Cutaneous vasculitis in the course of hematologic malignancies

BACKGROUND: In patients with hematologic malignancies, cutaneous vasculitis is an important manifestation which may be secondary either to the malignancy itself or to many frequent events in these patients such as infections or drug intake. OBJECTIVE: To assess the underlying events responsible for cutaneous vasculitis in patients with hematologic malignancies. METHODS: Twenty-three patients with hematologic malignancies who had a skin biopsy in a single institution between January 1990 and June 1995 disclosing vasculitis were included in this study. Clinical, biological and immunological data, infectious enquiry and drug exposure were reviewed. RESULTS: The 23 patients represented 22% of 95 patients with hematologic malignancies in whom 105 skin biopsies were done. A lymphoproliferative disorder was found in 12/23 (52%) and a myeloproliferative disease in 11/23 (48%). The cutaneous vasculitis developed concomitantly with the malignancy in 39%, before in 26% and after the diagnosis of malignancy in 35%. The hematologic condition seemed to be the sole cause for vasculitis in 61% of the patients while the vasculitis could be attributed to another mechanism than the hematologic malignancy itself in 39%. These consisted in infections, medication and mixed cryoglobulinemia in 13% each. CONCLUSION: Cutaneous vasculitis constitutes a symptom developing in association with hematologic malignancy and may follow, accompany and also precede the condition. However, search for other triggering factors such as infection, drugs and cryoglobulinemia is required since they are the culprits of the vasculitis in 39% of cases.     

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.     

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis

BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.     

Efficacy of low-dose methotrexate in the treatment of dermatomyositis skin lesions

A limited number of case series has indicated that methotrexate (MTX) might be a useful drug in the treatment of dermatomyositis (DM), a rare autoimmune disease involving the skin and muscles. However, these earlier studies mainly focused on the efficacy of MTX on DM muscular symptoms. To analyse the efficacy of MTX on skin lesions in DM, the records of 34 patients with DM seen between 2004 and 2009 were retrospectively analysed, and the DM skin disease activity at different time points was determined, with specific focus on cutaneous features using the validated Cutaneous Dermatomyositis Activity Index (CDASI) score. The lesional inflammation was scored in primary skin biopsies. Additionally, we performed a systematic review of the available literature. In our series, 11 patients with DM received MTX, and in 8 of them, MTX led to a significant reduction of the DM skin lesions. CDASI scores decreased from 15.7 to 6.4 (P < 0.01) within 2-3 months, supporting the effectiveness of MTX in skin disease in DM. The lymphocytic infiltrate in primary skin lesions of MTX responders was significantly more pronounced than that in nonresponders. These results indicate that MTX might be an effective drug to treat the cutaneous symptoms of DM, as measured by the validated CDASI. Interestingly, MTX responders histologically presented a significantly stronger lesional lymphocytic inflammatory infiltrate than did nonresponders. These findings suggest that the functional inhibition of lymphocyte migration in the skin might be an important mechanism of MTX in the treatment of DM.     

白塞病64例临床分析

目的：探讨白塞病的临床特点及实验室改变。方法：对64例BD患的临床及实验室资料进行统计分析。结果：口腔溃疡61例,外生殖器溃疡44例,眼部损害21例,皮肤损害33例,针刺反应阳性39例。首发症状以口腔溃疡最常见（42例）。6例并发心血管系统损害,5例并神经系统损害,1例并急性肾功能衰竭,1例并食道下段溃疡并出血;实验室检查有多项免疫学指标的异常,12例检测到自身抗体（12／40）;皮肤及粘膜组织活检病理改变均符合小血管炎症。结论：白塞病是累及全身多系统器官以血管炎改变为基础的免疫性疾病,皮质类固醇激素或激素并免疫抑制剂治疗有较好的临床疗效。     

Type I interferon-associated skin recruitment of CXCR3+ lymphocytes in dermatomyositis

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease of unknown origin affecting skin and muscles. Infiltrating autoreactive T lymphocytes are thought to play an important pathogenetic role, but it is unclear which mechanisms are involved in the recruitment of these cells. Recent studies provided evidence that a type I interferon (IFN)-driven immune response, including the recruitment of T cells via IP10/CXCR3 interactions, might be important for the generation of skin lesions of cutaneous lupus erythematosus (CLE), an autoimmune disease that shares some clinical and histopathological features with DM. We hypothesized that a similar mechanism might also be involved in the pathogenesis of DM skin lesions. METHODS: Skin biopsies of 23 donors (11 DM, 5 healthy controls, 7 CLE controls) were analysed by immunohistochemistry using monoclonal antibodies against CD3, CD4, CD8, CD20, CD68, CD123, the chemokine receptor CXCR3 and its ligand IP10/CXCL10, and the myxovirus-resistance protein A (MxA)-protein, which is a specific marker for type I IFNs. RESULTS: We detected strong expression of the MxA protein in all DM skin biopsies, indicating involvement of type I IFNs. Expression of MxA was closely associated with expression of the interferon-inducible protein IP10/CXCL10 and the recruitment of CXCR3+ lymphocytes. Plasmacytoid dendritic cells appear to be an important source of type I IFNs in DM. DISCUSSION: Our results support the hypothesis that lesional type I IFN signalling, induction of IP10 expression, and recruitment of potentially autoreactive T cells via IP10/CXCR3 interaction are involved in the pathogenesis of DM skin lesions.     

