C. Rose

Antibodies to desmogleins 1 and 3, but not to BP180, induce blisters in human skin grafted onto SCID mice.

Pemphigus and bullous pemphigoid (BP) are blistering skin diseases associated with IgG autoantibodies to desmosomal and hemidesmosomal components. When autoantibodies to desmogleins 1 and 3 from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) or rabbit antibodies against the murine hemidesmosomal component BP180 are passively transferred into neonatal mice, they induce blisters in the skin of the mice. To develop an animal model that would duplicate the findings in the skin of the patients more closely, full‐thickness human skin from healthy volunteers was grafted onto SCID mice. Injection of the purified IgG fraction from the serum of PF and PV patients led to subcorneal and suprabasal splits in the human grafts and human IgG was deposited intercellularly in the upper and lower layers of the epidermis, respectively. Interestingly, anti‐BP180 autoantibodies purified from the serum of BP patients and from a rabbit immunized with recombinant human BP180 strongly bound to the basement membrane zone of the grafts (n=32), fixed murine complement, led to the recruitment of neutrophils to the upper dermis of the graft, but did not induce subepidermal blisters. We report a novel experimental model for PF and PV which should greatly facilitate further studies to dissect the immunopathological mechanisms in these diseases. Specifically, this model can be used to identify pathogenically relevant epitopes on human desmogleins 1 and 3 and to develop novel strategies for the treatment of pemphigus. Copyright

Follicular cutaneous T-cell lymphoma: beneficial effect of isotretinoin for persisting cysts and comedones

SIR, Follicular (pilotropic) mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL) that manifests with neoplastic lymphocytes mainly in the epithelium of hair follicles. Clinical features of follicular MF include prominent lesional or perilesional comedo-like eruptions with plugged follicles and ⁄or follicular papules. Although only a small number of patients has been described thus far, follicular MF was recently suggested to be more refractory to standard therapy and associated with a worse prognosis than classical MF. While typical MF lesions usually respond well to classical treatments, comedones and epidermal cysts have been reported to be resistant in a high proportion of cases. We describe a patient with follicular MF whose lymphomatous infiltrates responded favourably to systemic treatment with oral psoralen plus ultraviolet A (PUVA) and interferon alfa. In contrast, residual extensive comedones and cysts were resistant to this treatment modality. Subsequent additional therapy with isotretinoin led to full remission of these sequelae over a period of 15 months. A 63-year-old man presented with a 3-year history of slowly progressing erythematous patches on the upper back, neck and ears with prominent cysts and comedones (Fig. 1a). Biopsy specimens from two different locations showed a dense infiltrate of atypical lymphocytes predominantly surrounding and infiltrating the hair follicles as well as the wall of the cysts while largely sparing the interfollicular epidermis. A marked dilation of several follicular infundibula as well as epidermal cysts were noted (Fig. 1b). Colloidal iron stain excluded prominent deposits of mucin in hair follicles. Immunohistology demonstrated a CD45RO+ CD4+ CD8– phenotype of the neoplastic T cells consistent with follicular MF (not shown). Full blood count, biochemical profile and b2-microglobulin levels were normal while serum lactate dehydrogenase levels were slightly elevated (250 U L; normal 120–240). The patient did not show lymph node or organ infiltration as determined by abdominal and lymph node ultrasound evaluation. The diagnosis of follicular MF was made and therapy was given with PUVA in combination with interferon alfa-2a 9 · 10 IU subcutaneously three times weekly. Within 5 months lymphomatous lesions had healed and control histology confirmed the absence of infiltrates. However, comedones and cysts persisted in the areas of previous follicular MF (Fig. 2a). We therefore initiated therapy with isotretinoin (initial dose 1 mg kg daily, with successive reduction to 0Æ2 mg kg daily) for a period of 15 months. This treatment led to a slow but steady regression of the residual cysts and comedones with complete healing over a period of 15 months in the absence of relapse of follicular MF (Fig. 2b). Only few patients with follicular MF have been reported to date. Thus, the treatment modalities utilized have been identical to those used in other types of MF, including topical corticosteroids, PUVA, nitrogen mustard, mechlorethamine, carmustine or systemic retinoids, radiotherapy, polychemotherapy, interferon alfa-2a, or photopheresis. In line with a previous report, our patient’s comedones and cysts did not respond sufficiently to the combined treatment with PUVA and interferon alfa-2a, thus requiring additional therapy for these lesions. The retinoid acitretin was not beneficial in combination with PUVA when compared with PUVA and interferon alfa-2a for the treatment of stage I or II CTCL. Oral isotretinoin decreases the size and secretion of the sebaceous glands, normalizes follicular keratinization and prevents the formation of new comedones, as well as exerting an anti-inflammatory effect. Our report suggests a potential benefit of isotretinoin as

