Acquired cutis laxa secondary to acute generalized exanthematous pustulosis: A case report and mini-review of literature.

Cutis laxa presents as loose redundant skin folds and loss of dermal elastic tissue. Acquired cutis laxa (ACL) is characterized by later onset. It has been reported in association with various kinds of neutrophilic dermatoses, drugs, metabolic disorders, and autoimmune disorders. Acute generalized exanthematous pustulosis (AGEP) is usually classified as a severe cutaneous adverse reaction characterized by T cell-mediated neutrophilic inflammation. We previously reported a mild case of AGEP caused by gemcitabine in a 76-year-old man. Here, we report a case of ACL secondary to AGEP in this patient. He developed AGEP 8 days after gemcitabine administration. Four weeks after beginning chemotherapy, his skin had become atrophic, loose, and darkly pigmented in areas previously affected by AGEP. Histopathological examination revealed edema and perivascular lymphocytic infiltration but no neutrophilic infiltration in the upper dermis. Elastica van Gieson staining showed that the elastic fibers in all layers of the dermis were sparse and shortened. Electron microscopy showed elevated numbers of fibroblasts and altered elastic fibers with irregular surfaces. Finally, he was diagnosed with ACL secondary to AGEP. He was treated with topical corticosteroids and oral antihistamines. Skin atrophy decreased over 3 months. We summarize 36 cases (including our case) with ACL secondary to neutrophilic dermatosis. We discuss these clinical manifestations, causative neutrophilic disorders, treatments, and outcomes. The mean age of patients was 3.5 years. Five patients had an aortic lesion as systemic involvement. The most common causative neutrophilic disorders were Sweet syndrome (24 cases), followed by urticaria-like neutrophilic dermatosis (11 cases). There were no cases of AGEP except for our case. Although treatment for ACL secondary to neutrophilic dermatosis, such as dapsone, oral prednisolone, adalimumab, and plastic surgery were reported, ACL is generally refractory and irreversible. Our patient was considered reversibly cured due to the absence of continuous neutrophil-mediated elastolysis.

Myelodysplasia Cutis.

CONTEXT.­: Myelodysplasia cutis is an emerging concept in cutaneous neoplasia. Many of these cases were previously included under the umbrella of histiocytoid Sweet syndrome. However, with the advent of next-generation sequencing, cutaneous involvement by myelodysplastic syndrome is being increasingly recognized. OBJECTIVE.­: To review histiocytoid Sweet syndrome and myelodysplasia cutis and discuss our current understanding of these entities. Additionally, to discuss how next-generation sequencing can be applied in the evaluation of cutaneous infiltrates of immature histiocytoid cells. DATA SOURCES.­: The English-language literature from 2005 to 2023 on the topic of histiocytoid Sweet syndrome and myelodysplasia cutis was reviewed. CONCLUSIONS.­: Biopsy specimens showing infiltrates of histiocytoid, immature myeloid cells may represent cutaneous involvement by myelodysplastic syndrome. Close clinical correlation is recommended in these cases. Recent studies suggest that next-generation sequencing is useful in separating myelodysplasia cutis from true histiocytoid Sweet syndrome. This distinction has important implications for patients.

Persistent Sweet syndrome post-hematopoietic stem cell transplantation heralding molecular relapse of myelofibrosis.

Persistent Sweet syndrome in a patient with history of myelofibrosis thought to be in remission post-hematopoietic stem cell transplantation leads to diagnosis of molecular relapse of myelofibrosis.

Neoplastic or inflammatory? A case report of Sweet syndrome with CD30+ cells in a patient with B-lymphoblastic leukemia.

CD30+ cells are typically part of lymphoproliferative disorders but can also be seen in inflammatory dermatoses. We present a case of 47-year-old man with a history of B-lymphoblastic leukemia (B-ALL) who presented with fever, leukocytosis, and papulonodular skin lesions, involving the extremities and trunk. A punch biopsy specimen demonstrated papillary dermal edema with a neutrophilic and histiocytic infiltrate extending into the subcutis. The infiltrate also harbored scattered large cells that were positive for CD30 and demonstrated the immunohistochemical profile of monocytes. A diagnosis of histiocytoid Sweet syndrome with CD30+ cells was made. The case is unique, demonstrating a combination of Sweet syndrome variants with subcutis involvement, histiocytoid morphology, and large CD30+ cells. A prior history of B-ALL and immunohistochemical profile of monocytes with immature morphology broadened the differential diagnosis and added to the diagnostic challenge.

Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature Syndrome: A Systemic Review.

