Therapeutic Approach in Pigmented Purpuric Dermatoses-A Scoping Review.

Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes. While generally benign, these dermatoses can be persistent and aesthetically bothersome. Key clinical features include red to brownish patches with a distinctive "cayenne pepper" appearance, predominantly localized on the lower extremities, particularly the shins. Subtypes include Schamberg disease, Majocchi's disease, Gougerot-Blum disease, Ducas and Kapetanakis pigmented purpura, and lichen aureus. Diagnosis relies primarily on clinical evaluation of skin lesions, with biopsy as a confirmatory tool. Although the exact cause of PPD remains unclear, capillary fragility and red blood cell extravasation are implicated. Treatment strategies for PPD aim to alleviate symptoms, considering the generally benign and chronic nature of the condition. As there is no standardized treatment, various methods with varying efficacy are employed. After searching SCOPUS and PubMed databases, we assessed 42 original articles to present current knowledge regarding therapy of PPD. This review will compare treatment approaches specifically in Schamberg disease and other manifestations of pigmented purpuric dermatoses.

A Rare Skin Rash: Linezolid-Induced Purpuric Drug Eruption without Vasculitis in a Puerto Rican Man.

BACKGROUND Cutaneous adverse drug reactions are the skin's response to a systemic exposure to drugs. Linezolid is an oral oxazolidine used to treat methicillin-resistant Staphylococcus aureus infections. Even though it has well-known adverse effects, purpuric cutaneous adverse drug reactions to linezolid have been scarcely described. This report is of a Puerto Rican man in his 80s who developed an extensive purpuric drug eruption secondary to linezolid use. Clinicians should be aware of this phenomenon, since prompt identification and discontinuation of the agent are essential for recovery. CASE REPORT An 89-year-old Puerto Rican man was given oral linezolid therapy for healthcare-associated pneumonia and developed a widespread, purpuric cutaneous eruption 5 days into therapy. His condition prompted immediate discontinuation of the drug. Forty-eight hours after stopping the medication, he visited the Emergency Department. Abdominal punch biopsy revealed a superficial and perivascular lymphocytic infiltrate with dermal eosinophils, a pathologic finding consistent with a purpuric drug eruption. This allowed for a timely diagnosis, exclusion of other mimickers, such as cutaneous vasculitis, and effective management. CONCLUSIONS Cutaneous adverse drug reactions to linezolid have been scarcely reported in the literature. Due to the low incidence of this manifestation, the identification of the causative agent and accompanying treatment may be delayed. Mainstays in therapy are avoidance of the offending agent and treatment with corticosteroids, antihistamines, barrier ointments, and oral analgesics. Primary healthcare providers should be aware of linezolid-induced cutaneous manifestations, diagnostic clues, and treatment options so they can rapidly identify and effectively treat such complications.

Vulvar Lichen Planus Presenting as Chronic Vulvar Purpura.

Background: There is a broad spectrum of vulvar pigmented lesions that differ based on their histopathological and clinical features. Chronic vulvar purpura is a rare entity, associated with a broad morphological spectrum, from lichen aureus, Zoon's vulvitis, pigmented purpuric dermatosis and with lichen planus as in our case. Case presentation: In this article we discuss a case of an 86-year-old white woman with hyperpigmentation on her upper vulva, next to the introitus, with complaints of urine incontinence. Biopsy revealed subepithelial stromal lichenoid inflammatory infiltrate containing plasma cells, lymphocytes and some neutrophilic granulocytes as well as dilated and congested vessels. Hemosiderin deposits and erythrocyte extravasation were found. There was evidence of hyperkeratosis with hyper granulosis and erosions. Spongiosis was also noted. Few melanocytes were identified with no sign of malignancy. These findings correlate with the diagnosis of vulvar lichen planus. Conclusions: Chronic vulvar purpura is a clinical term used for different chronic inflammatory dermatoses presenting as red bluish or violaceous discolorations on the vulva, often associated with cayenne-pepper-like speckling. Considering a great overlap of possible diseases, the final diagnosis could be challenging. It is important to exclude a melanocytic tumour in these cases.

Granulomatous pigmented purpuric dermatosis: Clinical and histopathologic findings in a series of nine cases.

We report the largest case series to date of granulomatous pigmented purpuric dermatosis (GPPD), a rare variant of pigmented purpuric dermatoses (PPD). GPPD can cause diagnostic difficulties as it can be mistaken clinically and histopathologically with numerous inflammatory and infectious dermatoses or even cutaneous T-cell lymphoma. We compared the histopathological findings of nine cases of GPPD with a control group consisting of 10 randomly selected PPD of other subtypes. GPPD seems to predominantly affect the lower extremities of adult male patients; a clear association with hyperlipidemia or other systemic conditions could not be confirmed. Histopathologically, GPPD is characterized by a dermal histiocyte-rich interstitial infiltrate with or without granuloma formation, thickened capillaries, extravasated erythrocytes, and/or hemosiderin deposits. In contrast to other forms of PPD, the inflammatory infiltrate of GPPD can extend to the mid or deep dermis and the admixed lymphocytic infiltrate is mainly composed of CD8+ T-cells.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Pigmented purpuric dermatoses versus purpuric mycosis fungoides: Clinicopathologic similarities and new insights into dermoscopic features.

