Histologic Observations of Coccoid Forms Suggestive of Cell Wall Deficient Bacteria in Cutaneous and Systemic Lupus Erythematosus

The cutaneous lesions of seven consecutive patients with cutaneous lupus erythematosus (LE), two patients with systemic LE, and a patient with both dermatomyositis and cutaneous LE, were studied bacteriologically and microscopically for the presence of bacteria. The study was prompted by the previous reports of variably acid-fast and non-acid-fast bacteria in other collagen diseases, and also by recent reports confirming the presence of cell wall deficient (CWD) bacteria (staphylococci, streptococci, and corynebacteria) within the hematologic elements of both "normal" and diseased individuals. Staphylococcus epidermis was isolated from four cases. Propionibacterium acnes from two cases, and Corynebacterium sp. from one case. Three cases were bacteriologically negative. Basophilic- and eosinophilic-stained coccoid forms, suggestive of CWD bacteria, were identified in the microscopic sections of all the cases, as were non-acid-fast coccoid forms. Definite acid-fast coccoid forms were observed in vivo in two cases of cutaneous LE. The complex bacteriology of LE is discussed, as well as the possibility that variably acid-fast CWD microbes might be the long sought-after etiologic agent or agents in the production of LE.     

Variably acid-fast bacteria in a necropsied case of systemic lupus erythematosus with acute myocardial infarction

A 41-year-old woman with chronic systemic lupus erythematosus (SLE), uncomplicated by sepsis or other "secondary infection," died of an acute myocardial infarction. All of the available necroscopic material was reviewed to determine whether acid-fast cell wall deficient bacteria (CWDB) could be demonstrated in vivo. Variably acid-fast coccoid forms, suggestive of CWDB, were observed in specially-stained (intensified Kinyoun acid-fast stain) microscopic sections of the heart, lungs, kidney, adrenal glands, brain, connective tissue, and other organs. Acid-fast "hematoxylin bodies" were also observed. The finding of variably acid-fast bacteria in postmortem tissue in SLE may relate to the current finding of variably acid-fast CWDB within the blood stream of "normal" and diseased persons. In addition, the finding of acid-fast bacteria may relate to the previous reports of similar bacteria in scleroderma, pseudoscleroderma, and cutaneous lesions of SLE. The further search for CWDB in necropsied cases of SLE may elucidate the possible pathogenic role, if any, of these microbes in SLE.     

Cutaneous Sarcoid Reactions during Long Term Remission in a Patient with Acute Myelogenous Leukemia

A 68-year-old Japanese man with acute myelogenous leukemia, in long-term remission, developed cutaneous sarcoid reactions on his trunk and extremities. This may suggest that sarcoid-like granulomas be considered as a nonspecific cutaneous sign of underlying leukemia.     

淋巴瘤伴发皮肤肉芽肿的现象及其意义

淋巴瘤可伴发皮肤肉芽肿,其模式主要有两种:一种是淋巴瘤的特异性皮损中出现肉芽肿反应,例如肉芽肿性蕈样肉芽肿和肉芽肿性皮肤松弛症;另一种是淋巴瘤出现非特异的肉芽肿性皮损,主要见于一些系统性淋巴瘤.其组织病理学类型可为结节病样、环状肉芽肿样、结核样等.其机制及其与预后的关系尚不明确.肉芽肿形成可能是造成某些淋巴瘤特殊临床表现的原因,也容易掩盖淋巴瘤的真实面目,在临床和组织学诊断上需谨慎.     

Pleomorphic, variably acid-fast bacteria in an adult patient with disabling pansclerotic morphea

Disabling pansclerotic morphea (DPM) is a rare variant of scleroderma, characterized by immunologic abnormalities and peripheral blood eosinophilia. Sclerodermatous skin specimens from a 24-year-old woman with DPM were studied for the presence of acid-fast bacteria in bacteriologic culture and in microscopic sections. On three of four occasions, a highly pleomorphic organism was cultured from the skin lesions. Detailed bacteriologic investigations indicated that the microbe had unstable and vacillating morphologic characteristics and peculiar acid-fast properties. The organism could be identified as Staphylococcus epidermidis, but it also had stages of growth with morphologic forms more characteristic of a Corynebacterium-like or actinomycetelike microbe. Variably acid-fast coccoid forms, and variably eosinophilic- and basophilic-staining coccoid forms were observed in vivo. The morphologic forms observed in vivo were similar in appearance to some of the growth forms of the microbe observed in vitro, suggesting that such an organism might be implicated to the pathogenesis of DPM.     

