Histopathologic characteristics of neonatal cutaneous lupus erythematosus: description of five cases and literature review

Background:  Neonatal lupus erythematosus (NLE) is a disease associated with the transplacental transfer of maternal anti-Ro/SSA. The histopathologic characteristics of neonatal lupus have been described as compatible with cutaneous lupus based on isolated cases.
Methods:  We retrospectively review the available literature and compare them with findings obtained in seven biopsies of five cases.
Results:  Erythematous-desquamative lesions and urticaria-like lesions were observed in our series. Two cases showed both type of lesions. Vacuolar alterations at the dermoepidermal interface and adnexal structures were the histopathologic findings on erythematous-desquamative lesions, and a superficial and deep perivascular and periadnexal lymphocytic infiltrate was the major pattern in urticaria-like lesions. One case showed prevalence of eosinophils in the inflammatory infiltrate. Sixty cases have been reported previously. Sixty-five percent presented erythematous-desquamative and 29% urticaria-like lesions. Pathologic findings of erythematous-desquamative lesions were similar to those found in our series, but epidermal vacuolar changes were the predominant histopathologic finding in urticaria-like lesions of cases reported in the literature.
Conclusions:  The majority of cases of NLE show vacuolar alteration at the dermoepidermal interface and adnexal structures. Some cases exhibit a superficial and deep perivascular and periadnexal lymphocytic infiltrate without epidermal alteration, and rare cases may have eosinophils in the infiltrate.     

Severe local skin reactions to interferon beta-1b in multiple sclerosis-improvement by deep subcutaneous injection

Severe local skin reactions to subcutaneous injection of interferon beta-1b in multiple sclerosis are rare, and only 12 cases of severe skin reaction due to interferon beta-1b have been reported to date. We report two cases of severe skin reactions in multiple sclerosis patients following the injection of subcutaneous interferon beta-1b. In case 1, after five years of treatment, a painful indurated erythematous lesion appeared at the injection site on the left buttock. On histological analysis, the lesion showed septal and lobular panniculitis with lymphocytic infiltration. In case 2, cutaneous ulceration was surrounded by painful induration, which developed at the injection site on the right thigh after four years of treatment. The lesions resolved rapidly after discontinuation of interferon beta-1b treatment in both cases. Here, we review cases of similar lesions caused by interferon beta-1b reported in the literature, and discuss the characteristics, mechanism, treatment, and prevention of such lesions.     

Lobular panniculitis at the site of subcutaneous interferon beta injections for the treatment of multiple sclerosis can histologically mimic pancreatic panniculitis. A study of 12 cases

Background:  Thrombosis, mucinosis and necrosis are well-described complications of subcutaneous interferon beta injections.
Methods:  We report 12 incisional biopsies from subcutaneous interferon beta injection sites in 12 multiple sclerosis (MS) patients from a single neurologist's practice.
Results:  We identified abscesses (two cases) or induration (two cases) in acute clinical lesions and lipoatrophy (eight cases) in chronic lesions (biopsied over a year after symptom onset at injection sites). Biopsies from three acute lesions showed vascular thrombosis, dermal mucinosis, lobular neutrophilic panniculitis, necrosis, calcification and hemosiderin deposition (biopsied 2 weeks to 2 months after symptom onset). Two cases contained sterile abscesses. Five of the eight chronic cases presented as hard, indurated lipoatrophy with livedo reticularis. Their biopsies showed subcutaneous calcification and lipoatrophy. Biopsies from the early calcific suppurative and late calcific atrophic phases histologically resembled the early and late phases of subcutaneous saponification in pancreatic panniculitis.
Conclusions:  Reactions at the site of subcutaneous interferon beta injections are common. Lipoatrophy can be clinically identified in 39 of 85 MS patients (46%) receiving subcutaneous interferon beta injections for 1 year or longer in our practice. A reaction to interferon should be considered in the differential diagnosis of biopsies that show features of pancreatic panniculitis.     

