Increased nerve growth factor- and tyrosine kinase A-like immunoreactivities in prurigo nodularis skin – an exploration of the cause of neurohyperplasia

Neurotrophins and their receptors play an important role in cutaneous nerve development and reconstruction after injury. Recent developments indicate that this group of molecules not only exert a neurotrophic action, but are also involved in immune responses and inflammation. Prurigo nodularis is a skin disease characterized by neurohyperplasia and intense itch. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored by immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in the disease. In normal healthy volunteers and in uninvolved skin, NGF immunoreactivity was seldom seen in the basal layer of the epidermis or in the dermis. In prurigo nodularis skin, there was also very little NGF immunoreactivity in the epidermis. However, in the dermis, a huge number of cells showed an NGF-like immunoreactivity. In normal skin of healthy volunteers, only a weak staining for tyrosine kinase A (trkA) was seen in the epidermis, whereas in the dermis, there was no trkA staining seen at all. However, in the prurigo nodularis tissue, the hyperplastic nerves clearly showed trkA immunoreactivity, and it seemed that the staining was only present in the axons. By NGF and p75 NGF receptor double-labelling, both immunoreactivities showed weak staining in the epidermis and dermis of normal skin. However, in the dermis of prurigo nodularis, strong staining for both NGF and NGF receptor antibodies was seen. NGF receptor-immunoreactive nerves were more dense in areas where there were more NGF-immunoreactive cells. The results indicate that in prurigo nodularis skin, NGF is overexpressed, locally infiltrated inflammatory cells may be the source of this NGF, and NGF and its receptors may contribute to the neurohyperplasia of the disease.     

Light and electron microscopic immunohistochemical observations of p75 nerve growth factor receptor-immunoreactive dermal nerves in prurigo nodularis

Abstract Prurigo nodularis is an inflammatory skin disease characterized by neurohyperplasia. Neurotrophins and their receptors play a critical role in nerve growth, differentiation, maturation and maintenance, including cutaneous nerve fiber growth and innervation. They may also be responsible for events related to the growth and differentiation control of keratinocytes. To explore the exact distribution of the p75 low-affinity nerve growth factor receptor (p75 NGFr) in the cutaneous nerve components, p75 NGFr immunofluorescence as well as ultrastructural immunohistochemical studies were performed on prurigo nodularis lesional skin and normal human skin samples. The immunofluorescence results revealed that nerve fibers and bundles were increased in number and size in lesional upper dermis with stronger p75 NGFr immunoreactivity than in the corresponding normal tissue. At the ultrastructural level, a lot of nerve fibers clustered together in the prurigo nodularis dermal tissue. The axons were enlarged and branched, but the axons themselves seldom showed any NGFr immunoreactivity. The Schwann cell bodies were extended and irregularly shaped, and tended to separate into many branches enveloping the axons. The Schwann cell membrane showed strong p75 NGFr immunoreactivity. The perineurium cells also revealed strong p75 NGFr immunoreactivity. The Schwann cells inside the perineurium were less p75 NGFr-immunoreactive than those outside the perineurium. The membrane of certain basal keratinocytes showed NGFr immunoreactivity as well. The present results indicate that overexpression of p75 NGFr in Schwann cells and perineurium cells could contribute to the neurohyperplasia in prurigo nodularis. Received: 26 May 1998 / Received after revision: 3 September 1998 / Accepted: 17 September 1998     

Hair-cycle-associated remodeling of the peptidergic innervation of murine skin, and hair growth modulation by neuropeptides

