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.

Benign atrophic papulosis (Köhlmeier-Degos disease): the wedge-shaped dermal necrosis can resolve with time.

BACKGROUND: Atrophic papulosis is a rare thrombo-occlusive disease, characterized by the appearance of multiple atrophic porcelain-white skin papules, with a surrounding erythematous rim, which are histologically consisting of wedge-shaped necrosis of the dermis. OBJECTIVE: It consists of two variants: (i) the benign atrophic papulosis (BAP) only involving the skin and (ii) the malignant atrophic papulosis (MAP) also involving several internal organs with a cumulative five-year survival rate of approx. 55%. While the probability of only having a BAP at onset is approximately 70%, increasing to 97% after 7 years of monosymptomatic cutaneous course, no close long-term follow-up of the development of the skin lesions has been reported. METHODS: We present a precise visual documentation of the evolution of the disseminated skin lesions in a female patient with BAP spanning over two decades. RESULTS: A considerable improvement and/or clinical resolution of the majority of the lesions disputing the scarring character of the atrophic porcelain-white skin papules has been detected. CONCLUSION: BAP not only exhibits an excellent prognosis, but resolution of lesions can also occur after a considerable period of time.

Hydrogel coated mesh decreases tissue reaction resulting from polypropylene mesh implant: implication in hernia repair.

PURPOSE: Use of polypropylene mesh (PPM) in hernia repair is associated with tissue reactivity. We examined, in a rat model, a novel non-biodegradable hydrogel coated PPM which may allow for decreased inflammation and a decreased foreign body reaction. METHODS: Through a dorsal midline incision, a 2 cm × 2 cm section of PPM (either coated or uncoated) was placed on the fascial surface 1.5 cm from the incision on the dorsal wall of Sprague-Dawley rats. At 2 and 12 weeks after placement, the PPM and surrounding tissue were harvested. A board-certified dermatopathologist examined H&E stained slides for fibrosis and foreign body reaction. In addition, tissues were stained for apoptotic cells, oxidative damage, macrophages, fibroblasts, neovascularization and metalloproteases. RESULTS: At 2 and 12 weeks, there was a greater than 95 % decrease in foreign body giant cells in coated PPM samples compared to uncoated; fibrosis was decreased by 50 %. At 2 and 12 weeks, oxidative damage, fibroblast accumulation, apoptosis and macrophages were significantly decreased in coated PPM samples compared to uncoated PPM. CONCLUSION: These results demonstrate that a non-biodegradable hydrogel coating of PPM led to significant reduction in foreign body reaction, oxidative stress and apoptosis compared to uncoated PPM in vivo, and suggest that this coating could be clinically useful in hernia repair.

Laparoscopy shows superiority over endoscopy for early detection of malignant atrophic papulosis gastrointestinal complications: a case report and review of literature.

BACKGROUND: The malignant form of atrophic papulosis (Köhlmeier-Degos disease) is a rare thrombo-occlusive vasculopathy that can affect multiple organ systems. Patients typically present with distinctive skin lesions reflective of vascular drop out. The small bowel is the most common internal organ involved, resulting in considerable morbidity and mortality attributable to ischemic microperforations. Determination of the presence of gastrointestinal lesions is critical in distinguishing systemic from the benign, cutaneous only disease and in identifying candidates for treatment. CASE PRESENTATION: We describe an 18 year old male who first presented with cutaneous atrophic papulosis but became critically ill from small bowel microperforations. He had an almost immediate and dramatic response to treatment. Prior to his presentation with acute abdomen he had upper and lower endoscopy showing areas of nonspecific patchy erythema. At laparotomy, innumerable characteristic lesions with central pearly hue and erythematous border were seen. PubMed was used for a literature search using the keywords malignant atrophic papulosis, Degos disease, endoscopy, laparoscopy and laparotomy. This search yielded 200 articles which were further analyzed for diagnostic procedures and findings. Among the 200 articles we identified only 11 cases in which endoscopy was performed. Results of endoscopy and laparotomy in our patient with malignant atrophic papulosis were compared to those in the literature. Endoscopy of the gastrointestinal tract has shown gastritis and non-specific inflammation whereas laparoscopy shows white plaques with red borders on the serosal surface of the small bowel and the peritoneum. From personal communications with other physicians worldwide, we identified three additional unpublished cases in which endoscopy revealed only minimal changes while laparoscopy showed dramatic lesions. From our experience the endoscopic findings are often subtle and nonspecific, whereas laparascopy or laparotomy will reveal pathognomic lesions on the serosal surface of the intestine. CONCLUSION: Our report contrasts the endoscopic and laparoscopic findings in malignant atrophic papulosis which suggest laparoscopy is the more powerful means of detecting gastrointestinal involvement. Imaging studies may serve as a key indicator of systemic progression. Based on our experience, laparoscopy should be performed when there is a high index of suspicion for gastrointestinal malignant atrophic papulosis, even if endoscopic examination is non-diagnostic or normal.

