Histiocytoid neutrophilic dermatoses and panniculitides: variations on a theme

Requena et al, in their article titled "Histiocytoid Sweet syndrome," in 2005, established that the dermal infiltrate in some patients with Sweet's syndrome is composed of histiocyte-like immature myeloid cells, not polymorphonuclear leukocytes as is the norm. With this premise in mind, we report on 6 cases of inflammatory skin disease in which the common denominator was a dermal and/or subcutaneous infiltrate of histiocytoid myeloid cells in patients with new-onset cutaneous eruptions and systemic symptoms. The cases were diverse clinically and microscopically, fell short of the criteria necessary for a diagnosis of classical Sweet's syndrome, and were difficult to categorize at the outset. The systemic manifestations ranged from malaise alone to a combination of fever, chills, night sweats, and polyarthralgia. The clinical morphology of the cutaneous eruptions varied from being papulovesicular in 1 patient to mainly consisting of erythematous plaques and nodules in the remainder. The dermatologists' differential diagnoses included Sweet's syndrome in 3 cases, a drug eruption in 2, and other entities such as erythema nodosum and Well's syndrome. Biopsies in all cases revealed a dermal and/or subcutaneous infiltrate composed predominantly of mononuclear histiocytoid cells of myeloid origin. With the benefit of detailed clinicopathologic correlation, the cases were classified for the purpose of this report as follows: Sweet's-like neutrophilic dermatosis, histiocytoid (3 cases); subcutaneous Sweet's syndrome, histiocytoid (2 cases); histiocytoid neutrophilic dermatosis, unspecified (1 case). In addition, we describe a further instructive case that exhibited overlap with those in the series but proved ultimately to represent leukemia cutis. The spectrum of observations in this report supports and expands the original concept of histiocytoid Sweet's syndrome.     

Neutrophilic panniculitis

Neutrophilic (lobular) panniculitis (NP) is a very rare condition that belongs to the group of neutrophilic dermatoses. We report the case of a patient with NP and review the relevant literature. NP appears as a subcutaneous nodular eruption. Histology shows a lobular neutrophilic infiltrate. NP must be differentiated from other types of panniculitis, and also from the subcutaneous septal involvement that may occur in some cases of Sweet's syndrome and from erythema nodosum. NP is significantly associated with myelodysplasia. It is highly sensitive to oral steroid therapy.     

Subcutaneous sweet syndrome

Neutrophilic panniculitis encompasses a heterogeneous group of diseases histopathologically characterized by an inflammatory infiltrate in the subcutaneous fat mainly composed of mature neutrophils. This group of panniculitides includes alpha(1)-antitrypsin deficiency, infectious panniculitis, factitious panniculitis, subcutaneous Sweet syndrome, neutrophilic/pustular panniculitis associated with rheumatoid arthritis, erythema nodosum-like lesions of Beh?et disease, bowel bypass panniculitis, and iatrogenic panniculitis. This article reviews subcutaneous Sweet syndrome, which is a rare idiopathic panniculitis characterized by a dense neutrophilic infiltrate in the subcutis and is often related to hematologic malignancies. The relationship of subcutaneous Sweet syndrome and erythema nodosum is discussed as well as the differential diagnosis with other neutrophilic panniculitis.     

Early pancreatic panniculitis associated with HELLP syndrome and acute fatty liver of pregnancy

Pancreatic panniculitis represents a rare cutaneous disorder most commonly associated with acute or chronic pancreatitis or pancreatic carcinoma. We describe a case of a 17-year-old woman who presented with a 2-day history of erythematous patches involving her bilateral knees and tender, scattered red-brown nodules involving her bilateral anterior shins. She was seen during a hospitalization for emergent cesarean section and her hospital course was complicated by HELLP syndrome (defined by the presence of hemolysis, elevated liver enzymes, low platelet count), acute fatty liver of pregnancy and pancreatitis. The characteristic histopathologic findings, including ghost cells, fat necrosis and granular basophilic material with dystrophic calcification, appear in later lesions. In early lesions, as was shown in this case, a neutrophilic subcutaneous infiltrate raises a differential diagnosis including infection, subcutaneous Sweet's syndrome or atypical erythema nodosum. To our knowledge, this represents the first report of pancreatic panniculitis in association with HELLP syndrome and acute fatty liver of pregnancy. Early recognition is critical, as skin lesions may precede the development of pancreatitis. Often, as in our case, the effects of pancreatitis may be life threatening.     