As the neuropeptide substance P can manipulate murine hair growth in vivo, we here further studied the role of sensory neuropeptides in hair follicle biology by determining the distribution and hair-cycle-dependent remodeling of the sensory innervation in C57BL/6 mouse back skin. Calcitonin-gene-related peptide, substance P, and peptide histidine methionine (employed as vasoactive intestinal peptide marker) were identified by immunohistochemistry. All of these markers immunolocalized to bundles of nerve fibers and to single nerve fibers, with distinct distribution patterns and major hair-cycle-associated changes. In the epidermis and around the distal hair follicle and the arrector pili muscle, only calcitonin-gene-related peptide immunoreactive nerve fibers were visualized, whereas substance P and peptide histidine methionine immunoreactive nerve fibers were largely restricted to the dermis and subcutis. Compared to telogen skin, the number of calcitonin-gene-related peptide, substance P, and peptide histidine methionine immunoreactive single nerve fibers increased significantly (p < 0.01) during anagen, including around the bulge region (the seat of epithelial stem cells). Substance P significantly accelerated anagen progression in murine skin organ culture, whereas calcitonin-gene-related peptide and a substance-P-inhibitory peptide inhibited anagen (p < 0.05). The inhibitory effect of calcitonin-gene-related peptide could be antagonized by coadministrating substance P. In contrast to substance P, calcitonin-gene-related peptide failed to induce anagen when released from subcutaneous implants. This might reflect a differential functional assignment of the neuropeptides calcitonin-gene-related peptide and substance P in hair growth control, and invites the use of neuropeptide receptor agonists and antagonists as novel pharmacologic tools for therapeutic hair growth manipulation.     

Immunohistochemical localization of interleukin-6-like immunoreactivity to peripheral nerve-like structures in normal and inflamed human skin

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patchtest reactions to nickel sulphate, and in skin specimens from patients with atopic dermatitis and prurigo nodularis. However, IL-6-like immunoreactivity was also found in nerve-like fibres in specimens from nonlesional skin. In skin from patients with positive epicutaneous patch-test reactions there was a statistically significantly (P<0.01) higher number of IL-6-positive nerve fibres in the epidermis than in normal skin, in contrast to the papillary dermis, in which no difference was found. Moreover, there were clusters of nerve-like fibres with IL-6-like immunoreactivity in the dermis of prurigo nodularis lesions. In these nerve-like fibres, the colocalization of the immunoreactivities for IL-6 and calcitonin gene-related peptide was indicated. Localization of immunoreactivity to nerve-like structures surrounding the eccrine sweat glands indicates that IL-6 is present in autonomic as well as in sensory nerve fibres.     

Dermal sheet preparations in the evaluation of dermal innervation in Parkinson's disease and multiple system atrophy

Background:  Evaluation of dermal nerve fibers in conventional vertical sections is difficult because of the small number of fibers available for examination. In this study, we evaluated dermal sheet mounts for fibers in which the majority of fibers can be visualized.
Methods:  We compared the dermal small fiber density in six Parkinson's disease (PD) and six multiple system atrophy (MSA) patients using dermal sheet preparations (DSP). DSP are based on epidermal-dermal separations and immunostaining of the entire dermis by the nerve growth factor receptor p75 antibody that stains both autonomic and sensory fibers.
Results:  The small fiber density was reduced in PD compared with MSA (p < 0.0001), suggesting the presence of small fiber neuropathy in PD.
Conclusions:  DSP offer a unique method of evaluation of dermal nerve fibers. This method can be used to evaluate small nerve fibers in many neurological disorders such as MSA and PD.     

Bird's eye view observations of the subepidermal nerve network of normal guinea pig skin

