedema of legs and feet. Histopathological and immunohistochemical features of it have not been described yet. OBJECTIVES: The objectives of this study are to characterize podoconiosis histopathologically and immunohistochemically and to increase awareness of the disease. METHODS: Ten specimens of fully developed podoconiosis were examined with hematoxylin/eosin, periodic acid-Schiff, Gram, elastica-van Gieson stainings, with immunohistochemistry (CD3,CD20,CD31,CD68,CD138, tryptase, podoplanin, collagen IV), and with polymerase chain reaction (PCR) for human papillomavirus (HPV)-specific DNA. RESULTS: All specimens showed verrucous acanthosis and papillomatosis. Eccrine ducts demonstrated hyperplasia, syringofibroadenomatous changes and miliaria. Dermal collagen bundles were thickened, and elastic fibers were dramatically reduced. A moderate lymphoplasmacytic infiltrate was joined by mast cells and scattered macrophages; neutrophils and eosinophils were sparse. Blood vessels were increased, dilated, and often sclerotic while lymphatics were reduced and largely not dilated. HPV-PCR was negative in all specimens. CONCLUSIONS: Podoconiosis demonstrates distinctive changes of chronic lymphedema with extensive sclerosis, loss of elastic fibers, verrucous acanthosis (not HPV induced) and reactive changes of eccrine structures. Mast cells, macrophages and altered blood vessels may be involved in the pathogenesis.

Epidemiology of elephantiasis with special emphasis on podoconiosis in Ethiopia: A literature review.

Elephantiasis is a symptom of a variety of diseases that is characterized by the thickening of the skin and underlying tissues, especially in the legs, male genitals and female breasts. Some conditions having this symptom include: Elephantiasis nostras, due to longstanding chronic lymphangitis; Elephantiasis tropica or lymphatic filariasis, caused by a number of parasitic worms, particularly Wuchereria bancrofti; non-filarial elephantiasis or podoconiosis, an immune disease caused by heavy metals affecting the lymph vessels; proteus syndrome, the genetic disorder of the so-called Elephant Man, etc. Podoconiosis is a type of lower limb tropical elephantiasis distinct from lymphatic filariasis. Lymphatic filariasis affects all population at risk, whereas podoconiosis predominantly affects barefoot subsistence farmers in areas with red volcanic soil. Ethiopia is one of the countries with the highest number of podoconiosis patients since many people are at risk to red-clay soil exposure in many parts of the country. The aim of this review was to know the current status and impact of podoconiosis and its relevance to elephantiasis in Ethiopia. To know the epidemiology and disease burden, the literatures published by different scholars were systematically reviewed. The distribution of the disease and knowledge about filarial elephantiasis and podoconiosis are not well known in Ethiopia. It is relatively well studied in southern Ethiopia but data from other parts of the country are limited. Moreover, programmes that focus on diagnosis, treatment, prevention and control of filarial elephantiasis and podoconiosis are also non-existent even in endemic areas. Furthermore, the disease mapping has not been carried out country-wide. Therefore, in order to address these gaps, Ethiopian Ministry of Health needs to take initiative for undertaking concrete research and mapping of the disease in collaboration with stakeholders.

A case of late-stage lymphogranuloma venereum in a woman in Europe.

Lymphogranuloma venereum is caused by Chlamydia trachomatis serovars L1-L3. The third stage of the disease leads to chronic progressive lymphangitis. The first European case of elephantiasic enlargement of the female genitalia caused by C. trachomatis L2 serovar in decades is reported.

Conidiobolomycosis in a young Malaysian woman showing chronic localized fibrosing leukocytoclastic vasculitis: a case report and meta-analysis focusing on clinicopathologic and therapeutic correlations with outcome.