Lichenoid and subacute cutaneous lupus erythematosus-like dermatitis associated with antihistamine therapy

The authors report the occurrence of lichenoid and/or subacute lupus erythematosus-like eruptions in a group of patients receiving agents with antihistaminic properties. In 1 of the patients the eruption clinically resembled lichen planus, while in 5 patients the eruption resembled subacute cutaneous lupus erythematosus (SCLE). At a light microscopic level all cases showed a lichenoid dermatitis and in 4 cases the lesions were interpreted as representing subacute lupus-like eruptions by virtue of the presence of alternating cell poor and lichenoid interface dermatitis, suprabasilar lymphocytosis around degenerating keratinocytes, and dermal mucinosis. Despite the resemblance at a clinical and light microscopic level to SCLE, anti-Ro seropositivity could not be established in any of the cases. One case, however, did demonstrate antihistone antibodies in concert with a high antinuclear antibody titer. A causal association was implicated by virtue of lesional resolution following drug withdrawal. The association of cutaneous eruptions resembling SCLE with antihistamine intake is seemingly a novel one. The possible pathogenetic basis of the eruptions is discussed.     

Successful treatment of verruca plantaris with a single sublesional injection of interferon-α2a

Background.  Interferons are molecules with antiviral effects, which have been used for the treatment of verruca for many years.
Aims.  To determine if sublesional interferon (IFN)-α injection offers an effective alternative treatment for common warts.
Methods.  We compared the results of single-dose sublesional IFN application in different types of verruca and with placebo for the treatment of single verruca plantaris lesions. In total, 53 patients (mean age 22.6 years) were enrolled in the study. Of these, 45 patients received a single sublesional injection of 4.5 MU IFN-α2a (three study groups), and eight patients with single verruca plantaris lesions were injected with physiological saline as placebo (control group). As local anaesthesia, liquid nitrogen was sprayed only on to the injection site for 3–4 s. The injection was made directly under the lesion through the border of the lesion, at with approximately a 45° angle from healthy skin.
Results.  At the 12-month follow-up in the group of patients with single verruca plantaris, there were 19 complete cures (7.2%) and 2 partial responses (8.3%), and 3 patients (12.5%) had no response. In the control group, only 2 patients (25%) had a partial response to treatment.
Conclusions.  These results suggest that a single sublesional dose of 4.5 MU IFN-α may be of value in the treatment of patients with verruca, especially in those with single verruca plantaris lesions.     

Discoid lupus erythematosus-like eruption induced by infliximab

Lupus erythematosus-like syndromes have been reported as an adverse effect of anti-tumour necrosis factor-alpha therapy. We report the case of a patient with rheumatoid arthritis who developed a discoid lupus erythematosus-like eruption after treatment with infliximab. The rash consisted of diffuse scaly erythematous plaques on the face, trunk and extremities, and occurred in the context of elevated anti-nuclear and anti-double-stranded DNA antibody titres. Direct immunofluorescence of lesional skin showed linear deposition of IgG, IgM and C3. The lesions resolved completely after the discontinuation of infliximab and with the use of anti-malarial therapy. We discuss the clinical, histological and immunohistochemical features of this case and review the literature with respect to the incidence of lupus erythematosus-like syndromes in patients receiving tumour necrosis factor-alpha antagonists.     

Granulomatous and suppurative dermatitis at interferon alfa injection sites: report of 2 cases

It has previously been reported that interferon alfa injection sites may develop pyoderma gangrenosum, interface dermatitis, vasculitis, or, more commonly, ulcers characterized by intravascular thrombi and a mixed inflammatory cell infiltrate. We describe 2 patients in whom granulomatous and suppurative dermatitis developed at interferon alfa injection sites. These cases extend the spectrum of interferon alfa injection site reactions. The histologic and clinical similarities of these cases with pyoderma gangrenosum and cutaneous Crohn's disease are explored.     

Ticlopidine-induced subacute cutaneous lupus erythematosus: A case report and literature review

Many drugs have been reported to induce lupus in a minority of patients. Ticlopidine hydrochloride inhibits platelet aggregation and is widely used for the prevention of thrombosis. There have been only a few reports of ticlopidine-induced lupus. Here, we review 13 previously reported cases and describe the case of a 71-year-old man with ticlopidine-induced subacute cutaneous lupus erythematosus. His diagnosis was supported by the appearance of papulosquamous skin lesions on sun-exposed areas and detectable anti-Ro/SS-A antibodies, shortly after drug initiation as well as the gradual resolution of these symptoms after the discontinuation of ticlopidine. Our case highlights that when a patient presents with subacute cutaneous lupus erythematosus-like skin lesions, ticlopidine should be considered as a potential causative agent.     