This study was undertaken to visualize the subepidermal nerve networks immunohistochemically. Specimens were obtained from the normal skin of the back, abdomen and nose of seven adult male Hartley guinea pigs, and immersed in 1 M NaCl solution. Dermal sheets were obtained by separating the dermis and epidermis, followed by fixation in Zamboni's fixative. The dermal sheets were sectioned parallel to the separated surface. Using the immunoperoxidase technique and immunofluorescence, the sections were immunostained with primary antibodies to S 100 protein (S100), protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP). In double-labeled immunofluorescence of PGP 9.5 and SP or CGRP, the sections were viewed under a confocal laser scanning microscope. In skin of the back and abdomen, networks of S100-, PGP 9.5- and NSE-positive fibers were observed, some of which showed a multicentric arrangement. The outermost structures were formed by the thickest fibers which were 5-10 micro m thick, the outer networks consisted of fibers 3-6 micro m thick, and the inner networks consisted of fibers 1-3 micro m thick. From these networks, single fibers approximately 0.5 micro m thick branched out and terminated in free endings. The SP- and the CGRP-positive substances appeared as granules on the PGP 9.5-positive fibers. These results confirm that the dermis has a three-layered sensory nerve plexus, i.e. deep, superficial and subepidermal. In the skin of the nose, however, nerve networks were made up of only thick fibers which were probably situated in the subpapillary dermis.     

Increased nerve growth factor and its receptors in atopic dermatitis: an immunohistochemical study

Evidence suggests that neurotrophins may regulate certain immune functions and inflammation. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored using immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in early lesions of atopic dermatitis (AD). In AD involved skin, strong NGF-immunoreactive (IR) cells were observed in the epidermis. In some cases, a huge number of infiltrating cells with stronger NGF immunoreactivity was seen mainly in the dermal papillae. Some trkA immunoreactivity was observed in the outer membrane of cells in the basal and spinal layers of the epidermis. In the papillary dermis, a larger number of cells demonstrated strong trkA immunoreactivity. The p75 NGFr-IR nerve fibre profiles were increased (900 per mm²; p<0.001) compared to normal [the involved skin also differed from the uninvolved skin (p<0.05)] in the dermal papillae. These nerve fibres were larger, coarser and branched, some of them terminated at p75 NGFr-IR basal cells, and also revealed a stronger fluorescence staining than the controls or the uninvolved skin. In normal healthy volunteers and AD uninvolved skin, the NGF immunoreactivity was weak in the basal layer of epidermis. Only a few trkA positive cells were seen in the basal layer of the epidermis and upper dermis. The IR epidermal basal cells revealed a striking patchy arrangement with strong p75 NGFr immunostaining in the peripheral part of the cells, and short and thick NGFr-IR nerve fibre profiles appeared as smooth endings scattered in the dermis including the cutaneous accessory organs. Using NGF and p75 NGFr double staining, both immunoreactivities showed a weak staining in the epidermis and dermis in normal and uninvolved skin. In the involved dermis of AD, the intensity of p75 NGFr-IR nerves was stronger in areas where there were also increased numbers of NGF-IR cells. These findings indicate that NGF and its receptors may contribute to the neurohyperplasia of AD.     

Quantification of cutaneous sensory nerves and their substance P content in psoriasis

The aim of the present study was to extend our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic, and that substance P mediates the inflammation. For this purpose, the pattern of neurofilament-positive sensory nerve fibers was studied and the lengths and substance P content of these fibers measured morphometrically in dermal and epidermal compartments of the psoriatic lesion, psoriatic but lesion-free skin, and control skin. The epidermis and dermis of the psoriatic lesions were significantly more densely innervated with neurofilament-positive fibers than either lesion-free psoriatic or control skin. Although substance P is known to be rapidly degraded in tissues, and its actual concentrations in the sections were unknown, there was an increase in substance P containing nerves in the psoriatic lesion, the increase being significant in the epidermal nerve fibers. No significant differences in the measured parameters were obtained between lesion-free psoriatic and control skin. These results indicate that there is an altered pattern of sensory nerves in a psoriatic plaque and that substance P may be an important mediator in the inflammatory processes that contribute either to the initiation or maintenance of a psoriatic lesion.     