Hornstein-Knickenberg-/ Birt-Hogg-Dubé-Syndrom Fallbericht mit Spontanpneumothorax und Aplasie der linken A. carotis interna

ZusammenfassungBei einem 36-jährigen Patienten bestanden seit einigen Jahren zentrofazial, am Hals und am Rücken multiple hautfarbene Papeln. Auch bei seinem Vater, der Schwester und fraglich auch beim Großvater väterlicherseits wurden auswärtig ähnliche Hautbefunde erhoben. Die histologische Begutachtung der Hautveränderungen in allen 3 Fällen ergab Fibrofollikulome. Zusätzlich trat bei dem Patienten im Alter von 33 Jahren ein linksseitiger Spontanpneumothorax und ein Jahr später eine Subarachnoidalblutung bei Aplasie der linken A. carotis interna auf. Der Großvater väterlicherseits war an einem metastasierenden Rektumkarzinom verstorben.Wir diagnostizierten ein Hornstein-Knickenberg-/Birt-Hogg-Dubé-Syndrom, das durch das gemeinsame Auftreten von Fibrofollikulomen und Kolonadenomen charakterisiert ist. Die vorgestellte Familie stützt die Annahme eines autosomal-dominanten Erbgangs dieses Syndroms. Neben Haut und Darm können noch weitere Organsysteme, nämlich Nieren- und Genitaltrakt, Augen und Endokrinium betroffen sein. Lungenveränderungen wurden bislang bei 6 Patienten mit diesem Syndrom beschrieben. Wir möchten mit dieser Beobachtung auf die charakteristischen Hautveränderungen des Hornstein-Knickenberg-/Birt-Hogg-Dubé-Syndroms hinweisen, die Leitsymptom maligner Tumoren und anderer Begleitsymptome sein können.AbstractA 36-year-old man presented with multiple skin-colored papules on his face, neck and back of several years duration. His father, sister and probably his grandfather suffered from similar skin lesions. The histological examination revealed fibrofolliculomas in all three cases. At the age of 33 years the patient developed a spontaneous pneumothorax, and one year later a subarachnoidal hemorrhage due to aplasia of the left carotid artery. His grandfather had died from metastatic rectal carcinoma. A diagnosis of Hornstein-Knickenberg-/ Birt-Hogg-Dubé syndrome was made, which is characterized by fibrofolliculomas and colon adenomas. Our familial observation speaks in favor of autosomal dominant transmission of the Hornstein-Knickenberg-/ Birt-Hogg-Dubé syndrome. Apart from the skin several other organs may be involved, including the kidneys, urogenital tract, eyes and endocrine system. By this report we wish to draw intention to the typical skin lesions which can be the marker for neoplasia and other characteristic associated findings.

Intertriginöse Vesikel und Pusteln bei einem 36-Jährigen

Bei einem 36-jährigen Patienten traten seit mehreren Jahren rezidivierend juckende Bläschen und Pusteln auf, die vor allem axillär,inguinal,am Rücken und den Oberarmen imponierten. Die Läsionen heilten unter Hypobzw. Hyperpigmentierungen ab. Die histologische Untersuchung einer Hautbiopsie zeigte eine subkorneale Pustel. Unter dem Verdacht einer subkornealen Pustulosis SneddonWilkinson wurde ein Therapieversuch mit Dapson eingeleitet (täglich 2 mg/kg Körpergewicht). Der Patient setzte diese Behandlung trotz Besserung des Hautbefundes wegen subjektiv empfundener Belastungsdyspnoe ab. In der Folgezeit wurde eine 12-monatige Therapie mit Azathioprin (Imurek®, täglich 2 mg/kg Körpergewicht) und Prednison (Decortin®, 5 mg/d) durchgeführt, die jedoch keine Besserung bewirkte.