A Case of Sweet's Panniculitis Associated with Spinal Metastasis from Prostate Cancer

Sweet''s panniculitis is a rare variant of Sweet''s syndrome in which neutrophilic infiltrate can be found either in the subcutaneous fat or in both the dermis and the subcutaneous tissue. Due to the rarity of this entity, the association between Sweet''s panniculitis and malignancies is inconclusive, but cases of Sweet''s panniculitis have largely been associated with hematological malignancies. Herein, we present a case of Sweet''s panniculitis accompanied by bone metastasis from prostate cancer. Clinicians should be aware that Sweet''s panniculitis may be associated with malignancies of solid organs.     

Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim treatment: first reported case

Neutrophilic panniculitis is an infrequent entity, considered by most authors as part of the ‘neutrophilic dermatosis’ spectrum. Few cases have been reported to be related with granulocyte colony‐stimulating factor (G‐CSF); we report a case of neutrophilic panniculitis and Sweet's syndrome lesions related with pegfilgrastim, a long‐acting G‐CSF. A 77‐year‐old woman with M2 acute myeloid leukemia was treated with chemotherapy as well as broad‐spectrum antibiotics and antifungal drugs because of febrile neutropenia. Ten days after a single dose of pegfilgrastim, she developed a limited number of purple plaques on the neck, left leg, both arms and several indurated and slightly mobile nodules on her forearms. Skin biopsy of a plaque showed a diffused dermal neutrophilic infiltrate with dermal edema. Biopsy of a nodule showed a lobular neutrophilic panniculitis without vasculitis. No foreign material was found in those biopsies. No organisms were detected in blood, urine or tissue cultures. She was started with prednisolone 40 mg once a day, with dramatic improvement within the next 2 days. This case is noteworthy for the simultaneous appearance of Sweet's syndrome and neutrophilic panniculitis and it is the first case of neutrophilic panniculitis associated with this drug, pegfilgrastim.     

Drug-associated histiocytoid Sweet's syndrome: a true neutrophilic maturation arrest variant

Histiocytoid Sweet's syndrome is a recently described entity which has clinical features identical to typical Sweet's syndrome but is distinguished by a dermal cellular infiltrate composed not of mature neutrophils but of immature granulocytes. Herein, we report a case of bone marrow granulocytic maturation arrest and a histological histiocytoid Sweet's-like reaction pattern following trimethoprim-sulfamethoxazole therapy.     

Lymphocytic infiltrate of the dermis preceding typical Sweet's syndrome

BACKGROUND: The histologic criteria for Sweet's syndrome consist in prominent oedema of the dermis and a diffuse infiltrate of numerous neutrophils with leukocytoclasis without vasculitis in the superficial and the deep dermis. Several comorbidities have been observed in patients with Sweet's syndrome, particularly hemo-proliferative diseases. PATIENTS: We report the cases of two men aged 60 and 75 years with Sweet's syndrome associated in one case with myelodysplasia and in the other with chronic lymphocytic leukemia. These two patients had typical edematous plaques highly evocative of Sweet's syndrome. However, histological examination revealed superficial and deep perivascular lymphocytic infiltrate in the dermis on 5 occasions before the typical neutrophilic dermatosis of Sweet's could be diagnosed after respectively 2 and 4 years of progression. DISCUSSION: Histological findings in Sweet's syndrome are characteristic and constitute a major diagnostic factor. However, these two cases show that a lymphocytic infiltrate can occur months or even years before the appearance of typical neutrophilic infiltrate in patients with Sweet's syndrome.     

Familial Sweet's syndrome in 2 brothers,both seen in the first 2 weeks of life

Sweet's syndrome (or acute febrile neutrophilic dermatosis) is a rare inflammatory disease that is characterized by fever, neutrophilia, and painful erythematous plaques that histologically show a dense dermal infiltrate of neutrophils without associated vasculitis. We describe 2 neonates (10 and 15 days of age) with Sweet's syndrome; to our knowledge, this is the first reported case of siblings with Sweet's syndrome.     