Vasoactive intestinal polypeptide in allergic contact dermatitis: an immunohistochemical and radioimmunoassay study

Abstract Vasoactive intestinal polypeptide (VIP) is a neuropeptide with immunomodulatory properties. To elucidate the possible role of VIP in the pathophysiology of cutaneous contact hypersensitivity, we compared involved with uninvolved skin of allergic contact dermatitis (ACD) from nickel-allergic patients. Assays included quantification of VIP-immunoreactive (VIP-IR) nerve fibres and cells bearing immunoreactivity for VIP1 and VIP2 receptors in skin biopsy specimens, and of the concentration of VIP-like immunoreactivity (VIP-LI) in extracts of biopsy specimens. VIP-IR nerve fibres were found in the deeper part of the dermis close to sweat glands and hair follicles. No difference in the presence of VIP-IR nerve fibres was found between involved and uninvolved skin of ACD. VIP1 and VIP2 receptor immunoreactivity was seen on keratinocytes in the basal layer of the epidermis, with no difference between involved and uninvolved skin. Staining was also seen on vessel walls and mononuclear cells in the dermis. The highest staining intensity in the mononuclear cells was noted with the antibodies against the VIP2 receptor. While most of the mononuclear cells were stained in uninvolved skin, a minority of the cells showed a positive signal in involved skin. The concentration of VIP-LI in uninvolved skin was 1.53 ± 0.790 pmol/g and in involved skin 1.41 ± 0.735 pmol/g. It is concluded that there is no significant difference in either the distribution of VIP-IR fibres or the concentration of VIP-LI between involved and uninvolved skin of ACD. However, the number of dermal mononuclear cells showing VIP2 receptor immunoreactivity in skin of ACD was reduced. Received: 4 May 1998 / Received after revision: 12 October 1998 / Accepted: 16 October 1998     

Immunohistochemical studies on NAP-1/IL-8 in contact eczema and atopic dermatitis

Summary The neutrophil activating peptide NAP-1/IL-8 has in the past been shown to be secreted by diverse cell-types involved in inflammatory processes. Furthermore, potent biological effects on both neutrophilic granulocytes and lymphocytes enforce its role in inflammation. Recently, immunohistochemical studies using monoclonal anti-NAP-1/IL-8 antibodies have been performed on dermal inflammatory conditions like psoriasis vulgaris. These have demonstrated epidermal IL-8 immunoreactivity in a pattern inversely related to the degree of inflammatory infiltration. Based on these results, in the present study biopsies from patients with contact eczema as well as atopic dermatitis were examined. The same patterns of immunoreactivity were found with either homogenous epidermal staining, focally negative staining or overall decreased or even absent staining. As in psoriasis, these patterns were related to the degree of inflammatory infiltration. These results prove NAP-1/IL-8 to be involved not only in psoriasis vulgaris, but more likely to be a marker of different inflammatory processes. Future work will have to examine the kinetics as well as stimuli causing these effect.     

Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres

The purpose of this study was to gain an understanding of why phototherapy relieves itching. Skin samples (3 mm punch biopsies) from non-inflamed gluteal skin of 10 patients undergoing phototherapy were compared before and after 20 treatments. All the cutaneous nerve fibres here visualized by antibodies against PGP 9.5, sensory nerve fibres by antibodies against calcitonin gene-related peptide (CGRP) and capsaicin-sensitive primary nociceptive afferents by antibodies against VR1-receptor. Following treatment, the number of PGP 9.5-positive nerve fibres in the epidermis was reduced from 193 +/- 52 to 102 +/- 34 (p < 0.0001) and the number of CGRP-immunoreactive nerve fibres, which occurred only in dermis, was reduced from 28 +/- 15 to 22 +/- 7 (p = 0.04). The VR1-immunoreactive nerve fibres, some of them containing immunoreactivity to CGRP, were not affected. The success of phototherapy in combating itch may at least partly be linked with the reduction in the number of epidermal nerve fibres. The reduction in the number of CGRP-immunoreactive nerve fibres in the dermis may contribute to the beneficial effects of UV irradiation on the inflammatory process.     

The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.     