Cutaneous metastasis of inflammatory breast carcinoma mimicking an erythema annulare centrifugum: a sign of locally recurrent cancer

Erythema annulare centrifugum (EAC) is a clinical reaction pattern that includes lupus erythematosus, spongiotic dermatitis (particularly pityriasis rosea), pseudolymphoma and cutaneous B‐cell lymphoma. However, it can be the result of cutaneous metastasis by an internal carcinoma. We present the case of a 38‐year‐old woman with bilateral inflammatory breast cancer following multimodal therapy. After chemotherapy, the patient developed EAC on her back, clinically suspect of subacute cutaneous lupus erythematosus. A skin biopsy of annular lesion revealed dermal lymphatic infiltration by inflammatory breast carcinoma. Immunohistochemically, HER2 overexpression and negativity for hormone receptor are the hallmarks of this disease. Cutaneous metastasis by inflammatory breast carcinoma mimicking EAC is rare, and it has not been described in extramammary locations. Its recognition by the dermatologist is important because it can be a clinical manifestation of locally recurrent cancer.     

Fibro-osseous pseudotumor of the digit: a comparison to myositis ossificans by light microscopy and immunohistochemical methods

Fibro-osseous pseudotumor of the digit is an unusual cutaneous process characterized histologically by a fibroblastic proliferation admixed with reactive/metaplastic osteoid formation. The osteoid formation can be florid and immature, mimicking the appearance of malignant osteoid-forming neoplasms. Fibro-osseous pseudotumor of the digit has histologic and clinical features in common with myositis ossificans. This has led many to consider the two to be synonymous. We studied three cases of fibro-osseous pseudotumor, compared to five cases of myositis ossificans, using routine light microscopy and a battery of immunohistochemical stains.
Both entities displayed a "zoning" pattern of immature spindled areas admixed with more mature areas having osteoid metaplasia. This was more pronounced in myositis ossificans. In each lesion, the spindle cells stained positively for vimentin and actin. CD34 and Factor VIII highlighted the vasculature. No stromal staining for MAK-6 (cytokeratin) or S-100 was identified. Ki-67, a proliferation marker, showed positive staining of the stromal cells in both lesions, which was strongest in the immature spindled areas. The immunohistochemical and histologic similarities of the lesions support fibro-osseous pseudotumor of the digit being a cutaneous variant of myositis ossificans.     

Necrotizing cutaneous lesions complicating treatment with pegylated-interferon alfa in an HIV-infected patient.

Pegylated interferon alfa is a pegylated formulation of recombinant human interferon (IFN) conjugated with polyethylene-glycol (PEG). The major advantages of this formulation, compared to standard IFN, is a prolonged half-life which allows for once-weekly injection. Its antiviral efficacy in association with ribavirin as a new standard treatment of chronic hepatitis C has been recently documented. Efficacy of PEG-IFN in the therapy of HIV infection is currently being evaluated in prospective pilot studies. We describe herein the first observation of cutaneous necrosis at the sites of PEG-IFN injection in an HIV-infected patient. A 50-year-old man, HIV infected, was treated with antiretroviral bitherapy combining zidovudine and didanosine for 30 months. Weekly subcutaneous injections of PEG-IFN-alpha-2b were started at a dose of 1.5 microg/kg. Nine months later, two successive necrotizing cutaneous lesions developed at the site of injection. The cutaneous ulcerations slowly healed under local therapy without interruption or dose modification of the PEG-IFN. We review the literature on previously reported cases of cutaneous necrosis following standard or pegylated IFN-alpha injection and discuss the different pathophysiological mechanisms that might be involved.     

Standard and new treatments in cutaneous B-cell lymphomas

Background:  Primary cutaneous B-cell lymphomas (PCBCL) are cutaneous non-Hodgkin lymphomas and can be classified clinically and by prognosis. The aim of this paper is to perform a review of standard and new treatments.
Method:  This paper provides a literature review of the different treatments of PCBCL.
Results:  Surgery and radiotherapy remain the standard therapies in isolated cutaneous lesions. Systemic or intralesional interferon (IFN)-α may be an alternative in PCBCL with diffuse cutaneous lesions. In aggressive forms with poor prognosis, polychemotherapy is the first line of treatment although rituximab and radioimmunotherapy are evolving therapeutic options.
Conclusion:  In the majority of cases, the treatment of CBCL is straightforward. In aggressive forms, new therapies and biologic therapies may be of real interest.     