Follicular cutaneous squamous cell carcinoma: an under-recognized neoplasm arising from hair appendage structures.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) with no demonstrable point of epidermal origin is problematic as it raises consideration of metastatic SCC histologically. There are rare case reports and series of SCC arising from the wall of hair follicle structures. Such lesions have been termed follicular SCC (FSCC). OBJECTIVES: To investigate the clinicopathological features of FSCC. METHODS: We prospectively collected cases of follicular SCC over a 5-year period. Follicular SCC is defined as a cutaneous SCC deriving from a pre-existing hair follicle structure. Lesions were considered to represent 'hybrid' SCCs if an interfollicular epidermal origin was also demonstrated; SCCs with > 50% of the origin from interfollicular epidermis were excluded. Histological features and clinical information were evaluated. RESULTS: We identified 61 cases of follicular SCC arising in 60 patients from a database of 5212 cutaneous SCCs encountered over the same time period by the same authors. There were 49 pure follicular SCCs and 12 hybrid lesions. The male to female ratio was 44 : 16; the mean age was 74 years (range 44-93). Follicular SCC represents 1·2% of all primary SCCs. Biopsies of such lesions, if the appendage structure of origin is not represented, are histologically indistinguishable from metastatic SCC. CONCLUSIONS: Recognition of this under-reported form of SCC is essential if an inappropriate diagnosis of metastatic SCC, with potentially harmful and inappropriate therapy and investigation, is to be avoided.

Cutaneous melanoma arising from a cesarean delivery skin scar.

A 41-year-old pregnant African-American woman noticed rapid growth of her cesarean delivery skin scar beginning at 14-week gestation. Skin biopsy, which was performed at 31 weeks, revealed poorly differentiated cutaneous melanoma. At 34 weeks, she underwent repeat cesarean delivery with tumor excision, pelvic lymphadenectomy and abdominal wall reconstruction. Locally advanced disease and anatomical limitations prevented attainment of negative surgical margins. Despite adjuvant chemotherapy and radiation, she died 1 year after diagnosis. Deferring biopsy of a suspicious skin lesion during pregnancy may have delayed the diagnosis of melanoma in this case and possibly affected the long-term outcome.

miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions.

BACKGROUND: Expression of microRNAs (miRs) has been shown to be altered in many solid tumours and is being explored in melanoma. The malignant potential of some melanocytic lesions is difficult to predict. We hypothesised that characterisation of miR expression in borderline melanocytic proliferations would lead to the identification of a molecular profile that could be used with known prognostic factors to differentiate lesions with high malignant potential. METHODS: The miR expression profile of melanocytic lesions (benign naevi, malignant melanoma and borderline melanocytic tumours) was evaluated by real-time PCR. RESULTS: PCR analysis revealed primary cutaneous melanomas had an 8.6-fold overexpression of miR-21 and a 7.5-fold overexpression of miR-155 compared with benign naevi (P<0.0001). In situ hybridisation confirmed these results. miR-21 and miR-155 were significantly overexpressed within borderline lesions (P=0.0011 and P=0.0048, respectively). When borderline lesions were categorised by mitotic activity and Breslow thickness, miR-21 was associated with mitotic activity and miR-155 was associated with thickness (P<0.025). Among 14 patients with borderline lesions who underwent sentinel lymph node biopsy (SLNB), positive SLNB was associated with increased miR-21 and miR-155 in the primary lesion compared with lesions with a negative SLNB. CONCLUSION: MicroRNA expression profiles can be used to characterise atypical melanocytic lesions.