多发性毛盘瘤国内首例报告

目的 报告1例多发性毛盘瘤。患者男,31岁。主诉右下肢出现多发性高梁米粒至小豆大小坚实性皮色丘疹15年,左膝关节、左小腿部同样皮损近1年,无自觉症状。方法和结果 组织病理显示表皮棘层肥厚,真皮上部为细网状胶原纤维增殖和局灶性黏蛋白沉积,细小血管和神经纤维成分增多,弹力纤维增殖限局于毛囊和表皮突周围。增生毛囊见于病变两侧边缘,呈衣领状向下延伸。超微结构示Merkel细胞-轴突复合体位于表皮下基底板上方,真皮上部见有髓神经纤维。血管超微结构有的基底板显示层状结构,时见血管壁纤维成分增殖,管壁增厚。结论 本病罕见,系来源于毛盘的一种错构瘤。     

The aniline blue fluorescence staining of eosinophilic granulocytes

An aniline blue fluorescence staining technique specific for eosinophils was compared to haematoxylin and eosin to determine the percentages of eosinophils in the peripheral blood of patients with atopic or with allergic contact dermatitis. The aniline blue technique proved to be excellent for demonstrating eosinophilic granulocytes. Although the eosinophilic granulocytes were reasonably demonstrable in thin layers stained with haematoxylin and eosin, the aniline blue staining seems to be better in cases of doubt. Using the same techniques the presence of eosinophil granulocytes was studied in 5 punch biopsies taken from positive patch tests (after 48 h) and 5 biopsies from positive skin reactions after and intradermal injection with an atopic allergen (after 20--30 min). In all punch biopsies taken after an intradermal injection with an atopic allergen, eosinophilic granulocytes, often numerous, were seen in the vessels of the dermis. In punch biopsies taken from positive patch tests the eosinophilic granulocytes were seen scattered through the dermis in variable numbers.     

Immunoreactivity to material like vasoactive intestinal polypeptide in epidermal cells of lichen sclerosus et atrophicus

Immunoreactivity to material like vasoactive intestinal polypeptide was found to occur within certain cellular elements of the epidermis in two patients out of four who had lesions of lichen sclerosus et atrophicus. No specific immunofluorescence to the material could be seen in the dermis, apart from single immunoreactive nerve fibers.     

Can the brain inhibit inflammation generated in the skin? The lesson of α‐melanocyte‐stimulating hormone

The neuro-immuno-cutaneous-endocrine network is not a simple construct featuring organ systems intimately involved in the bridge between body and mind. Mind-body influences are bi-directional and the skin should be considered an active neuroimmunoendocrine interface, where effector molecules of neuropeptides act as common words used in a dynamic dialogue between brain, immune system and skin. Gamma-melanocyte stimulating hormone (gamma-MSH), one of the principal neuroimmunomodulating peptides, seems to exercise some control on the cutaneous inflammatory process, through a central action mediated by descending anti-inflammatory neural pathways and via local direct influence on inflammatory cells infiltrating the dermis, such as monocytes, macrophages and neutrophils. Gamma-MSH down-regulates the production of proinflammatory cytokines, while the production of the anti-inflammatory cytokine IL-10 is stimulated by gamma-MSH. Finally, gamma-MSH seems to regulate the expression of surface molecules in immunocompetent cells. Thus, further studies may lead to the use of gamma-MSH as an important anti-inflammatory agent in clinical dermatology.     

Histological findings after brown recluse spider envenomation

Histologic specimens from 41 rabbits were studied for changes resulting from the manual injection of brown recluse spider venom. Major findings included a mixed inflammatory cell infiltrate, coagulative tissue necrosis, and vasculitis. All specimens demonstrated a well-delineated zone of eosinophilic staining recognizable as "mummified" coagulative necrosis of the epidermis and dermis. A dense band of neutrophils bordered the zone of necrosis. Immediately adjacent to the neutrophilic band, small vessel vasculitis was a universal finding. Degranulated eosinophils and neutrophils and macrophages filled with eosinophilic granules were common. Inflammatory foci were often centered on groups of lipocytes within the dermis. Large vessel vasculitis resembling that seen in polyarteritis nodosa was present deep to 7 of the 40 eschars. Large vessel vasculitis may contribute to the large zones of necrosis seen after some brown recluse spider bites. Eosinophils may play a role in tissue damage after envenomation.     