BACKGROUND: Conidiobolomycosis (also known as rhinoentomophthoramycosis) is a rare cutaneous/mucosal fungal infection seen mainly in the tropical rain forest regions of the world that can be associated with disfiguring facial elephantiasis, and rarely, death. OBJECTIVE: To present an exemplary case report and perform a systematic review of the world's literature to more accurately describe the natural history and the effect of therapy on outcome in conidiobolomycosis. METHODS: Case report and meta-analysis of published case reports and series of conidiobolomycosis to determine which clinical, pathologic, mycologic, and treatment factors impact on prognosis. RESULTS: We document delay in diagnosis of conidiobolomycosis in a young Malaysian woman, whose biopsy showed pathognomonic features-massive tissue eosinophilia and Splendore-Hoeppli phenomenon surrounding broad hyphae. These findings coexisted with granuloma faciale-like changes (fibrosing leukocytoclastic vasculitis) and lymphedema. Treatment with multiple antifungals was followed by complete resolution. For the meta-analysis, pooled data from 199 cases (162 with full outcome data) from 120 reports revealed a similar course for most cases: a disease affecting healthy young adults who present with progressive nasal symptoms (eg, nasal obstruction) and central facial swelling and show improvement or cure after surgical excision and/or treatment with one or more antifungal agents in 83%. Persistent-progressive facial disease occurred in 11%, and 6% died rapidly of fungal infection. Presentation with facial elephantiasis correlated with persistent-progressive rhinoentomophthoramycosis and a longer duration of disease before diagnosis (P = 0.02). Lethal infections were significantly associated with nonstereotypical presentation (eg, orbital cellulitis), visceral infection, absence of the Splendore-Hoeppli phenomenon, presence of comorbidities (eg, immunosuppression, hematolymphoid malignancy), infection with Conidiobolus incongruus or Conidiobolus lamprauges (not Conidiobolus coronatus), lack of response to amphotericin B, and female sex (all P ≤ 0.002). The few sensitivity studies performed demonstrated in vitro multidrug resistance of Conidiobolus species to most available antifungal agents. LIMITATIONS: Publication bias, reporting heterogeneity, and data deficits may affect results. CONCLUSIONS: Conidiobolomycosis should be included in the differential diagnosis of patients who present with nasal symptoms and painless centrofacial swelling. Massive tissue eosinophilia and Splendore-Hoeppli material coating thin-walled hyphae confirms the clinical diagnosis. The granuloma faciale-like histology found in this case can explain the onset of facial lymphedema by fibroinflammatory destruction of lymphatic vessels; the duration of disease and severity of inflammation likely predicts whether the lymphedema is reversible or not. Although rhinoentomophthoramycosis ostensibly responds in vivo to most available antifungal agents, routine culture and susceptibility testing is recommended to better define the efficacy of these therapeutic agents.

A case of elephantiasis nostras verrucosa treated by acitretin.

Elephantiasis nostras verrucosa is a rare disorder characterized by dermal fibrosis, hyperkeratotic, verrucous, and papillomatous lesions that result from both chronic filarial and nonfilarial lymphedema. Various treatment options have been reported for this disease. We present a 64-year-old man with erythrodermic psoriasis and elephantiasis nostras verrucosa in whom the lesions were resolved almost completely after acitretin treatment.

[Current wound care in patients with elephantiasis--third-stage lymphedema]. / Suvremeno lijecenje rana kod bolesnika s elefantijazom --trecim stadijem limfedema.

Lymphedema resulting from fluid accumulation due to impairment in the lymphatic system drainage leads to enlargement of the body part involved. If left untreated, in its third stage it results in elephantiasis. Elephantiasis is frequently accompanied by papillomatosis and lymphocutaneous fistulas with lymphorrhoea, erosions and ulcers, frequently with the loss of function in the respective part of the body. Unlike other chronic wounds, wound healing in lymphedema is highly dependent on the use of combined therapies because local treatment with modern supportive dressings and compression therapy with adhesive and non-adhesive short-stretch systems is only part of the complete treatment. This treatment also includes sub-bandage foamy materials, kinesitherapy with tapes (kinesiotaping), intermittent local application of high-pressure oxygen, breathing exercise, and manual lymph drainage and exercises.

Saxophone penis - An intriguing manifestation of gastrointestinal metastasis.