Lichenoid keratosis: a clinicopathologic study of 17 patients

BACKGROUND: Lichenoid keratosis (LK) is a rather frequent skin lesion that has some histologic features similar to lichen planus (LP). The clinical and histopathologic characteristics of LK and differential tools from LP are not yet fully established. OBJECTIVE: The purpose of this study was to investigate the clinical and histopathologic characteristics of LK. METHODS: A clinical survey was done with 17 patients diagnosed as having LK. We reevaluated biopsy materials of 17 patients diagnosed during the past 10 years at Asan Medical Center, Seoul, Korea. We performed an immunohistochemical staining in 17 cases of LK and 7 cases of LP using 5 antibodies for CD3, CD4, CD8, CD20, and cutaneous lymphocyte-associated antigen (CLA). Standard streptavidin-biotin peroxidase method using the monoclonal antibodies with 3-amino-9-ethyl-carbazole was used. RESULTS: The male/female ratio was 1:1.1. The mean age at diagnosis was 54.9 years. The face was the most commonly affected site, followed by the arm and forearm, dorsum of hand, chest, trunk, abdomen, and leg. The lesions were predominantly solitary (76.5%); 1 patient had 4 lesions; 3 patients (17.6%) had numerous lesions. The lesions ranged in size from 0.4 to 2.0 cm. Histopathologically, all the cases showed characteristic lichenoid infiltrates of lymphocytes, occasional parakeratosis, and apoptotic bodies in the epidermis without nuclear atypia of keratinocytes. LK could be reclassified into 3 patterns by means of histopathologic findings: LP-like (11/17), seborrheic keratosis-like (3/17), and lupus erythematosus-like (3/17). Immunohistochemical studies revealed that infiltrated epidermal and dermal lymphocytes in LK consisted mainly of CD8(+) T cells and partly CD20(+) B cells. In LP, epidermal lymphocytes were mainly CD8(+) T cells and dermal lymphocytes were CD4(+) or CD8(+) T cells. Interestingly, CLA was strongly expressed in LP but not expressed in LK. CONCLUSION: We reclassified LK as follows: LP-like LK, seborrheic keratosis-like LK, and lupus erythematosus-like LK. Immunohistochemical stains for CLA as well as CD4 and CD8 may be valuable tools in the differential diagnosis between LK and LP.     

Annular erythema associated with Sj?gren's syndrome: a variant of systemic lupus erythematosus

We present a Burmese patient with widespread annular erythema associated with Sj?gren's syndrome. Unlike previously described cases, the disease occurred in the setting of systemic lupus erythematosus. Photoprovocation testing revealed light sensitivity in the UVA range with elicitation of subacute cutaneous lupus erythematosus-like lesions. The presence of an erythema annulare centrifugum-like eruption should initiate the search for Sj?gren's syndrome and systemic lupus erythematosus.     

Histopathology of cutaneous lupus erythematosus

The basic histopathologic feature of all cutaneous lesions of lupus erythematosus involves a perivascular mononuclear cell infiltrate with subsequent involvement of the epidermis and appendages. The various histologic alterations affecting the epidermis, dermis, and adnexal structures reflect the particular type of lesion biopsied and the duration of the lesion at the time of biopsy. The different clinical and serologic forms of lupus erythematosus cannot reliably be distinguished histologically, which supports the premise that lupus erythematosus is a disease with a wide spectrum of clinical manifestations but with a common underlying pathogenesis.     