Histamine-containing mast cells and their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal

The mast cell, which is a histamine-containing cell, has been found to have far more functions in skin inflammation than hitherto understood. To investigate the appearance of mast cells in prurigo nodularis, histamine immunohistochemistry in combination with nerve growth factor receptor (NGFr) double-staining as well as electron microscopic studies were performed. The results revealed that the histamine-containing cell number was increased in the lesional dermis. The mast cell size was also increased and the shape had become more dendritic. They tended to contact the epidermis and even infiltrated into it. In the histamine and NGFr double-staining, both an increased histamine-containing mast cell number and an increased number of NGFr-immuno-reactive nerve fiber profiles were revealed in the upper dermis of the prurigo nodularis lesional skin. Mast cells were seen in close vicinity to NGFr-positive nerves and sometimes even seemingly to contact single nerve fibers. At the ultrastructural level, it is obvious that the mast cell bodies become larger, having more abundant cytoplasm and organelles (e.g. mitochondria), but comparatively fewer characteristic granules. Mast cells were often observed to sprout long dendrites, with or without granules. The cells were also frequently seen to contact other cell types, and a mast cell infiltration into the epidermis was also found. The statistical results of mast cell numbers showed a significant increase in prurigo nodularis lesional skin compared to the normal controls. The present results further indicate that mast cells, together with cutaneous nerve fibers, are actively involved in the pathogenesis of the disease.     

Expression of 36-kDa microfibril-associated glycoprotein (MAGP-36) in human keratinocytes and its localization in skin

Microfibril-associated glycoprotein-36 (MAGP-36) is a recently isolated elastin-binding protein and considered to be a member of microfibril-associated glycoproteins (MAGPs). We studied the expression of MAGP-36 in cultured normal human keratinocytes and its localization in the skin. MAGP-36 was found to be expressed in cultured human keratinocytes by Western blot and RT-PCR assays. The levels of MAGP-36 (polypeptide and mRNA) and the number of MAGP-36-producing keratinocytes were greatly increased during Ca(2+)-induced differentiation of keratinocytes. Immunohistochemical studies demonstrated that MAGP-36 colocalized with elastic fibers and formed candelabra like-fibers in the superficial dermis of normal skin. In the elderly skin of sun-exposed region, immunoreactivity of MAGP-36 in the superficial dermis disappeared. In the lesional skin of pseudoxanthoma elasticum which is an elastin-related disorder, immunoreactivity of MAGP-36 was found in the accumulation of disintegrated elastic fibers. The results show that MAGP-36 is a component of elastic fibers in the dermis and co-operates with elastin in normal and diseased conditions.     

成人斯蒂尔病1例

患者女,69岁。右侧面部红斑、水疱后疼痛14个月,反复发热、关节痛1年,全身散在分布皮疹5月。体检:面部片状暗红斑,上覆暗红色和黄色痂皮,痂皮下可见点状溃疡和脓性分泌物;背部及双侧上肢散在分布10余个约1.0cm×1.5cm大萎缩性斑块,表面有少许痂屑,部分挤压后有少许脓液;右侧肘部可见淡红色斑块,内侧有一直径约0.5cm的厚壁水疱,疱液稠。实验室检查:血白细胞、中性粒细胞均升高,血清铁蛋白增高,类风湿因子、抗核抗体阴性,抗生素治疗无效。皮损组织病理示:真皮浅层及血管壁部分淋巴细胞、中性粒细胞浸润,淋巴结活检呈反应性增生改变。诊断:成人斯蒂尔病。