BACKGROUND: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome is a rare, hereditary, autoinflammatory disease. However, there are few cases reported in the literature. Therefore, we conduct this systematic review to summarize current evidence. METHODS: We conducted a systematic search in July 2021 using 11 different electronic databases. The included articles were screened according to our inclusion and exclusion criteria and assessed using an appropriate quality assessment tool. Then, the relevant data were extracted and summarized in tables accordingly. Each step of the previous one was done by 3 independent reviewers, and the conflicts were resolved by discussion and sometimes by counseling a senior member. RESULTS: The final included studies were 18 articles with 34 cases (mean age = 8 years, male/female = 19/15). The most reported symptoms and signs were fever 97.1%, erythematous plaques 76.5%, arthralgia 67.6%, hepatomegaly 61.8%, violaceous hue 61.8%, lipodystrophy in extremities 53.1% in addition to low weight and height. Rare features were reported too. The laboratories were not specific, which may be explained by a systemic inflammatory response. Vasculitis was the dominant feature in the skin biopsy, whereas the calcification in the basal ganglia was a prominent sign in many cases. CONCLUSIONS: Fever, skin lesions, and systemic inflammatory response were the prominent features of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome. The clinical picture is the main guide in addition to the pathological findings. Mutation detection is the confirmatory test. Prednisolone is the most effective reported treatment for acute presentations in the literature.

Neutrophilic dermatoses - Pathomechanistic concepts and therapeutic developments.

Neutrophilic dermatoses are a group of clinically heterogeneous diseases characterized by infiltration of neutrophils in the affected tissue. Skin symptoms comprise a spectrum of wheals, papules, plaques, pustules, nodules and ulcerations often in combination with systemic symptoms. Although the pathogenesis of these diseases has not yet been elucidated in depth, broad pathophysiological and clinical overlaps exist with autoinflammatory syndromes. Additionally, recent years have shown the relevance of the signaling pathways of TNF-α, IL-1, IL-12/23 and IL-17 in neutrophilic dermatoses. In this review, we present four selected neutrophilic dermatoses, namely pyoderma gangraenosum, Sweet syndrome, generalized pustular psoriasis and Schnitzler syndrome, discuss pathophysiological aspects and specifically address novel therapeutic options derived from the most recent pathophysiological findings.

Photo-Induced Sweet Syndrome: A Case Report.

Sweet syndrome is a rare dermatologic condition frequently accompanied by fever and neutrophilia. Underlying triggers and etiology of the sweet syndrome remain elusive, although infection, malignancy, medications, and more rarely, sun exposure have been associated with its development. We present a case of a 50-year-old female who developed a painful, mildly pruritic rash on sun-exposed areas of the neck, arms, and legs. She also reported chills, malaise, and nausea upon presentation. Before developing the rash, she had preceding upper respiratory infection symptoms, used ibuprofen for joint pain, and had extensive sunlight exposure on the beach. Laboratory findings were significant for leukocytosis with absolute neutrophilia, elevated C-reactive protein, and elevated erythrocyte sedimentation rate. Skin punch biopsy demonstrated papillary dermal edema with dense neutrophilic infiltration. Further evaluation for hematologic or solid organ malignancy was negative. Following the administration of steroids, the patient demonstrated significant clinical improvement. While rare, ultraviolet A and B sunlight has been shown in rare situations to be associated with the development of the Sweet syndrome. The underlying mechanism for the development of photo-induced Sweet syndrome remains unknown. However, excessive sunlight exposure should be considered a potential cause when evaluating the underlying triggers for the development of the Sweet syndrome.

Elevated Intraocular Pressure in Periorbital Sweet's Syndrome.

A 66-year-old immunocompromised man presented with cellulitis around the left eye that was initially concerning for necrotizing fasciitis. Exam findings were remarkable for exquisite periocular tenderness with rigid, immobile eyelids resulting from severe erythema, edema, and induration. Given the concern for orbital compartment syndrome and a necrotizing infection, the patient was taken urgently to the operating room for debridement of the eyelid skin as well as an urgent lateral canthotomy and cantholysis. His eye exam revealed 360° of hemorrhagic chemosis, no relative afferent pupillary defect, and an ipsilateral elevated intraocular pressure of 35 mm Hg. No visual acuity measurement could be obtained secondary to the patient's altered mental status. His intraocular pressure normalized after treatment with antihypertensive drops and further extension of the canthotomy. Histopathological analysis showed extensive neutrophilic infiltrate of the dermis which was compatible with a diagnosis of Sweet's syndrome.

Neutrophilic dermatoses.