Atrophying tinea versicolor: a clinical and histological study of 12 patients.

BACKGROUND: We describe 12 patients with an atrophying dermatitis in whom the biopsy findings were compatible with tinea versicolor. DESIGN: We encountered 12 skin biopsies from 12 patients in whom a clinically atrophying dermatosis was associated with light microscopic (LM) evidence of atrophy and epidermal colonization by Pityrosporum sp. Formalin-fixed, paraffin-embedded tissue sections were cut at 5 microns and stained with H&E, alcian blue-PAS and PAS-diastase preparations. RESULTS: Five men and seven women aged 17-73 years in whom lesions characterized as atrophic plaques, patches or macules prompted clinical differential diagnoses including parapsoriasis or mycosis fungoides (MF), anetoderma, lupus erythematosus, and steroid atrophy. A LM examination showed epidermal colonization with pityrosporum hyphae and spores accompanied by variable epidermal and dermal atrophy characterized by rete-ridge effacement, subepidermal fibroplasia, pigment incontinence and elastolysis. CONCLUSIONS: Atrophying cutaneous lesions comprise part of the clinical spectrum of tinea versicolor for which we propose the term 'atrophying tinea versicolor'. The pathogenetic basis is unclear but could be the sequela of delayed type hypersensitivity and the release by T-helper lymphocytes of leukotrienes which perturb collagen metabolism and/or keratinocyte growth. Lesions may be mistaken clinically for MF or other atrophying dermatoses.

Tick mouth parts occlusive vasculopathy: a localized cryoglobulinemic vasculitic response.

BACKGROUND: The histologic hallmark of most arthropod bite reactions is a deep, wedge-shaped perivascular and interstitial infiltrate comprising lymphocytes, neutrophils, and eosinophils. METHODS: We present a case series of six patients in whom tick bite reactions, when examined microscopically, were found to mimic mixed cryoglobulinemic vasculitis. RESULTS: Though different in histology, clinically these lesions were indistinguishable from typical tick bite reactions. CONCLUSION: As five of our six biopsy specimens were found to still harbor retained tick parts, it is possible that the actual retention of tick parts was involved in evoking this localized cryoprecipitate reaction.

The spectrum of cutaneous lesions in rheumatoid arthritis: a clinical and pathological study of 43 patients.

INTRODUCTION: Rheumatoid arthritis (RA) is an idiopathic arthropathy syndrome that has a propensity to affect the small joints of the hands and feet with extra-articular manifestations comprising skin lesions, neuropathy, pericarditis, pleuritis, interstitial pulmonary fibrosis and a systemic polyarteritis nodosa (PAN)-like vasculitic syndrome. The most widely recognized skin lesion is the rheumatoid nodule. Other skin manifestations are poorly defined. MATERIALS AND METHODS: Using a natural language search of the authors' outpatient dermatopathology databases, skin biopsies from 43 patients with RA were selected for retrospective analysis in an attempt to define the dermatopathological spectrum of RA and its clinical correlates. RESULTS: The biopsies were categorized by the dominant histologic pattern, recognizing that in most cases there were additional minor reaction patterns. Palisading and/or diffuse interstitial granulomatous inflammation was the dominant pattern seen in 21 patients; the lesions included nodules, plaques and papules with a predilection to involve skin over joints. Besides interstitial histiocytic infiltrates and variable collagen necrobiosis, these cases also showed interstitial neutrophilia, vasculitis and pauci-inflammatory vascular thrombosis. The dominant morphology in 11 other patients was vasculopathic in nature: pauci-inflammatory vascular thrombosis, glomeruloid neovascularization, a neutrophilic vasculitis of pustular, folliculocentric, leukocytoclastic or benign cutaneous PAN types, granulomatous vasculitis, and lymphocytic vasculitis and finally occlusive intravascular histiocytic foci for which the designation of "RA-associated intravascular histiocytopathy" is proposed. Rheumatoid factor (RF) positivity and active arthritis were common in this group, with anti-Ro and anticardiolipin antibodies being co-factors contributing to vascular injury in some cases. Immunofluorescent testing in three patients revealed dominant vascular IgA deposition. In nine patients, the main pattern was one of neutrophilic dermal and/or subcuticular infiltrates manifested clinically as urticarial plaques, pyoderma gangrenosum and panniculitis. CONCLUSIONS: The cutaneous manifestations of RA are varied and encompass a number of entities, some of which define the dominant clinical features, such as the rheumatoid papule or subcutaneous cords, while others allude to the histopathology, i.e. rheumatoid neutrophilic dermatosis. We propose a more simplified classification scheme using the adjectival modifiers of "rheumatoid-associated" and then further categorizing the lesion according to the dominant reaction pattern. Three principal reaction patterns are recognized, namely extravascular palisading granulomatous inflammation, interstitial and/or subcuticular neutrophilia and active vasculopathy encompassing lymphocyte-dominant, neutrophil-rich and granulomatous vasculitis. In most cases, an overlap of the three reaction patterns is seen. Co-factors for the vascular injury that we believe are integral to the skin lesions of RA include RF, anti-endothelial antibodies of IgA class, anti-Ro and anticardiolipin antibodies.

Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.

INTRODUCTION: The diagnosis and classification of lymphocytic lobular panniculitis (LLP) has historically proven to be a difficult challenge. We encountered 32 cases of primary LLP which could be categorized as: 1) lupus erythematosus profundus (LEP) (19 patients); 2) an indeterminate group termed indeterminate lymphocytic lobular panniculitis (ILLP) (6 patients); and 3) subcutaneous T-cell lymphoma (SCTCL) (7 patients). OBJECTIVE: We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome. METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from paraffin-embedded, formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses. RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or cytopenias, and a clinical course not suggestive of lymphoma. Cases of SCTCL showed hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively. Cytopenia was seen in 4 LEP patients; 1 also developed fever. In LEP and ILLP, lesions resolved with hydroxychloroquine and/or steroid therapy, with recurrences following cessation of therapy. In the SCTCL group 4 developed hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic necrosis of the fat lobule and thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant fat necrosis or vasculitis. Germinal centers, dermal/subcuticular mucin deposition and an atrophying interface dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression, fever, and cytopenias, but lesions responded to hydroxychloroquine and/or prednisone therapy and death attributable to panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features. CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.

Sweet's syndrome in the setting of CD34-positive acute myelogenous leukemia treated with granulocyte colony stimulating factor: evidence for a clonal neutrophilic dermatosis.

BACKGROUND: Sweet's syndrome in the setting of hematologic dyscrasias can be categorized into paraneoplastic-associated SS, drug-induced SS, and SS with leukemia cutis. Apart from those cases demonstrating concomitant leukemic infiltrates, it has been surmised that SS is a reactive phenomenon induced by a specific cytokine milieu. METHODS: The authors present a patient with CD34+ acute myelogenous leukemia (AAML) who developed SS in the setting granulocyte colony stimulating factor (GCSF) therapy. Routine light microscopy and molecular studies were carried on the patient's skin biopsy specimen and post-treatment marrow. An X inactivation assay for clonality was employed. RESULTS: Routine light microscopic examination revealed differentiated myeloid precursors including myelocytes and metamyelocytes within the subcutis; myeloblasts were not identified. In addition, in the overlying skin, features typical of SS were observed. The neutrophils demonstrated dysplastic features including hypolobation compatible with a Pseudo Pelger-Huet anomaly. X inactivation studies showed clonality both within her post-treatment marrow and skin biopsy specimen. CONCLUSIONS: Sweet's syndrome developing in CD34+ AML patients following GCSF therapy likely reflects therapy induced differentiation of sequestered leukemic cells, hence indicative of a clonal neutrophilic dermatosis.

Giant cells in pyoderma gangrenosum.