BACKGROUND: The diagnosis of purpuric mycosis fungoides (PMF) is often challenging to be clinically differentiated from inflammatory diseases such as pigmented purpuric dermatosis (PPD). Dermoscopy as a non-invasive method can be employed for the visualisation of features invisible to the naked eye. OBJECTIVES: This study aimed to survey the dermoscopic findings of PMF in comparison with PPD. METHODS: Forty-one patients with an established diagnosis of PMF (n = 28) and PPD (n = 13) were prospectively recruited. Dermoscopic images were taken by FotoFinder Medicam 1000 (FotoFinder Systems GmbH, Bad Birnbach, Germany). RESULTS: Characteristic dermoscopic patterns consisting of fine short linear vessels (35.7%, P = 0.017) and spermatozoa-like structures (50%, P = 0.014) were found to be significantly more common in PMF lesions, while PPD lesions were typified by erythematous globules (76.9%, P = 0.01), in the background colour of dull red (61.5%, P = 0.01) and reticular pigmentation (61.5%, P = 0.044). CONCLUSIONS: This study showed the usefulness of dermoscopy for the diagnosis of PMF and PPD cases. Studies with long-term follow-up are needed to affirm the value of these dermoscopic patterns in the differentiation between the two entities.

Angiokeratoma-like purpuric palmar nodules following chemotherapy.

We describe a patient with leukemia undergoing chemotherapy who developed painful purpuric nodules of the digits. These findings were concerning for endocarditis (clinically) and angiokeratomas on gross histology. After extensive evaluation, we report the development of painful purpuric nodules as a likely side effect of the patient's therapeutic regimen (hydroxyurea, danorubicin, cytarabine, and methotrexate).

Cutaneous Polymer-Coating Embolism After Endovascular Procedures: Report of Two Cases and a Literature Review.

ABSTRACT: Different hydrophilic and hydrophobic polymers are used as lubricious coatings to reduce vascular traumas in minimally invasive percutaneous procedures. Although they are usually very safe, there is still a risk of serious complications in patients undergoing such procedures, mostly derived from the devices' coating detachment and systemic embolization. The lungs are the most common organ involved, followed by the central nervous system. Yet, cutaneous embolization is unusual, and only 19 cases are available in the literature. Most commonly, they present as asymptomatic retiform purpura on the lower legs, which tends to involve spontaneously. Correct clinical diagnosis is not suspected in most cases, being cholesterol emboly or vasculitis the preferred options. Time interval since surgical procedure and appearance of lesions vary widely but they generally start in the first few days. Histopathological identification of the embolus as bluish, amorphous intraluminal material in dermal vessels is diagnostic, but vasculitic signs are not present. We report 2 cases of skin lesions as the main manifestation of polymer embolization after endovascular surgical procedures. In both cases, biopsy allowed identification of embolized foreign material and lesions resolved without specific treatment.

Lichen aureus with pseudolymphomatous infiltrate.

Lichen aureus is a variant of pigmented purpuric dermatoses. The usual histopathology of lichen aureus is characterized by a subepidermal dense, band-like lymphocytic infiltrate, extravasated erythrocytes, and hemosiderin deposits. We report three patients with lichen aureus on the extremities with similar clinical, dermoscopic, and histopathological findings characterized by a dense band-like relatively deep dermal infiltrate accompanied by extravasation of erythrocytes and hemosiderin deposits occasioning a resemblance to a lymphoproliferative disorder.

Pigmented purpuric dermatosis: Ten years of experience in a tertiary hospital and awareness of mycosis fungoides in differential diagnosis.

BACKGROUND: Pigmented purpuric dermatoses (PPD) can clinically mimic many diseases. Histopathology provides a definitive diagnosis. The aim of the study is to reveal the features of patients with PPD and to determine the disease frequency in the differential diagnosis, especially mycosis fungoides (MF). METHODS: We retrospectively reviewed records of patients with PPD admitted to our hospital from January 2010 to May 2019. We studied the histopathological features of 127 patients, and performed pattern analysis on cases with a confirmed histopathologic diagnosis of PPD. Among the cases presenting with clinical features of PPD, but displaying different histopathological diagnoses, we focused on MF and tried to clarify the features of PPD-like MF. RESULTS: Overall, 389 patients were admitted to our hospital with PPD symptoms. Of them, 262 patients were diagnosed clinically and a histopathological examination was performed in 127 patients. Of 127, 87 were diagnosed with PPD, and in the remaining 40, non-specific features (9.4%), vasculitis (6.2%), pityriasis rosea (4.7%), MF (3.9%), suspected-MF (1.5%), and other dermatoses (%5.5) were detected. The biopsy findings of two patients showed PPD, but during follow-up, the diagnosis of MF was established. CONCLUSIONS: MF should be included in the differential diagnosis of PPD cases presenting with longstanding and widespread involvement.

