Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination.

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

Psoriasis With Eczematous Features: A Retrospective Clinicopathologic Study.

BACKGROUND: Dermatopathologists sometimes encounter patients with features of psoriasis vulgaris and additional changes of eczematous dermatoses. These cases are challenging to diagnose, and the clinical implications are unclear. In the age of targeted therapy, it is important to improve our understanding of these findings so that patients are managed appropriately. OBJECTIVE: To characterize the clinical characteristics, histopathological features, diagnostic workup, successful treatment, and outcomes of patients with overlapping histopathologic features of psoriasis vulgaris and eczema. METHODS: We conducted a retrospective chart review of 20 patients who had received the histopathologic diagnosis of psoriasis vulgaris with eczematous changes noted on skin biopsy. A database that included information about clinical characteristics, comorbidities, histopathological features, diagnostic workup, treatment modalities, and outcomes was created and analyzed. RESULTS: Twenty patients were included in this study, with an average age of 57.3 years. After clinicopathologic correlation, most patients were diagnosed with psoriasis (85%), and the remainder were determined to have an eczematous dermatitis. Thirty-five percent of patients were diagnosed with allergic contact dermatitis, either in combination with psoriasis (6 patients) or alone (1 patient). Topical glucocorticoids were the most common effective therapy used, and systemic therapies were required in nearly half of patients for successful treatment. CONCLUSION: This study offers insights into the clinically and histopathologically challenging diagnosis of psoriasis vulgaris with eczematous changes and offers the diagnostic term "eczematized psoriasis" to describe these patients. The presence of allergic contact dermatitis should be considered in these patients.

Papillary Dermal Elastolysis Secondary to Combination Nivolumab and Cabiralizumab Therapy: Histiocytes and Dermal Mucin as Clues to the Diagnosis.

ABSTRACT: Papillary dermal elastolysis has been described in the setting of experimental combination nivolumab and cabiralizumab immunotherapy. We report a third patient with distinctive, generalized atrophic macules that developed after a morbilliform eruption during a clinical trial for treatment of metastatic pancreatic adenocarcinoma. Histopathological findings demonstrated diminished elastic fibers in the papillary dermis, associated with a histiocyte-rich infiltrate and increased dermal mucin, features that should clue the dermatopathologist to this condition.

Practical Direct Immunofluorescence.

Direct immunofluorescence (DIF) remains a valuable tool that may be underused because of perceived challenges in the interpretation, limitations, and processing of DIF specimens. The aim of this review is to provide a practical guide for appropriately incorporating DIF in a variety of clinical diseases, such as autoimmune blistering disorders. In vasculitis, the role of DIF continues to evolve, particularly in the setting of IgA vasculitis. Although typically not indicated for the workup of connective tissue disease, DIF may be helpful in cases with negative serologies, nondiagnostic histologic findings, or scarring alopecia. Practical pearls for biopsy technique, specimen handling, and storage are also discussed.

What's New in Dermatopathology: Inflammatory Dermatoses.

Inflammatory skin diseases encompass a vast array of conditions. The field continues to expand and evolve with resurgence of conditions, through newly recognized medication adverse effects, and via more detailed descriptions of known dermatoses. The importance of clinicopathologic correlation and an up to date knowledge of dermatologic conditions cannot be overstated. This review focuses on an array of recent important developments in the histologic diagnosis of inflammatory conditions that affect the skin.

Eosinophils Among the Histological Features of Psoriasis.

"Eosinophils are absent in psoriasis" has been dogma for generations; yet, there is little published to support this statement. Two recent studies examining the presence of eosinophils in psoriasis came to contrasting conclusions. We reviewed skin biopsies from 50 patients with clinically confirmed cases of psoriasis vulgaris to characterize the histologic features, with a focus on the number of eosinophils in the dermis. We noted the presence of eosinophils in nearly half of our study population (n = 23, 46.0%). There was no significant association between the presence of eosinophils and degree of spongiosis (P = 0.405). Eosinophil density ranged from 0 to 8 per tissue section. The mean average eosinophil density was 1.04 (range: 0-8) per tissue section. Among cases with eosinophils, there were 73.9% (n = 17/23) of cases with 1-2 eosinophils, and 26.1% (n = 6) with 3-8 eosinophils. Mild to moderate spongiosis was noted in the majority of cases (n = 48; 96.0%). Eosinophils were only present in psoriasis cases with evidence of spongiosis (n = 23; 47.9%). We conclude that eosinophils are not an uncommon finding in the dermis of psoriasis vulgaris, although the number is often few. The presence of eosinophils should not preclude a diagnosis of psoriasis, particularly if other histologic features are supportive.

Response of Lichen Planopilaris to Pioglitazone Hydrochloride

Lichen planopilaris (LPP) is a cicatricial alopecia that often causes permanent hair loss. Pioglitazone, a peroxisome proliferator activated receptor-gamma (PPAR- γ) agonist, has demonstrated immunomodulatory properties that may offer an effective treatment modality. This retrospective analysis describes 23 patients with LPP treated with adjunctive pioglitazone. Most (18/25) demonstrated significant reduction in patient-reported symptoms and clinical signs of inflammation. No adverse effects were reported. J Drugs Dermatol. 2019;18(12):1276-1279.

Systemic lupus erythematosus and antineutrophilic cytoplasmic antibody-associated vasculitis overlap syndrome complicated by subarachnoid hemorrhage: case-based review.

Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) overlap syndrome is an inflammatory disorder with a mixed presentation that is characterized by clinical features of both SLE and AAV. Although renal disease predominates, any organ system in the body may be affected. Neurologic manifestation in patients with SLE-AAV overlap syndrome is rare and has only been previously documented as cerebral ischemia. We report a patient with SLE-AAV overlap syndrome diagnosed based on clinical, serologic and biopsy-proven histologic findings who presented with subarachnoid hemorrhage (SAH) secondary to ruptured right anterior cerebral artery aneurysm. To the authors' knowledge, this is the first reported case of SLE-AAV overlap syndrome diagnosed in a patient with a SAH due to an intracranial aneurysm. Neurologic involvement in patients with SLE-AAV overlap syndrome is uncommon and has not been well-studied. Clinicians who encounter patients with neurologic signs that present with symptoms and a serologic profile that correspond to both SLE and AAV criteria, should consider the association between SLE-AAV overlap syndrome and a hemorrhagic stroke, specifically SAH.

Unusual eruption in association with sorafenib: a case of acquired perforating dermatosis, reactive perforating collagenosis type.

The term, acquired perforating dermatoses (APD), represents a group of skin conditions that develop in adulthood and are characterized by transepidermal elimination of dermal connective tissue. This appears clinically as a papulonodule with a keratotic core. Although APD is typically associated with diabetes mellitus, chronic renal failure, and several other conditions causing generalized pruritus, there have been reports in the literature describing an association of APD with select drugs including sorafenib. We present a case of acquired perforating dermatosis in a patient with HIV and hepatocellular carcinoma undergoing treatment with sorafenib.

Cutaneous Crohn disease without gastrointestinal involvement in a 9-year-old boy.

Cutaneous Crohn disease (CCD) is a rare dermatologic manifestation of Crohn disease and is defined as noncaseating, granulomatous skin lesions noncontiguous with the gastrointestinal tract. It most commonly affects the skin of the legs, although genital CCD is the most common presentation in children. Diagnosis of CCD is made by a combination of clinical and histopathological findings. Therapeutic options include topical, intralesional, and systemic corticosteroids as well as topical and systemic immunosuppressants and immunomodulators. Surgical excision may be considered for refractory cases. We report CCD in a 9-year old boy with penile swelling, granulomatous cheilitis-like lesions, and perianal plaques.

Segmental stiff skin syndrome (SSS): A distinct clinical entity.

BACKGROUND: Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. OBJECTIVE: We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. METHODS: This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. RESULTS: Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. LIMITATIONS: This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. CONCLUSIONS: We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features.

Nonbullous neutrophilic lupus erythematosus: a newly recognized variant of cutaneous lupus erythematosus.

BACKGROUND: Neutrophils in the setting of systemic lupus erythematosus (SLE) are commonly associated with bullous disease. Rare cases of nonbullous neutrophilic lesions have been reported in patients with SLE. OBJECTIVE: This study used clinical and histologic findings of 4 patients to further define the newly emerging entity of nonbullous neutrophilic lupus erythematosus (LE). METHODS: We reviewed the clinical and pathological findings of 4 patients with known SLE who developed urticarial papules, plaques, subcutaneous nodules, or a combination of these. RESULTS: All patients were women with established SLE. Histopathological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, and variable vacuolar alteration along the dermoepidermal junction. Direct immunofluorescence study results in two patients were positive for C3, IgG, and IgM along the basement membrane zone. One patient also presented with neutrophil-rich lupus panniculitis. All clinical lesions resolved with immunomodulating/immunosuppressive agents. LIMITATIONS: This study was limited by the small number of cases. CONCLUSIONS: Nonbullous neutrophilic LE is an important entity to consider in the differential diagnosis of neutrophil-mediated eruptions. In addition, the histologic finding of neutrophils in the setting of lupus should alert one to the possibility of systemic disease.

Rhabdomyomatous mesenchymal hamartoma presenting on a digit.

Rhabdomyomatous mesenchymal hamartoma is a rare dermal lesion comprised of skeletal muscle, adipocytes and collagen. The vast majority has been described in very young patients on the head and neck. To our knowledge, there are only two reports of rhabdomyomatous mesenchymal hamartoma outside the head and neck region. Both of those lesions were located in the perianal area. We describe a rhabdomyomatous mesenchymal hamartoma in a 36-year-old man located on the great toe. Although rhabdomyomatous mesenchymal hamartoma is uncommon, it is important to be aware of this entity, its possible association with congenital syndromes and its potential for localization outside of the head and neck region.

Dermatopathology for the surgical pathologist: a pattern-based approach to the diagnosis of inflammatory skin disorders (part II).

The accurate diagnosis of inflammatory conditions in dermatopathology requires integrating the histopathologic findings with the clinical features. This second part of a 2-part review of inflammatory cutaneous conditions presents a pattern-based approach to the diagnosis of dermatologic disorders and reviews the salient clinical and histologic features.

Intravascular cytotoxic T-cell lymphoma: A case report and review of the literature.

Intravascular lymphoma (IVL) is a rare subtype of extranodal diffuse large B-cell lymphoma in the World Health Organization classification. Although the majority of cases are of B-cell lineage, cases of IVL with a T-cell phenotype and, rarely, histiocytic and natural killer (NK)-cell phenotypes have been reported. We report a case of T-cell IVL with a cytotoxic phenotype. A 62-year-old male presented with erythematous patches and plaques on the lower extremities, and a biopsy revealed IVL with an activated cytotoxic phenotype (CD56(+), perforin+, granzyme B+, TIA-1+, CD3epsilon(+), CD20(-), CD4(-), CD8(-), CD5(-), and T-cell receptor [TCR] betaF1(-)), consistent with either NK-cell or T-cell origin. TCR gene analysis showed a monoclonal T-cell population, supporting the diagnosis of a T-cell IVL. Although the patient's skin lesions were refractory to combination chemotherapy and salvage chemotherapy regimens, there has been no evidence of disease progression in 24 months of follow-up.