Acute febrile neutrophilic dermatosis (Sweet's syndrome) in a patient with hairy-cell leukemia

A case of hairy-cell leukemia that started with cutaneous lesions similar to those of acute febrile neutrophilic dermatosis (Sweet's syndrome) is reported. The patient had leukopenia and a recurrent eruption for a year prior to the diagnosis of the hematologic disorder. Bone marrow examination eventually demonstrated characteristic "hairy" cells with tartrate-resistant, acid-phosphatase activity. Biopsy of a cutaneous lesion suggested an abscess showing a dense neutrophilic dermal infiltrate with perivascular predilection. The findings of IgA, IgM, C3, and fibrinogen in vessel walls by immunofluorescence and vascular disruption by electron microscopy contribute additional evidence for an immunologic determinant in this instance of Sweet's syndrome. It is known that neutrophilic infiltrates of Sweet's syndrome may have a variety of clinical presentations. This is the second case of hairy-cell leukemia with which Sweet's syndrome was associated.     

Bullous Sweet's syndrome in congenital neutropenia: association with pegfilgrastim

Sweet's syndrome is an acute febrile neutrophilic dermatosis marked by attacks of painful, plaque-forming inflammatory papules accompanied by fever, arthralgias, peripheral leukocytosis, a diffuse dermal neutrophilic infiltrate, and prompt resolution of symptoms and lesions with glucocorticoid therapy. There are many reports of drug-induced Sweet's syndrome to various medications including all- trans -retinoic acid, carbamazepine, hydralazine, levonorgestrel/ethinyl estradiol, minocycline, trimethoprim/sulfamethoxazole, and granulocyte colony-stimulating factor. We describe the first known case of Sweet's syndrome induced by pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor with unique pharmacologic properties that may induce Sweet's syndrome in patients with no history of neutrophilic dermatoses associated with granulocyte colony-stimulating factor therapy.     

Acute infectious id panniculitis/panniculitic bacterid: a distinctive form of neutrophilic lobular panniculitis

Background: Lobular panniculitis encompasses lupus profundus, atypical lymphocytic lobular panniculitis, erythema induratum and subcutaneous Sweet’s syndrome, while septal panniculitis includes erythema nodosum and fibrosing dermal processes of burn out necrobiosis lipoidica and morphea profundus. Panniculitis may represent a sign of systemic disease and/or a modified immune response to hematogenously disseminated antigen. Methods: We describe 10 cases of sterile neutrophilic dominant lobular panniculitis that represented an id reaction to non‐tuberculous stimuli. Results: Four males and six females had sudden tender non‐ulcerated lower extremity nodules with preceding non‐tuberculous infectious triggers. Three also had upper extremity lesions. Biopsies showed dominant neutrophilic infiltrate with subcutaneous microabscesses (7), extravascular granulomatous infiltrates (5), thrombotic microangiopathy (5) and necrotizing vasculitis (5). Stains evaluating microbial pathogens were negative. Lesions resolved with antibiotic treatment and/or abscess drainage; no case recurred. Medical histories included atopic diathesis (4), primary antiphospholipid antibody syndrome (1), ulcerative colitis (1) and acute lymphocytic leukemia (1). Serologies showed polyclonal hypergammaglobulinemia, cold agglutinins and cryofibrinogens. Conclusions: We propose the term acute infectious id panniculitis for cases of neutrophilic lobular panniculitis triggered by non‐tuberculous infectious stimuli. This course may be self‐limited. Microvascular cofactors and/or procoagulant states may be pathogenetically important. Recognizing this entity may circumvent the need for an exhaustive evaluation for other causes of neutrophilic lobular panniculitis.     

Particular histological features of a case of Sweet's syndrome induced by G-CSF

BACKGROUND: Sweet's syndrome may occur during medullar aplasia, especially after treatment with exogenous growth factors such as G-CSF. In this context, Sweet's syndrome presents particular histological features that we detail in this observation. CASE REPORT: A 50 year-old man was treated for multiple myeloma with a mobilizating chemotherapy prior to autologous stem cell transplantation. Four days after the onset of G-CSF, he presented with a febrile generalized eruption of erythematous infiltrated lesions. Histological examination of a skin biopsy showed a neutrophilic infiltrate associated with atypical xanthomized histiocytes and vascular hyperplasia with marked endothelial turgescence. Treatment with a short cause of oral corticosteroids was efficient. DISCUSSION: The classical histological features of Sweet's syndrome consist in a dermal neutrophilic infiltrate with edema. In our patient, we noticed the presence of atypical histiocytes among the dermal neutrophilic infiltrate. These histiocytes are described in maculo-papular eruptions induced by G-CSF, and should not be confused with a malignant infiltrate associated with a hemopathy. Vascular hyperplasia may be related to the angiogenic properties of G-CSF. Knowledge of these histological features would enable clinicians and histologists to recognize the appropriate diagnosis.     