Interstitial granulomatous lesions as part of the spectrum of presenting cutaneous signs in pediatric sarcoidosis

Abstract:  Skin findings in childhood sarcoidosis vary greatly, but only a few occurrences have been published in which the histopathology has been characterized well. We describe a child with sarcoidosis in whom the cutaneous findings were atypical, resembling granuloma annulare. Histologic examination of these cutaneous lesions, however, revealed areas of sarcoid-like epithelioid cell granulomas, a palisading granulomatous process with features of granuloma annulare, as well as palisading neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis. This underscores the variability of skin findings in childhood sarcoidosis—even within the same patient—and suggests that sarcoidosis should be considered in the differential diagnosis of children initially diagnosed with granulomatous skin lesions, such as granuloma annulare, palisading neutrophilic, and granulomatous dermatitis or interstitial granulomatous dermatitis, who demonstrate associated signs of systemic disease.     

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 sarcoid-like granulomas in primary immunodeficiency disorders

Summary We report the occurrence of cutaneous sarcoid-like granulomas in one patient with common variable immunodeficiency and another with 'thymoma and hypogammaglobulinaemia". To our knowledge, this is the first time that such skin lesions have been described in patients with primary immunodeficiency. These granulomas may be attributed to a combination of interleukin-2 deficiency and a profound CD4 lymphopenia. The lesions are similar to the non-infectious 'papular eruption' associated with human immunodeficiency virus infection, and might reflect a common pathogenic mechanism.     

Granulomatous vasculitides and the skin

Wegener's granulomatosis, lymphomatoid granulomatosis, and Churg-Strauss granulomatosis may all have cutaneous involvement. The morphology of cutaneous lesions in these disorders varies from macular erythema to frank gangrenous ulceration. Most often lesions are located on the extremities; however, truncal or facial involvement has been reported, the latter especially in Wegener's granulomatosis. A common histologic finding in these cutaneous lesions is necrotizing vasculitis. However, it is also possible to see Churg-Strauss extravascular granulomas and even periarteritis. Cutaneous involvement with these three forms of systemic granulomatosis generally parallels the systemic course. The treatment for the cutaneous lesions is dictated by the treatment for the systemic vasculitis. It is important to recognize that the cutaneous extravascular granuloma and cutaneous granulomatous vasculitis can be associated with other disorders in addition to systemic granulomatosis. These disorders include most importantly lymphoproliferative diseases, inflammatory disorders such as arthritis, autoimmune diseases, and other inflammatory disorders such as sarcoidosis. Cutaneous involvement with giant cell or temporal arteritis is not common, but ulcerative temporal-parietal scalp lesions are distinctive. Although not common in the United States, Takayasu's arteritis may have several cutaneous manifestations, including erythema nodosum-like lesions. Granulomatous vasculitides have a myriad of cutaneous manifestations. Knowledge of these manifestations may allow for prompt diagnosis in many cases and increased surveillance in other cases for associated systemic illnesses.     

Hypodermitis sclerodermiformis and unusual acid-fast bacteria.

We described two patients with localized, chronic, painful, scleroderma-like lesions of the lower part of the leg associated with venous stasis. This type of lesion has been termed "hypodermitis sclerodermiformis," and we review the literature pertinent to this entity. In addition, skin biopsy material was studied for the presence of acid-fast microbes. In both cases, Fite-Faraco-stained tissue sections contained many acid-fast coccoid and giant microbial forms suggestive of transitional L forms. Culture of the lesion in both cases was positive for Staphylococcus epidermidis. Until the cause is fully clarified, the search for acid-fast bacteria appears warranted in formed of pseudoscleroderma such as hypodermitis sclerodermiformis.     