The spectrum of cutaneous granulomatous vasculitis: histopathologic report of eight cases with clinical correlation

Cutaneous granulomatous vasculitis is an uncommon histopathologic finding that has been associated with lymphoproliferative disorders, systemic vasculitis, autoimmune inflammatory diseases, and infection. To define further the concept of cutaneous granulomatous vasculitis and to emphasize its clinical importance, we reviewed biopsy material from 8 patients seen from 1985 through 1992. All biopsies showed evidence of blood vessel damage with fibrinoid change or hemorrhage (or both) and granulomatous inflammation in and around vessel walls. Special stains for microorganisms were negative in all cases. Associated medical disorders included neuropathy (2 patients), sarcoid-like disease (2), systemic vasculitis (1), lymphoma and suspected lymphoma (1 each), and associated herpes simplex virus (1). T-cell gene-rearrangement studies were negative in a patient with suspected lymphoma. Granulomatous cutaneous vasculitis is most commonly associated with lymphoma and systemic vasculitis. In selected cases, infection should be considered as an underlying cause.     

Adult Henoch-schönlein purpura in a patient with myelodysplastic syndrome and a history of follicular lymphoma

GOAL: To understand Henoch-Sch?nlein purpura (HSP) to better manage patients with the condition. OBJECTIVES: Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the criteria for diagnosing HSP. 2. Explain the association of malignancy and HSP. 3. Discuss the prevalence of HSP in adults. Henoch-Sch?nlein purpura (HSP) is a systemic leukocytoclastic vasculitis involving arterioles and venules most commonly in the skin, glomeruli, and gastrointestinal tract. In skin, it is associated with IgA deposition around dermal blood vessels. While an exact cause of HSP has not been elucidated, several processes have been implicated in its development, including infections; drugs; and allergic, rheumatologic, and neoplastic diseases. We present a 57-year-old woman with a history of follicular lymphoma who developed HSP likely associated with myelodysplastic syndrome. This case is clinically significant because the patient was thought to be in remission of her hematologic disease until her skin findings prompted further evaluation. Her diagnosis of HSP was based on clinical presentation with palpable purpura and abdominal pain, and was confirmed with biopsy and immunohistochemical analyses of purpuric papules demonstrating leukocytoclastic vasculitis and strong anti-IgA labeling in the dermal endothelial cells consistent with immunocomplex deposition. The occurrence of vasculitis and malignant disease in the same patient often is difficult to interpret, as some patients may exhibit both diseases independently and by chance, while others may have vasculitis as a paraneoplastic syndrome. We review cases of adult HSP associated with malignancy in the literature.     

Immunohistochemical findings in notalgia paresthetica

BACKGROUND: Notalgia paresthetica (NP) is a sensory neuropathy the pathogenesis of which is not yet completely elucidated. OBJECTIVE: The aim of this study was to investigate the histopathological changes in NP with special emphasis on cutaneous innervation. METHODS: Along with site-matched biopsies from 5 healthy individuals, lesional skin biopsies from 14 cases of NP and biopsies from contralateral nonlesional skin in 9 of these cases were stained with hematoxylin-eosin and Congo red. For immunohistochemical analysis, all samples were stained with two general neural markers (S-100 protein and protein gene product 9.5) and two neuropeptides (vasoactive intestinal polypeptide and substance P). RESULTS: Light microscopy was compatible with postinflammatory hyperpigmentation. Immunohistochemistry did not reveal a significant difference in the staining pattern of lesional skin and control tissue (p > 0.05). Although not reaching statistical significance, the percentage of cases which showed no staining was higher in the group of patients with more chronic NP. CONCLUSION: The finding of less immunohistochemical staining in cases with more chronicity could be of clinical importance and is worth investigating further.     