Sweet's syndrome revisited: a review of disease concepts

Sweet's syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by a constellation of symptoms and findings: fever, neutrophilia, erythematous and tender skin lesions that typically show an upper dermal infiltrate of mature neutrophils, and prompt improvement of both symptoms and lesions after the initiation of treatment with systemic corticosteroids. Hundreds of patients with this dermatosis have been reported. The manifestations of Sweet's syndrome in these individuals have not only confirmed those originally described by Dr Robert Douglas Sweet in 1964, but have also introduced new features that have expanded the clinical and pathologic concepts of this condition. The history, clinical characteristics, laboratory findings, associated diseases, pathology, and treatment options of Sweet's syndrome are reviewed. The evolving and new concepts of this dermatosis that are discussed include: (i) Sweet's syndrome occurring in the clinical setting of a disease-related malignancy, or medication, or both; (ii) detection of additional sites of extracutaneous Sweet's syndrome manifestations; (iii) discovery of additional Sweet's syndrome-associated diseases; (iv) variability of the composition and/or location of the cutaneous inflammatory infiltrate in Sweet's syndrome lesions; and (v) additional efficacious treatments for Sweet's syndrome.     

Efficacy of anti-interleukin-1 receptor antagonist anakinra (Kineret®) in a case of refractory Sweet's syndrome

Sweet's syndrome is a neutrophilic dermatosis characterized by fever, an elevated neutrophil count, and painful erythematous cutaneous lesions. Histopathological analysis reveals a neutrophilic dermal infiltrate. Systemic corticosteroid therapy remains the mainstay of treatment. We report the case of a 66-year-old male patient who had a 5-year history of Sweet's syndrome refractory to various conventional treatments. Anti-interleukin-1 receptor antagonist anakinra was initiated and this resulted in a dramatic clinical and biological improvement. Anakinra is a promising treatment for neutrophilic dermatoses and sheds light on the interleukin-1/inflammasome pathway as central in the physiopathology of neutrophilic dermatosis.     

Sweet’s Syndrome

Sweet's syndrome was originally described in 1964 by Dr Robert Douglas Sweet as an 'acute febrile neutrophilic dermatosis'. The syndrome is characterized by pyrexia, elevated neutrophil count, painful red papules, nodules, plaques (which may be recurrent) and an infiltrate consisting predominantly of mature neutrophils that are diffusely distributed in the upper dermis. In addition to skin and mucosal lesions, Sweet's syndrome can also present with extra-cutaneous manifestations. Sweet's syndrome can be classified based upon the clinical setting in which it occurs: classical or idiopathic Sweet's syndrome, malignancy-associated Sweet's syndrome and drug-induced Sweet's syndrome. Systemic corticosteroids have been considered the 'gold standard' for the treatment of patients with Sweet's syndrome; in addition, treatment with topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy. However, spontaneous resolution of the symptoms and lesions has occurred in several patients with Sweet's syndrome for whom disease-specific therapeutic intervention was not initiated and in some of the patients with drug-induced Sweet's syndrome after withdrawal of the dermatosis-causing medication. Oral therapy with either potassium iodide or colchicine typically results in rapid resolution of Sweet's syndrome symptoms and lesions; therefore, in patients with Sweet's syndrome who have a potential systemic infection or in whom corticosteroids are contraindicated, it is reasonable to initiate treatment with these agents as a first-line therapy. Indomethacin, clofazimine, dapsone, and cyclosporine have also been effective therapeutic agents for managing Sweet's syndrome. However, indomethacin and clofazimine appear less effective than corticosteroids, potassium iodide, and colchicine. Appropriate initial and follow-up laboratory monitoring is necessary when treating with either dapsone or cyclosporine because of the potential for severe adverse drug-associated effects. Systemic antibacterials with activity against Staphylococcus aureus frequently result in partial improvement of Sweet's syndrome lesions when they are impetiginized or secondarily infected. In some patients with dermatosis-associated bacterial infections, organism-sensitive specific systemic antibacterials have been helpful in the management of their Sweet's syndrome. Although patients with hematologic malignancy-associated Sweet's syndrome often receive cytotoxic chemotherapy agents and antimetabolic drugs for the treatment of their underlying disorder, these agents are seldom used solely for the management of the symptoms and lesions of Sweet's syndrome. The treatment of patients with Sweet's syndrome with either etretinate or interferon-alpha have been reported as single case reports; both patients had improvement of not only their Sweet's syndrome lesions, but also their associated hematologic disorder.     