Sarcoidosis Versus Foreign-Body Granulomas

A 42-year-old man developed a papulonodular exanthema 10 years following an injury from a shell explosion. The differential diagnosis between sarcoid-like, foreign-body granulomas and Boeck's sarcoid was inconclusive by histology, but x-ray spectroanalytic examination revealed silicon particles within the epitheloid cell granulomas.     

Diagnosis of sarcoidosis

There is no single specific test available for the clinician to diagnose sarcoidosis with certainty. Alternatively, the diagnosis, in the majority of cases, is not problematic and depends upon identifying typical pathologic features in combination with a compatible clinical presentation. A histologic diagnosis alone is unsatisfactory since the noncaseating granulomas of sarcoidosis are identical to those found in other disease states including berylliosis, hypersensitivity pneumonitis, the noncaseating granulomas of tuberculosis and the fungal diseases, in lymph nodes adjacent to some malignancies, and in lymph nodes draining inflammatory sites (such as in Crohn's disease). Even in the more obvious cases of sarcoidosis, it is important to examine tissue for acid-fast and fungal organisms. Primary tuberculosis, coccidiodomycosis, or histoplasmosis may occasionally mimic sarcoidosis presenting with bilateral hilar adenopathy, pulmonary infiltrates, and erythema nodosum.     

A Pediatric Case of Atypical Mycobacterium avium Infection of the Skin

We report a case of cutaneous atypical mycobacteriosis in a 12-year-old healthy girl due to Mycobacterium avium. The cutaneous symptoms were three well-defined subcutaneous nodules on both buttocks and on the posterior surface of the left thigh. One had a fistulous opening on the skin surface. Histopathological examination revealed epithelioid cell granulomas surrounded by dense lymphocytic infiltration and acid-fast bacteria were seen with modified periodic acid-carbol fuchsin staining. Using Ogawa's medium at 37°C, acid-fast bacteria were isolated from the biopsied specimen and identified by the DNA-DNA hybridization method as Mycobacterium avium. In drug susceptibility test, these were resistant to all antituberculous drugs. Oral administration of minocycline 100 mg/day for two months had little effect on the two remaining lesions, which were therefore excised. Based upon reported cases of Mycobacterium avium complex, we considered that our pediatric patient with multiple intradermal or subcutaneous nodules on the buttocks and the thigh exhibited the characteristic symptoms of M. avium infection.     

Pityriasis lichenoides in a girl with the granulomatous form of common variable immunodeficiency

Pityriasis lichenoides (PL) is a cutaneous disease of unknown origin. In our 8-year-old female patient with the granulomatous form of common variable immunodeficiency (CVID), PL occurred together with massive splenomegaly and intra-abdominal lymphadenopathy. Prednisone was efficient for treatment of her splenomegaly and autoimmune cytopenias. However, PL was resistant to both topical and systemic steroid treatment. Healing of PL was achieved with the use of a super-potent topical steroid, clobetasol propionate. A defect of T-cell function in CVID may contribute to development of PL. In the granulomatous form of CVID, sarcoid-like granulomas are the most commonly reported cutaneous lesions. PL has not been previously reported.     

Cutaneous silica granuloma. A rare entity or rarely diagnosed? Report of two cases with review of the literature.

Cutaneous silica granuloma is a poorly understood, uncommon condition that may mimic cutaneous sarcoidosis. We describe two cases of this entity and their characteristic latency period (between the time of silica exposure to the time of clinical onset of granuloma). We also review the histologic and energy dispersive x-ray analysis data, which prove the diagnosis. This condition should be recognized as an occupational dermatosis as well as the result of past incidental cuts or abrasions, which result in the development of granulomas, many in old wound scars. Differentiation from cutaneous sarcoidosis is possible with polarized light microscopy and energy-dispersive x-ray analysis.     