Erfolgreiche Therapie eines Angiosarkoms mit liposomal verkapseltem Doxorubizin

ZusammenfassungKutane Angiosarkome sind seltene, mitunter schwierig zu diagnostizierende Gefäßtumoren endothelialer Differenzierung mit schlechter Prognose. Wir berichten über eine 85-jährige, multimorbide Patientin mit einem ausgedehnten kutanen Angiosarkom an der rechten unteren Extremität. Nach histologischer Diagnosesicherung bei zunächst klinisch untypischen Läsionen wurde angesichts des Alters der Patientin und der Ausdehnung des Tumors auf chirurgische Maßnahmen verzichtet und eine Radiatio mit Kobalt-60 eingeleitet. Hierunter kam es jedoch zur weiteren Progredienz des Tumors, sodass wir uns zu einer palliativen Chemotherapie mit liposomal verkapseltem Doxorubizin entschlossen. Sechs Therapiezyklen mit Doxorubizin (Caelyx®, 15 mg/m2 i.v. in 4-wöchigen Abständen) führten zu einer kompletten, über 6 Monate anhaltenden Remission des Angiosarkoms und wurden von der Patientin gut vertragen.Eine Chemotherapie mit liposomal verkapseltem Doxorubizin stellt eine gut verträgliche Therapieoption des Angiosarkoms dar, wenn eine Operation mit nachfolgender Radiatio nicht möglich ist bzw. versagt. Weitere Studien sind notwendig, um den Stellenwert einer solchen Therapie des Angiosarkoms zu belegen.AbstractCutaneous angiosarcoma is a rare tumor of endothelial origin, often difficult to diagnose and with an unfavorable prognosis. A 85-year-old woman presented with an extensive angiosarcoma involving her right leg. The tumor was not clinically typical but the diagnosis was confirmed histologically. Because of her age and the extent of the tumor, we elected to treat primarily with cobalt-60 irradiation. The tumor unfortunately progressed during radiation therapy, so we decided to begin palliative chemotherapy with liposome-encapsulated doxorubicin. The patient received six cycles of doxorubicin (Caelyx®, 15 mg/m2 i.v. in four-week intervals) which was well-tolerated and led to complete regression of angiosarcoma which has lasted for 6 months.Chemotherapy with liposome-encapsulated doxorubicin may represent a well-tolerable therapeutic option in cases where surgery and irradiation are not possible or fail. Further studies are necessary to prove the efficacy of doxorubicin therapy in angiosarcoma.

Subepidermal blasenbildende Autoimmundermatose mit linearen Ablagerungen von IgA und IgG

ZusammenfassungWir berichten über eine 29jährige Patientin mit einer subepidermal blasenbildenden Autoimmundermatose, die durch lineare Ablagerungen von IgA- und IgG-Antikörpern an der dermoepidermalen Junktionszone gekennzeichnet ist. Klinisch fanden sich pralle Bläschen im Gesicht, am Stamm, an den Extremitäten und an der Mundschleimhaut. Histologisch sahen wir eine subepidermale Blasenbildung und ein neutrophilenreiches Entzündungsinfiltrat. Mittels direkter Immunfluoreszenz fanden sich in der Haut der Patientin lineare IgA-Ablagerungen an der Basalmembranzone. Ungewöhnlich war jedoch der gleichzeitige Nachweis von linearen IgG- und C3-Ablagerungen, die typischerweise beim bullösen Pemphigoid vorkommen. Auch im Serum der Patientin fanden sich Autoantikörper sowohl der IgA- als auch der IgG-Klasse. Der Fall dieser Patientin bestätigt frühere Berichte, daß es bei den subepidermal blasenbildenden Autoimmundermatosen eine Untergruppe von Patienten mit gleichzeitigem Nachweis von IgA- und IgG-Antikörpern gibt, bei denen sich klinische, histologische und immunpathologische Merkmale von linearer IgA-Dermatose und bullösem Pemphigoid überlappen.AbstractA 29-year-old female patient with an autoimmune subepidermal blistering disease had linear deposits of both IgA and IgG at the basement membrane zone. Clinically, the patient presented with tense blisters on the face, trunk, extremities and oral mucosa. Histologically, we found a subepidermal blister formation and a predominantly neutrophilic infiltrate. Direct immunofluorescence showed linear deposits of IgA along the basement membrane zone, as well as linear deposits of IgG and C3 as typically found in bullous pemphigoid. Indirect immunofluorescence demonstrated circulating IgA and IgG autoantibodies. This case extends previous reports on a subgroup of patients with subepidermal blistering diseases characterized by the presence of both IgA and IgG anti-basement membrane antibodies. These patients reveal clinical, histological and immunopathological features of linear IgA disease and bullous pemphigoid.

Subkutanes pannikulitisartiges T-Zell-Lymphom

Histopathology, immunohistochemical, and molecular genetic findings revealed the diagnosis of subcutaneous panniculitis-like T-cell-lymphoma in two patients, aged 44 and 70 years. The clinical morphology of the lymphoma manifestations showed varied significantly. One patient presented with a singular erythematous nodule in the chin region. The other patient suffered from extended plate-like resistances and atrophy of the face, upper arms and left breast. Hemophagocytic syndrome was not present in either patient. Prognosis of subcutaneous panniculitis-like T-cell lymphoma without associated hemophagocytic syndrome is reported to be favorable. Radiotherapy of the singular lesion on the chin and systemic corticosteroids of the extended plaques induced complete remission in both patients.