A case of Sweet's syndrome developed after the treatment of herpes simplex infection in a metastatic breast cancer patient

BACKGROUND: Sweet's syndrome or acute febrile neutrophilic dermatosis is associated with several systemic diseases such as malignancies and infectious diseases. METHODS: We present a 34-year-old woman with Sweet's syndrome associated with both herpes infection and metastatic disease. RESULTS: Skin biopsy showed neutrophilic infiltrates in the dermis confirming the diagnosis of Sweet's syndrome. CONCLUSIONS: To our knowledge, this is the second case of Sweet's syndrome associated with herpes simplex infection in the literature. Further observations are required to determine the relationship between Sweet's syndrome and herpetic infection.     

Neutrophilic lobular (pustular) panniculitis associated with rheumatoid arthritis: a case report and review of the literature.

Rheumatoid nodules, which affect the subcutis around joints, are the most frequent specific cutaneous lesions of rheumatoid arthritis (RA). Panniculitis is a rarely reported and nonspecific complication of RA. We report a 42-year-old woman with seropositive RA who presented with a 2-month history of lower leg panniculitis. Biopsy of a leg nodule showed a lobular neutrophilic infiltrate with lipophages and central basophilic necrosis. In addition, focal changes of lipomembranous fat necrosis indicative of ischemic damage were identified at the margins of the lobular infiltrate. Neutrophilic lobular panniculitis is commonly detected in panniculitis secondary to bacterial infections, pancreatitis, and factitial causes. However, this pattern of panniculitis has also been reported in some cases of erythema nodosum-like lesions found in Beh?et disease or bowel bypass syndrome and in rare cases of seropositive RA. These reported histologic findings fall into the spectrum of neutrophilic vascular reactions described by Jorizzo and Daniels for RA-associated dermatoses. In view of these findings. RA and related neutrophilic dermatoses (e.g., Beh?et disease) should be included in the differential diagnosis of neutrophilic lobular panniculitis.     

Sweet's syndrome revealing relapsing polychondritis

Sweet's syndrome is extremely rare in relapsing polychondritis. We report a rare case of Sweet's syndrome revealing relapsing polychondritis. A 77-year-old man presented with fever, associated with respiratory symptoms and non pruritic, painful, erythematous, papules and plaques mainly on the arms and legs. Skin biopsy of the arm found a neutrophilic dermal infiltrate consistent with Sweet's syndrome. A month and a half after admission, the patient presented with ear chondritis and dysphonia. Biopsy of the ear cartilage found a significant perichondral inflammatory cells infiltrate. The diagnosis of relapsing polychondritis was established and a steroid treatment was instituted with a complete regression of the cutaneous signs and chondritis.     

Subcutaneous histiocytoid Sweet's syndrome in a patient with myelodysplastic syndrome and acute myeloblastic leukemia

Subcutaneous histiocytoid Sweet's syndrome is a rare variant of histiocytoid Sweet's syndrome (SS). We present a 68‐year‐old woman with subcutaneous histiocytoid SS in association with refractory myelodysplastic syndrome transformed to acute myeloblastic leukemia (AML), status post induction chemotherapy and with persistent blasts (50%) in the bone marrow and blood, accompanied with neutropenia. The patient presented to the emergency room with fever and altered mental status. Clinical examination revealed approximately 20 scattered 0.5–2 cm, pink to pink‐purple non‐tender firm nodules on the legs and left arm. The differential diagnosis included Sweet's syndrome (deep), leukemia cutis, infection, polyarteritis nodosa and erythema nodosum. Histopathologic examination of a biopsy from the left arm revealed a nodular infiltrate of neutrophils and histiocytoid mononuclear cells solely in the lobular compartment of the subcutaneous fat with focal areas of necrosis. Most cells in the infiltrate labeled with myeloperoxidase (MPO) including the histiocytoid cells. The cells were negative for CD34 and CD117. All special stains for microorganisms were negative. A diagnosis of subcutaneous histiocytoid SS was made. A subcutaneous histiocytoid SS should be suspected when a neutrophilic/histiocytoid panniculitis, occurring in the setting of myeloid disorders, is encountered and after exclusion of an infectious process and leukemia cutis.