Sarcoidosis subcutánea

—Subcutaneous sarcoidosis is characterized by mobile, painless, limb nodules composed of sarcoidal granulomas within fatty tissue, without epidermal involvement. Although cutaneous involvement is found in about a quarter of patients with sarcoidosis, subcutaneous nodules, which may occur in association with other cutaneous lesions, are rare. Less than 40 cases of subcutaneous sarcoidosis have been published the literature.We here report the case of a 63 year-old woman who presented deep, nodular and subcutaneous plaques in extremities for the last 15 days. Histopathology of the cutaneous lesions revealed noncaseating granulomas in subcutaneous tissue, consistent with subcutaneous sarcoidosis. Special stains failed to show foreign material, fungi or acid-fast organism. Thoracic lymphadenopathia were noted in a chest X-ray. Treatment with steroids during 2 months induced an excellent response.     

Persistent unilateral orbital and eyelid oedema as a manifestation of Melkersson–Rosenthal syndrome

Melkersson-Rosenthal syndrome (MRS) is a complex neuromucocutaneous disorder characterized by localized orofacial oedema and cranial nerve dysfunction, frequently associated with minor signs, including furrowed tongue. Complete forms are rare whereas mono- and oligosymptomatic variants are more common. A 71-year-old man presented with a 2-year history of relapsing and progressively persistent oedema of the right eyelids and periorbital region. A fissured tongue and telangiectatic rosacea had been present since the age of 50 and 60 years, respectively. The patient was also affected by essential hypertension and diabetes mellitus. A skin biopsy showed a marked upper dermal oedema, and small epithelioid cell granulomas arranged in perivascular and perilymphatic location. Collections of small epithelioid cells were occasionally observed within lymphatic spaces. No acid-fast bacteria, fungi or foreign bodies were detected. Intralesional corticosteroids induced transient improvement, whereas minocycline, clofazimine and dapsone have been ineffective. MRS may present with unilateral eyelid and periorbital swelling. Differential diagnoses of such cases may include a variety of cutaneous, ophthalmic and systemic diseases.     

Cutaneous infections due to nontuberculous mycobacteria: histopathological review of 28 cases. Comparative study between lesions observed in immunosuppressed patients and normal hosts

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty-eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and 1 Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. In immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from three patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid-like granulomas, a diffuse infiltrate of histiocytic foamy cells, acute and chronic panniculitis, non-specific chronic inflammation, cutaneous abscesses, suppurative granulomas and necrotizing folliculitis can be detected. Suppurative granulomas are the most characteristic feature in skin biopsy specimens from cutaneous NTM infections. Some histopathological patterns seem more prevalent in immunosuppressed patients.     

Immunohistochemical features of cutaneous granulomas in primary immunodeficiency disorders: a comparison with cutaneous sarcoidosis

Background:  Cutaneous granulomas can occur in patients with a primary immunodeficiency disorder. In some cases, an infectious cause cannot be revealed. The pathogenesis of these granulomas still remains to be elucidated. The aim of this study was to study differences or overlap between these rare granulomas and sarcoidosis-related granulomas.
Methods:  Markers for T-cell subsets (CD3, CD4, CD8 and CD45RO), Langerhans' cells (CD1a), macrophages (CD68), B cells (CD20) and NK cells (CD56) were stained immunohistochemically. The amount of CD4+ and CD8+ cells in the granulomas was counted. Results were compared with the CD4+/CD8+ ratio in peripheral blood.
Results:  In the granulomas of two of three patients with a primary immunodeficiency disorder, the cytotoxic T cells (CD8+) outnumbered the T-helper cells (CD4+) with a counted CD4+/CD8+ ratio <<1. In contrast, the granulomas in the cutaneous sarcoidosis patients showed a predominance of CD4+ cells, with CD4+/CD8+ ratios >2.
Conclusions:  A lower CD4+/CD8+ ratio was found in the cutaneous granulomas of patients with a primary immunodeficiency disorder (unclassified combined immunodeficiency, autoimmune lymphoproliferative syndrome and ataxia teleangiectasia) as compared with the patients with cutaneous sarcoidosis. The possible implications of these findings are discussed in this paper.