A Practical Approach to the Diagnosis,Evaluation, and Management of Cutaneous Small-Vessel Vasculitis

Cutaneous small-vessel vasculitis (CSVV) is a disorder characterized by neutrophilic inflammation predominantly limited to the superficial cutaneous postcapillary venules. CSVV may be idiopathic or may have a defined cause such as infection, medication, connective tissue disease, or malignancy. CSVV may also be associated with extracutaneous disease or systemic vasculitis. The most common clinical presentation of CSVV consists of symmetrically distributed palpable purpura of the lower extremities. In general, lesional skin biopsy samples should be examined with light microscopy and direct immunofluorescence for adult patients with suspected CSVV. A complete history, review of systems, physical examination, and selected laboratory studies also should be performed to assess for inciting causes or extracutaneous involvement of CSVV. Treatment varies and depends on the chronicity of CSVV, the severity of cutaneous involvement, and the presence or absence of both an underlying cause and extracutaneous involvement of CSVV. An isolated episode of CSVV associated with a known inciting factor may be managed by removal or treatment of the trigger, along with symptomatic measures. First-line systemic treatments for chronic, idiopathic CSVV include colchicine or dapsone, used singly or in combination. Recurrent, chronic, or severely symptomatic CSVV that does not respond to the aforementioned therapies may require initiation of an immunosuppressive agent such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, or rituximab.     

Pseudoporphyria associated with Relafen therapy

Various oral medications including nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with pseudoporphyria, although the pathogenetic basis has not been elucidated. A novel NSAID nabumetone (Relafen) has become popular because of its minimal gastrointestinal side effects. Its association with pseudoporphyria is not reported save for its listing in the Physician's Desk Reference (PDR) as a possible side effect. Biopsies of lesional skin from 4 patients manifesting blisters and erosions on the hands and face within 4 months of starting nabumetone were submitted for light microscopic and immunofluorescent (IF) studies. Histories and serology were obtained. Two patients had rheumatoid arthritis (RA), 1 had mixed connective tissue disease (MCTD), and 1 received diltiazem. All 4 had antinuclear antibodies. Characteristic clinical, light microscopic and IF features in the absence of elevated urine porphyrin levels confirmed a diagnosis of pseudoporphyria in all 4 patients. Biopsies in three patients showed features attributed to underlying connective tissue disease (CTD), including ectasia of the superficial vascular plexus, mild leukocytoclastic vasculitis, superficial and deep perivascular lymphocytic infiltrates with dermal mucinosis, granular deposition of IgM along the dermoepidermal junction indicative of a positive lupus band test, and of IgG and C5b-9 within keratinocytes. Nabumetone (Relafen) can provoke pseudoporphyria; an underlying CTD diathesis may be a predisposing factor.     

Routine vs extensive malignancy search for adult dermatomyositis and polymyositis: a study of 40 patients

OBJECTIVE: To identify potential risk factors and the yield of routine screens for early detection of malignancy associated with dermatomyositis (DM) and polymyositis (PM). DESIGN: Retrospective study of malignancies in all patients with DM or PM followed up between the years 1981 and 2000 and a review of the relationship of DM and PM to malignancy, the usefulness of various tests or examinations for malignancy search, and the patients' course. SETTING: Departments of internal medicine and dermatology in a teaching hospital. PATIENTS: Forty consecutive adult patients with DM (33 cases) or PM (7 cases). MAIN OUTCOME MEASURES: (1) Rate of false-negative results of routine workup and yield (percentage of positive results) of blind malignancy search and (2) comparison of 16 characteristics in patients with malignancy vs those without. RESULTS: Malignancy occurred in 16 patients: 13 with DM and 3 with PM. In all cases, the diagnosis of malignancy was made concurrently with or shortly after the diagnosis of DM or PM. Factors associated with malignancy were recruitment in the internal medicine department (P =.02), constitutional symptoms (P<.01), a rapid onset of DM or PM (P =.02), the lack of Raynaud phenomenon (P<.01), and a higher mean erythrocyte sedimentation rate (P<.01) and creatine kinase level (P<.01). Initial routine search failed to discover 4 malignancies, 3 of which were discovered at an advanced stage by more extensive investigations. The positive result yield of blind malignancy search was only 13% (11 of 87), but reached 28% (5 of 18) for blind abdominal-pelvic and thoracic computed tomographic scans. CONCLUSION: Extensive search for malignancy, particularly computed tomographic scans, may be warranted in at least a subset of patients with DM or PM and risk factors of malignancy.     