Erythema migrans arciforme et palpabile

A 39-year-old man presented with an annular clearly palpable erythema on the décolleté. Based on clinical and histopathological findings, palpable migratory arciform erythema was diagnosed. This skin condition is classified as a rare type of T-cell pseudolymphoma. It is still a matter of debate whether palpable migratory arciform erythema is a specific entity or a clinical variant of lymphocytic infiltration of the skin (Jessner-Kanof). Topical corticosteroids or oral antibiotics are generally used. In our patient, UV-A1 therapy led to a complete regression of the lesions.ZusammenfassungWir berichten über einen 39-jährigen Patienten mit einem anulären, deutlich palpablen Erythem am vorderen Dekolletee. Aufgrund der klinischen und histopathologischen Befunde wurde die Diagnose eines Erythema migrans arciforme et palpabile gestellt, einer seltenen Form eines T-Zell-Pseudolymphoms. Ob es sich um eine Entität oder eine klinische Variante der „Lymphocytic infiltration of the skin Jessner-Kanof“ handelt, ist umstritten. Zur Behandlung werden in der Regel topische Glukokortikoide oder orale Antibiotika eingesetzt. Die von uns durchgeführte UV-A1-Therapie führte zu einer vollständigen Rückbildung des klinischen Befundes.AbstractA 39-year-old man presented with an annular clearly palpable erythema on the décolleté. Based on clinical and histopathological findings, palpable migratory arciform erythema was diagnosed. This skin condition is classified as a rare type of T-cell pseudolymphoma. It is still a matter of debate whether palpable migratory arciform erythema is a specific entity or a clinical variant of lymphocytic infiltration of the skin (Jessner-Kanof). Topical corticosteroids or oral antibiotics are generally used. In our patient, UV-A1 therapy led to a complete regression of the lesions.

Subkutanes pannikulitisartiges T-Zell-Lymphom@@@Subcutaneous panniculitis-like T-cell lymphoma: Zwei Kasuistiken@@@Two case reports

Histopathology, immunohistochemical, and molecular genetic findings revealed the diagnosis of subcutaneous panniculitis-like T-cell-lymphoma in two patients, aged 44 and 70 years. The clinical morphology of the lymphoma manifestations showed varied significantly. One patient presented with a singular erythematous nodule in the chin region. The other patient suffered from extended plate-like resistances and atrophy of the face, upper arms and left breast. Hemophagocytic syndrome was not present in either patient. Prognosis of subcutaneous panniculitis-like T-cell lymphoma without associated hemophagocytic syndrome is reported to be favorable. Radiotherapy of the singular lesion on the chin and systemic corticosteroids of the extended plaques induced complete remission in both patients.

Granulomatöse periorifizielle Dermatitis der Kindheit

CASE REPORT A 14-year-old patient of African ancestry presented with multiple papules in the perioral, perinasal and periocular areas. Histopathology showed sarcoidal granulomas. DIAGNOSIS After exclusion of systemic sarcoidosis, the diagnosis of childhood granulomatous periorificial dermatitis was made. THERAPY Topical treatment with erythromycin resulted in complete regression. CONCLUSION Childhood granulomatous periorificial dermatitis is mainly observed in dark-skinned children of African, Caribbean, or Asian origin. The nosological position of the dermatosis is controversial. Originally classified as sarcoidosis, childhood granulomatous periorificial dermatitis is now generally regarded as a special form of perioral dermatitis.ZusammenfassungFallbeschreibungBei einem 14-jährigen Patienten, mütterlicherseits afrikanischer Abstammung, entwickelten sich überwiegend gruppiert stehende Papeln perioral, perinasal und periokulär.DiagnoseHistopathologisch zeigten sich sarkoidale Granulome. Bei Ausschluss einer systemischen Sarkoidose wurde die Diagnose einer granulomatösen periorifiziellen Dermatitis der Kindheit gestellt. TherapieUnter lokaler Behandlung mit Erythromycin kam es zu einer vollständigen Rückbildung des Befundes. SchlussfolgerungDie granulomatöse periorifizielle Dermatitis der Kindheit wird hauptsächlich bei Kindern mit dunkel pigmentierter Haut beobachtet, die aus Afrika, der Karibik oder Asien stammen. Die nosologische Stellung der Dermatose ist umstritten. Ursprünglich als Sarkoidose eingeordnet, wird die granulomatöse periorifizielle Dermatitis der Kindheit heute überwiegend als Sonderform der perioralen Dermatitis angesehen.AbstractCase reportA 14-year-old patient of African ancestry presented with multiple papules in the perioral, perinasal and periocular areas. Histopathology showed sarcoidal granulomas. DiagnosisAfter exclusion of systemic sarcoidosis, the diagnosis of childhood granulomatous periorificial dermatitis was made. TherapyTopical treatment with erythromycin resulted in complete regression. ConclusionChildhood granulomatous periorificial dermatitis is mainly observed in dark-skinned children of African, Caribbean, or Asian origin. The nosological position of the dermatosis is controversial. Originally classified as sarcoidosis, childhood granulomatous periorificial dermatitis is now generally regarded as a special form of perioral dermatitis.