It has been claimed that pyoderma gangrenosum (PG) lesions may contain granulomatous foci when associated with Crohn's disease. To test this assertion, we obtained clinical histories and archived cutaneous biopsies from 34 PG patients. Thirteen of these patients had inflammatory bowel disease (IBD). Immunostaining with PGM1, a macrophage marker, revealed well-formed giant cells with three or more nuclei in biopsies from 6 of 13 patients with IBD. Five of the 6 biopsies came from patients with Crohn's disease and one from a patient with ulcerative colitis. Two were peristomal. In the 21 patients who had PG without IBD, no giant cells were seen. Thus, PGM1+ histiocytic giant cells within a PG lesion may be indicative of associated IBD (p = 0.006), particularly Crohn's disease.

A causal role for parvovirus B19 infection in adult dermatomyositis and other autoimmune syndromes.

BACKGROUND: Infection with parvovirus B19 (B19) has been associated with connective tissue disease (CTD) stigmata, namely, a systemic lupus erythematosus (SLE)-like illness, seronegative polyarthritis resembling rheumatoid arthritis, and vasculitis. The dermatopathology and pathogenetic basis of such B19-associated CTD-like syndromes have not been elucidated. OBJECTIVE: We attempted to document persistence of the B19 genome in skin lesions of 7 patients with CTD-like symptomatology following B19 infection and to correlate systemic manifestations to dermatopathological findings. METHOD: In 7 prospectively encountered patients in whom history, clinical signs and/or serology supported a diagnosis of CTD in the setting of B19 infection, dermatopathological and clinical features were correlated. Parvovirus B19 viral genome was sought in skin tissue using the polymerase chain reaction (PCR). RESULTS: Two patients had clinical features diagnostic of myopathic dermatomyositis (DM), 1 of whom is still symptomatic 1.5 years after the onset of her illness, and the other has had typical clinical features of DM for a duration of 3.5 years. A 3rd patient with SLE remains symptomatic 4 years after the onset of her illness. A 4th patient has persistent seronegative symmetrical polyarthritis of 6 years' duration and cutaneous lesions of granuloma annulare (GA). The 5th patient has a 1.5-year history of debilitating polyarthritis and cutaneous lesions with overlap features of DM and subacute cutaneous LE (SCLE). The 6th patient has had a persistent folliculocentric necrotizing vasculitis for 3 years. The 7th patient has a 1-year history of microscopic polyarteritis nodosa (PAN) with cutaneous vasculitis and persistent active renal disease. In 4 patients, exposure to children with fifth disease immediately preceded the onset of their CTD. Parvovirus B19 infection was documented serologically in 6 patients with antibodies of IgG subclass in 6 and of IgM subclass in 1. Four of 6 patients questioned had a history of atopy. Skin biopsies from patients with clinical features of SLE or DM demonstrated an interface dermatitis with dermal mucinosis. A necrotizing vasculitis with epithelial pustulation was seen in 2 patients. Interstitial GA-like infiltrates were seen in 5 cases. Immunofluorescent (IF) testing revealed a positive lupus band test (LBT) and epidermal nuclear and vascular staining for IgG and C5b-9 in the SLE patient. One DM patient had a negative LBT in concert with C5b-9 deposition along the dermoepidermal junction (DEJ) and within blood vessels while the other showed endomysial vascular Cs5b-9 deposition. In all patients, skin biopsy material contained B19 genome, which was absent in the serum of 4 patients analyzed. Symptomatic relief followed immunosuppressive and immunomodulatory therapy with agents including prednisone, cyclophosphamide, hydroxychloroquine, non-steroidal anti-inflammatory drugs and etanercept, but no patient has had complete symptom resolution. CONCLUSIONS: Persistent B19 infection may be of pathogenetic importance in certain prototypic CTD syndromes, to which underlying immune dysregulation associated with a blunted IgM response to viral antigen may predispose. Anti-viral therapy might be worthy of consideration since traditional immunosuppressive therapy was unsuccessful in our cases.

Necrotizing eosinophilic folliculitis as a manifestation of the atopic diathesis.