The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series.

BACKGROUND: There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes. One is perniosis occurring in mildly symptomatic patients, typically children and young adults; the second is the thrombotic retiform purpura of critically ill adults with COVID-19. OBJECTIVES: To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19. METHODS: We compared the light microscopic, phenotypic, cytokine and SARS-CoV-2 protein and RNA profiles of COVID-19-associated perniosis with that of thrombotic retiform purpura in critical patients with COVID-19. RESULTS: Biopsies of COVID-19-associated perniosis exhibited vasocentric and eccrinotropic T-cell- and monocyte-derived CD11c+ , CD14+ and CD123+ dendritic cell infiltrates. Both COVID-associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein A (MXA), an established marker for type I interferon signalling in tissue. SARS-CoV-2 RNA, interleukin-6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, interleukin-6 and caspase 3; SARS-CoV-2 RNA was not seen. CONCLUSIONS: COVID-19-associated perniosis represents a virally triggered exaggerated immune reaction with significant type I interferon signaling. This is important to SARS-CoV-2 eradication and has implications in regards to a more generalized highly inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID-19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response. This allows excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation.

A detailed analysis of the distribution, morphology, and histopathology of complex purpura in hospitalized patients: A case series of 68 patients.

BACKGROUND: Purpura in inpatients commonly leads to dermatologic consultation. The differential diagnosis is broad and algorithms are intricate. OBJECTIVE: We evaluated inpatient consultations for complex purpura to document the most common diagnoses and to validate the true diagnostic utility of histopathology, clinical morphology, and distribution. METHODS: We reviewed a case series of 68 inpatients during a 4-year period with a dermatologic consultation for purpura and biopsy findings of vasculitis or microvascular occlusion. RESULTS: Key features of complex purpura are nonbranching (round) versus branching (retiform) morphology, dependent versus acral or generalized distribution, and leukocytoclastic vasculitis versus microvascular occlusion (with emphasis on depth of involvement). Dependent nonbranching purpura with only superficial vessels involved by leukocytoclastic vasculitis was most often due to IgA vasculitis or cutaneous single-organ small-vessel vasculitis. In contrast, deeper involvement by leukocytoclastic vasculitis was suggestive of systemic disease (eg, antineutrophil cytoplasmic antibody-associated vasculitis). Branching purpura was concerning, with greater than 90% sensitivity and specificity for microvascular occlusion and associated high mortality (≈50%). The majority of patients who died had acral branching lesions. LIMITATIONS: Small sample size, inpatients at a tertiary care center, and retrospective nature are some limitations. CONCLUSION: Nonbranching dependent purpura corresponded to leukocytoclastic vasculitis, with the most common diagnoses being IgA vasculitis or skin-limited small-vessel vasculitis; patients with deep involvement often had systemic diseases. In this series, branching purpura was due to microvascular occlusion rather than medium-vessel vasculitis, and had associated high mortality.

Cryoglobulinemic glomerulonephritis: clinical presentation and histological features, diagnostic pitfalls and controversies in the management. State of the art and the experience on a large monocentric cohort treated with B cell depletion therapy.

Cryoglobulinemia is defined by the presence of immunoglobulins having the following characteristics: forming a gel when temperature is <37 °C, precipitate in a reversible manner in the serum, and redissolve after rewarming. The presence of both polyclonal IgG and monoclonal IgM (type II), or of polyclonal IgG and polyclonal IgM (type III) identifies the mixed cryoglobulinemia (MC). The identification of the Hepatitis C virus (HCV) infection in most of the cases previously defined as "essential" represented a cornerstone in the understanding the pathogenesis of this condition. The picture of MC comprehends heterogeneous clinical presentations: from arthralgias, mild palpable purpura, fatigue to severe vasculitis features with skin necrotic pattern, peripheral neuropathy and, less commonly, lungs, central nervous system, gastrointestinal tract, and heart involvement. The kidney represents the most common organ presentation, and the presence of glomerulonephritis is a key element when considering prognosis. We discuss the clinical presentation and histological features, diagnostic pitfalls, and controversies in the management of patients with cryoglobulinemic glomerulonephritis, with a special focus on reporting our experience in treating patients with B cell depletion therapy.