Diagnostic value of CD163 in cutaneous spindle cell lesions

Background:  The histologic diagnosis of atypical fibroxanthoma (AFX) can sometimes be challenging. No specific marker exists to confirm the diagnosis other than excluding other entities. CD163 has been shown to have great specificity for tumors of monocyte/histiocyte lineage. In this study, we evaluated the diagnostic utility of CD163 in diagnosing AFX and in identifying skin lesions with histiocytic/dendritic derivation.
Methods:  A total of 157 cases, including 14 AFXs, 5 spindle cell squamous cell carcinomas (SCCs), and 7 spindle cell/desmoplastic melanomas, along with other cutaneous spindle cell and histiocytic/fibrohistiocytic lesions, were stained with CD163.
Results:  CD163 was expressed in 11 of 14 (79%) AFXs, with moderate to strong intensity. No staining was observed in cases of spindle cell SCC (0/5) and dermatofibrosarcoma protuberans (0/10). Rare spindle cell/desmoplastic melanomas (2/7) and cutaneous leiomyosarcomas (1/5) demonstrated positive staining. CD163 reactivity was seen in 24 of 29 of benign fibrous histiocytomas (BFHs), including 8 of 8 celular fibrous histiocytomas and 6 of 9 epithelioid cell histiocytomas. The majority of cutaneous histiocytic lesions, including juvenile xanthogranuloma, Langerhans cell histiocytosis and Rosai–Dorfman disease, were positive for CD163.
Conclusion:  CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions.     

Subacute cutaneous lupus erythematosus: Clinicopathologic findings in thirteen cases

The clinicopathologic and serologic findings of thirteen patients with subacute cutaneous lupus erythematosus are reported. The clinical and immunologic features are similar to those described by most other authors. From a histologic point of view, however, two aspects could be emphasized: the presence of a larger number of epidermal colloid bodies and severe epidermal necrosis (more than 60% of cases). All patients with this microscopic picture have a similar clinical and serologic pattern: annular lesions, anti-Ro antibodies and human leukocyte antigen-DR3.     

Phenol application to angiosarcomas: implications and histologic studies

Background  Cutaneous angiosarcoma (AS) is an aggressive endothelial sarcoma that arises in elderly people. Effective treatment options are limited. Phenol application has been reported to be effective and economical.
Aims  To evaluate the efficacy of phenol application for the treatment of AS, and to examine the histologic changes in three cases of cutaneous AS with phenol application.
Methods  After phenol application, biopsy specimens were collected from three patients with cutaneous AS. Paraffin-embedded sections of the skin specimens were then stained with hematoxylin and eosin. The detection of apoptosis was performed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) method, and the depth of TUNEL-positive cell staining was examined.
Results  Phenol treatment induced a strong degeneration of tumor cells and endothelial cells in the dermis, when compared with nontreated areas. Positive staining of tumor cells and/or endothelial cells by the TUNEL method was found in phenol-treated lesions, but not in nontreated lesions. The injurious effects on these tumor cells persisted for as long as 6 h after phenol application.
Conclusion  From a comparison of noninvasive therapy with standard surgical therapy, it is obvious that phenol peeling has several advantages with regard to the ease of the procedure, time efficiency, no need for special equipment, low therapeutic costs, good pain control, and post-treatment follow-up. This study suggests that phenol application can be a supportive treatment for AS.     

Cutaneous involvement by angioimmunoblastic T-cell lymphoma: a unique histologic presentation, mimicking an infectious etiology

Abstract:  Angioimmunoblastic T-cell lymphoma (AILT) is an aggressive peripheral T-cell lymphoma that is frequently accompanied by a cutaneous eruption. The cutaneous findings most commonly consist of a maculopapular eruption on the trunk. However, purpura, infiltrated or urticarial plaques, papulovesicular lesions, nodules, and erythroderma have also been reported. Histologic findings in the lymph node are characteristic, while those in the skin may show one of four patterns. Here, we review the previously reported histologic patterns and present a case of AILT involving the skin with a unique histologic appearance of necrotizing granulomas with abundant histiocytes and eosinophils, mimicking an infectious etiology.     

Cutaneous sarcoidosis: differential diagnosis

Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the "great imitators," making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic studies. Specific lesions include maculopapules, plaques, nodules, lupus pernio, scar infiltration, alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal, and childhood sarcoidosis represent a distinct subset of the disease process. The most common nonspecific lesion is erythema nodosum. Others include calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome. The importance of considering cutaneous sarcoidosis in the clinical differential diagnosis of a given skin lesion relies on the association with systemic involvement and the convenience of the skin as a tissue source for histologic analysis.