BACKGROUND: Eosinophilic folliculitis (EF) is an idiopathic eruption of sterile pustules and papules involving the trunk, face, and extremities, associated in many cases with human immunodeficiency virus (HIV) infection. The classic histopathology is one of follicular-based, eosinophilic spongiosis with variable microabscess formation. We describe nine HIV-negative patients who manifested a novel form of pustular EF in the setting of atopy. MATERIALS AND METHODS: Paraffin sections of skin biopsies from ten patients, stained with hematoxylin and eosin and special preparations to evaluate for microbial pathogens, were examined. Detailed clinical histories and serologic studies were obtained. RESULTS: Among the clinical presentations in seven men, two women, and one girl (age range, 11-62 years) were ulcerative and/or nodular plaques mainly on the face and/or extremities, sometimes in an annular configuration. The clinical considerations included deep mycotic infection, ulcerative herpes, systemic vasculitis, Mucha Haberman disease, and pyoderma gangrenosum. All patients had a personal and/or family history of atopy. Co-existent medical illnesses included psoriasis, lupus erythematosus, and lymphoproliferative disease. One patient was on a calcium channel blocker, one on multiple antidepressants, and two on antihistamines, all of which are associated with immune dysregulation. All skin biopsies showed variable intra- follicular eosinophilic microabscesses, follicular necrosis, folliculocentric necrotizing eosinophilic vasculitis, marked degeneration of connective tissue fiber elements, and striking tissue eosinophilia, including flame figure formation and dermal eosinophilic abscesses. Apart from commensals, such as Pityrosporum and Demodex, microbial pathogens were not identified. CONCLUSIONS: The presentations differed from conventional EF by virtue of a strong association with atopy and by the presence of ulceration, nodule formation, follicular and dermal necrosis, and eosinophilic vasculitis. We propose the term "necrotizing eosinophilic folliculitis," and suggest that the basis of this novel form of EF is an unrepressed T-helper lymphocyte type 2 (Th2)-dominant response to various epicutaneous stimuli in patients with atopy, the prototypic immune dysregulatory state associated with a Th2-dominant cytokine milieu.

The cutaneous manifestations of human parvovirus B19 infection.

The prototypical cutaneous manifestations of human parvovirus B19 (B19) infection include a petechial eruption in a glove and stocking distribution, reticular truncal erythema, and the "slapped cheek" sign. An association with connective tissue disease (CTD) stigmata has recently been made. The clinical and dermatopathologic findings in 14 patients whose skin lesions were accompanied by serological evidence of B19 infection or documentation of B19 genome in lesional skin are presented. The authors encountered skin biopsy specimens from 14 patients who presented with skin eruptions accompanied by clinical signs or serology suggestive of antecedent B19 infection. Clinical findings were correlated to the light microscopic appearance of the lesions and the presence of B19 genome in lesional skin. The study group comprised 9 women, 3 men, and 2 boys. Eruptions characteristic of fifth disease, including the slapped cheek sign, reticulated truncal erythema, and acral petechiae, were present in 3 patients, 1 of whom later developed granuloma annulare. The other patients had atypical clinical presentations comprising an asymptomatic papular eruption (2), an eruption clinically resembling Sweet's syndrome (3), myopathic dermatomyositis (DM) (2), lupus erythematosus (LE)-like syndromes (2), and lower-extremity palpable purpura (2). Skin biopsy specimens in 12 cases showed interstitial histiocytic infiltrates with piecemeal fragmentation of collagen and a mononuclear cell-predominant vascular injury pattern. Other features included an interface dermatitis, eczematous alterations, and papillary dermal edema. Lesions with features of DM or LE also showed mesenchymal mucinosis, whereas a biopsied lesion of palpable purpura showed leukocytoclastic vasculitis (LCV). Immunofluorescent testing showed a positive lupus band test (LBT) with epidermal IgG and C5b-9 decoration in 1 patient with a systemic LE-like illness, whereas the DM patients had negative LBTs and vascular C5b-9 deposition typical for DM. Skin biopsy specimens from 11 patients, including those whose presentations resembled LE and DM, were positive for B19 genome. The dermatopathology of B19 infection suggests tissue injury mediated by delayed-type hypersensitivity, by antibody-dependent cellular immunity directed at microbial antigenic targets in the epidermis and endothelium, and by circulating immune complexes in the setting of LCV. These mechanisms appear to generate a clinical and histopathological picture that recapitulates that of CTD.