Neutrophilic dermatoses (ND) are a group of inflammatory skin conditions characterized by a neutrophilic infiltrate on histopathology with no evidence of infection. ND are classified based upon the localization of neutrophils within the skin and clinical features. Recent findings suggest that ND are due to two main mechanisms: i) a polyclonal hereditary activation of the innate immune system (polygenic or monogenic); or ii) a clonal somatic activation of myeloid cells such as encountered in myelodysplastic syndrome or VEXAS syndrome. ND belong to internal medicine as a great number of patients with ND suffer from an underlying condition (such as hematological malignancy, inflammatory bowel disease, auto-immune and auto-inflammatory diseases). ND are diagnoses of exclusion and physicians should always consider differential diagnoses, particularly skin infections. Here, we review the pathophysiology and classification of the main ND (i.e., subcorneal pustular dermatosis (Sneddon-Wilkinson Disease) and Intercellular IgA dermatoses, aseptic pustulosis of the folds, Sweet syndrome, neutrophilic eccrine hidradenitis, pyoderma gangrenosum, erythema elevatum diutinum, neutrophilic urticarial dermatosis and neutrophilic panniculitis), their clinical and histopathological features, and we highlight the investigations that are useful to identify ND-associated diseases and to exclude the differential diagnoses.

Sweet-like syndrome and multiple COVID arm syndrome following COVID-19 vaccines: 'specific' patterns in a series of 192 patients.

The two clinico-pathological patterns are 'Sweet-like syndrome' and 'Multiple COVID-Arm'. 'Sweet-like syndrome' presents clinically as erythematous and oedematous papules or plaques, sometimes developing vesiculation or bullae. Histology shows classical Sweet syndrome with a diffuse dermal neutrophilic infiltrate, or an infiltrate of histiocyte-like immature myeloid cells consistent with a histiocytoid Sweet syndrome. 'Multiple COVID-arm' is characterized by multiple large inflammatory plaques with histological analyses showing a perivascular and interstitial inflammatory infiltrate with eosinophils.

Neutrophilic Dermatoses in a Clinical Practice of Wound Care Professionals.

ABSTRACT: Diagnosing and treating neutrophilic dermatoses (NDs) in clinical practice can be challenging because of various presentations and stubborn treatment responses. Establishing a diagnosis is necessary, though, because many NDs are associated with underlying conditions, including malignancy. In this article, the authors provide information about Sweet syndrome, pyoderma gangrenosum, and other NDs and describe their clinical presentation, pathophysiology, diagnostic criteria, and associated conditions. The authors also present a case report describing the coexistence of two NDs and hidradenitis suppurativa in one patient and review the treatment modalities for those conditions.

A retrospective cohort study of infection risk in hospitalized patients evaluated for Sweet syndrome.

Sweet syndrome (SS) is divided into malignancy-associated, classical, and drug-induced subtypes. Features associated with SS, such as fevers, neutropenia, and cancer, are also high risk for serious infection. We aimed to describe hospitalized patients with a documented concern for SS on initial dermatologic evaluation, their risk of infection, and the impact of SS subtype on treatment and outcomes. We descriptively analyzed hospitalizations at The Ohio State University evaluated for SS by dermatology and performed a retrospective cohort analysis of malignancy-associated and non-malignancy-associated SS patients. Eighty-seven patient hospitalizations were evaluated for SS from 2012 to 2019. Thirty-one hospitalizations were complicated by neutropenia. Lesions in 12.9% (n = 4/31) of neutropenic hospitalizations were infected with Fusarium species (n = 2) or methicillin-resistant staphylococcus aureus (n = 2). One patient with fungal disease died within 30 days of hospitalization. Thirty-three patients were confirmed to have a final diagnosis of SS. In the confirmed SS cohort, malignancy was associated with greater overall dapsone use (p = .021), less initial (p = .046) and overall (p = .013) corticosteroid use, and fewer SS-related readmissions within one year (p = .020) and overall (p = .004). Corticosteroid treatment delay should be considered for a short period in neutropenic patients while excluding infection. Malignancy-associated SS patients were more frequently treated with dapsone and favorable outcomes were seen in cancer patients.

A case of recurrent acute febrile neutrophilic dermatosis in a patient with idiopathic cytopenia of undetermined significance.

This is the first report of recurrent acute febrile neutrophilic dermatosis in a patient with idiopathic cytopenia of undetermined significance. The patient progressed to acute myeloid leukaemia 4 months after onset.

Case Report: Rapid Response to Low-Dose Thalidomide in a Case of Severe Steroid Recalcitrant Erythema Nodosum Leprosum.

Erythema nodosum leprosum (ENL), or type 2 lepra reaction, presents with crops of evanescent, tender erythematous nodules accompanied by fever, arthralgia, malaise and organ-specific manifestations and is seen in borderline and lepromatous leprosy. The drugs approved for ENL include nonsteroidal anti-inflammatory drugs, systemic steroids, thalidomide and clofazimine. The management of ENL is challenging because long-term steroid use leads to steroid dependence. The present patient had severe steroid recalcitrant ENL with vesicular and pustular lesions mimicking Sweet's syndrome and was treated effectively with a low-dose thalidomide regimen (100 mg/d) as opposed to high dose (400 mg/d) recommended in literature. We discuss the patho-mechanics and clinical utility of a low-dose thalidomide regimen as an effective treatment option for ENL.