系统性红斑狼疮伴肌炎的临床研究

目的探讨系统性红斑狼疮(SLE)伴肌炎患者的临床特点及其意义。方法采用对照研究方法 ,检测了64例SLE伴肌炎患者和43例皮肌炎(DM)患者的血清肌酶、肌电图、肌肉活检等 ,并做统计学分析。结果SLE肌炎的发生率为35 5 % ,症状轻 ,有轻度肌萎缩 ;与DM比较肌无力不明显(P<0 01) ;未见吞咽困难 ;SLE伴肌炎患者病情活动发生率[75 %(48/64)]高于非肌炎组[43 9 %(29/66)] ,有显著性差异(P<0 01) ;肌酶有所升高 ,但升高幅度均不超过正常值的50 % ,与DM患者比较有显著性差异(P<0 01) ;肌电图肌炎检出率为74 4 %(32/43) ,与DM组81 4 %(35/43)比较无显著性差异(P>0 05) ;肌活检显示 :肌间质血管炎 ,淋巴细胞和组织细胞浸润明显 ;肌纤维灶性肿胀 ,匀质变性 ,横纹模糊 ,未见坏死断裂 ,病变轻微。结论SLE肌炎较为常见 ,与SLE活动相关 ,症状轻 ,肌酶升高幅度小 ;肌电图与DM无异 ;肌活检间质病变明显 ,肌纤维病变轻微 ,有明显的临床和病理特征而有别于DM。     

Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA

BACKGROUND: Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes. OBJECTIVES: To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs). RESULTS: We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA. CONCLUSIONS: Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.     

Interleukin-6 expression in the skin of patients with lupus erythematosus

Abstract It has been proposed that interleukin-6 may play a role in the pathogenesis of autoimmune diseases like lupus erythematosus. We have therefore investigated the immunoreactivity of IL-6 in 32 skin biopsies of 23 patients suffering from chronic discoid lupus erythematosus (n=16), subacute cutaneous lupus erythematosus (n=5) and systemic lupus erythematosus (n = 5) as well as in uninvolved skin (n = 6) and in normal skin from healthy volunteers (n = 3). Increased immunohistochemical staining was detectable in 14 of 26 biopsies from lesional skin. The remaining biopsies from lesional, non-lesional and normal skin displayed only minimal or no reactivity, but 8 out of 12 lupus erythematosus patients had been pretreated with local or systemic antiinflammatory drugs. Irrespective of the LE subtype, immunolabelling was generally most intense in the basal layer of the epidermis, with additional intense suprabasal staining in sections from 2 of 5 SLE patients. Preferential production of IL-6 in the lower parts of the epidermis was confirmed by RNA in situ hybridization. No correlation was found between the deposition of immuno-globulins and complement at the dermo-epidermal junction and IL-6 expression in keratinocytcs. These data suggest that IL-6 may be involved in LE although its exact role in the pathogenesis of the disease needs to be further elucidated.     

Cutaneous vasculitis in rheumatologic disease: Current concepts of skin and systemic manifestations

Cutaneous vasculitis may be limited to the skin, a manifestation of systemic vasculitis, or a sign of an important underlying disease state. A thorough and systematic approach is required for accurate diagnosis and evaluation of such patients to enable appropriate management of the vasculitis and any associated condition. Occasionally, cutaneous vasculitis is a manifestation or presenting sign of connective tissue disease, such as systemic lupus erythematosus, Sjögren syndrome, or another condition. Such patients are at risk for poor outcomes related to systemic manifestations of vasculitis, as well as increased severity of the underlying disease. Recognition of this important subset of patients with skin vasculitis enables appropriate workup and successful management.     

Histopathological evidence of small-vessel vasculitis within the skin and lungs associated with interstitial pneumonia in an adult patient with dermatomyositis

Dermatomyositis (DM) often has a poor prognosis, due to complications associated with malignancy or interstitial pneumonia (IP). It is uncommon to find histopathological small-vessel vasculitis within cutaneous lesions and pulmonary capillaritis in patients with DM. A 64-year-old woman was diagnosed with DM based on the presence of quadriparesis, typical heliotropic rash, Gottron's papules, increased serum levels of muscle enzymes and typical muscle biopsy findings. She also had associated IP, which subsequently developed into a rapidly progressive condition. We found a high titre of Krebs von den Lunge (KL)-6 in her serum. Measurement of serum KL-6 level is widely accepted as a diagnostic test to monitor the activity of interstitial lung diseases. Histopathological examinations of the cutaneous and lung-associated features showed small-vessel vasculitis. We suggest that investigation of KL-6 levels in patients with DM and associated conditions should be carried out to determine if raised KL-6 levels are useful at predicting outcome or severity of various features.     

Granuloma annulare with a mycosis fungoides-like distribution and palisaded granulomas of CD68-positive histiocytes

We describe 3 unusual cases of granuloma annulare with multiple macular lesions in a distribution that simulated mycosis fungoides in patients with no associated underlying diseases. Repeated biopsies showed typical well-formed palisading granulomas and no evidence of an atypical lymphocytic infiltrate. There was no vasculitis, neutrophilic, eosinophilic, or interstitial infiltrate. The patients had no associated underlying diseases. Most of the histiocytes in the palisading granulomas were strongly positive for CD68. The lymphocytes were a minor component of the granulomatous inflammation and were predominantly CD8(+) T-cells. The findings in these cases add to the spectrum of previously defined granulomatous eruptions of the skin.