Genital elephantiasis is associated with sexually transmitted infections such as lymphogranuloma venereum. Here we present an unusual and rare non-venereal cause of Saxophone penis.

Podoconiosis: Clinical spectrum and microscopic presentations.

BACKGROUND: Podoconiosis is a skin Neglected Tropical Disease (skin NTD) that causes lymphoedema, and affects barefooted subsistence farmers in some tropical countries. The clinical presentation and histopathologic correlates of podoconiosis have been understudied. Here, we systematically document the clinical and histopathologic spectrum of podoconiosis. METHODS: This is a cross-sectional study in Durbete, Ethiopia from February 2018 to October 2019. Dermatologists performed a patient history, physical examination, filariasis test strip, and skin biopsy for histopathologic examination. The results were summarised and a descriptive statistical analysis and Wilcoxon rank sum test with continuity correction was done. RESULTS: We recruited 289 patients for the study, 178 (61.6%) had stage 1 or 2 podoconiosis, and 111(38.4%) stage 3 to 5 podoconiosis. 188 (64.1%) had a family history of podoconiosis. In 251 (86.9%) patients, both legs were affected by podoconiosis and in 38 (13.1%) only one leg was affected. 220 (77.5%) patients had warty lesions, 114 (39.4%) had nodules. The median number of episodes of Acute Dermato-Lymphangio-Adenitis (ADLA) reported by the patients in the last three months was 2 (interquartile range (IQR) 1-4). Increased episodes of ADLA were significantly associated with stage 3-5 podoconiosis (P = 0.002), while burning pain in the feet was more common in stage 1 or 2 podoconiosis. Stage 3-5 disease was histopathologically characterised by epidermal and dermal thickening, verrucous acanthosis, inflammatory cell infiltrates (predominantly lymphoplasmacytic), dilated and ectatic and a reduced number of lymphatic vessels, eccrine ductal hyperplasia, and sclerosis such as thickened collagen bundles. CONCLUSION: We provide a detailed description of the different clinical patterns, associated clinical findings and the histopathologic spectrum of podoconiosis at different stages of the disease. Our observations should serve as a guide to classifying patients with podoconiosis for prognostic assessment and treatment decision.

Elephantiasis nostras verrucosa on the buttocks and sacrum of two immobile men.

Though typically involving the lower extremities, elephantiasis nostras verrucosa (ENV) can occur in any area affected by lymphedema. Here we report two cases of ENV: one is a biopsy-proven case and the other is a clinically diagnosed case. Both occurred on the buttocks and sacrum of immobile, morbidly obese men who were persistently in the supine or seated position. Whereas classic ENV is not uncommon, this striking presentation on these unusual areas is quite rare.

Surgical debulking of podoconiosis nodules and its impact on quality of life in Ethiopia.

BACKGROUND: In Ethiopia, severe lymphedema and acute dermato-lymphangio-adenitis (ADLA) of the legs as a consequence of podoconiosis affects approximately 1.5 million people. In some this condition may lead to woody-hard fibrotic nodules, which are resistant to conventional treatment. We present a series of patients who underwent surgical nodulectomy in a resource-limited setting and their outcome. METHODS: In two teaching hospitals, we offered surgical nodulectomies under local anaesthesia to patients with persisting significant fibrotic nodules due to podoconiosis. Excisions after nodulectomy were left to heal by secondary intention with compression bandaging. As outcome, we recorded time to re-epithelialization after surgery, change in number of ADLA episodes, change in quality of life measured with the Dermatology Quality of Live Index (DQLI) questionnaire, and recurrence rate one year after surgery. RESULTS: 37nodulectomy operations were performed on 21 patients. All wounds re-reepithelialised within 21 days (range 17-42). 4 patients developed clinically relevant wound infections. The DLQI values were significantly better six months after surgery than before surgery (P<0.0001). Also the number of ADLA episodes per three months was significantly lower six months after surgery than before surgery (P<0.0001). CONCLUSION: Nodulectomy in podoconiosis patients leads to a significant improvement in the quality of life with no serious complications, and we recommend this to be a standard procedure in resource-poor settings.