From SARS-CoV-2 hematogenous spreading to endothelial dysfunction: clinical-histopathological study of cutaneous signs of COVID-19.

BACKGROUND: To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted. CASE PRESENTATION: The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died. The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing. CONCLUSIONS: The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.

Blisters Induced by PUVA: A Report of 5 Cases. / Ampollas inducidas por PUVA. Presentación de 5 casos.

Blisters associated with PUVA treatments are an adverse effect of photochemotherapy that has been reported in the literature. Asymptomatic blisters appear spontaneously mainly on the lower limbs and resolve without treatment. The differential diagnoses to consider include a phototoxic reaction, pseudoporphyria, and PUVA-induced bullous pemphigoid. We describe the clinical and histologic features in 5 cases of blistering secondary to PUVA treatment. If this adverse effect is accurately diagnosed, photochemotherapy need not be interrupted, and unnecessary diagnostic procedures and additional treatments can be avoided.

Topical nitrogen mustard therapy in patients with mycosis fungoides or parapsoriasis.

BACKGROUND: Topical nitrogen mustard is a chemotherapeutic agent used in treatment of mycosis fungoides (MF). OBJECTIVE: To evaluate the response and side effects in patients with MF and parapsoriasis treated with topical nitrogen mustard. METHODS: A retrospective study of treatment response in 116 patients diagnosed with MF and 71 patients with parapsoriasis and treated with topical nitrogen mustard from 1991 to 2009. RESULTS: Overall response rate and complete response (CR) rate was 91.4% and 53.4% in patients with MF and 90.1% and 40.8% in patients with parapsoriasis, respectively. Relapse following CR was observed in 67.7% in patients with MF and 62.1% in patients with parapsoriasis. Freedom-from-relapse was higher in patients with T1-T2 than in T3 disease (P < 0.01). Progressive disease (PD) occurred in 25.0% and 26.8% in patients with MF and parapsoriasis, respectively. Progression-free survival was similar in patients with T1-T2 compared with T3 (P = 0.79) and T4 disease (P = 0.22) and lower in patients with parapsoriasis with <10% than >10% skin involvement (P = 0.05). CONCLUSION: The present study confirms that topical nitrogen mustard is a safe and effective therapy. The treatment response in patients with parapsoriasis was not statistically different from the response in patients with MF. This supports, that parapsoriasis is not a distinct entity, but an early stage of MF. Nitrogen mustard should therefore still be considered as an important treatment modality in patients with early stages (parapsoriasis) and later stages of MF either as monotherapy or in combination with other topical or systemic therapies.

Clinical analysis of 48 cases of inverse psoriasis: a hospital-based study.

Inverse psoriasis, rare in clinical practice, refers to psoriasis only or mainly occurring at flexural sites, such as the axilla, antecubital fossae, popliteal fossae, and inguinal creases. It is also known as flexural psoriasis. With a total collection of psoriatic cases from September 2002 to December 2003 at Xijing hospital, we made a retrospective analysis of the disease history, clinical characteristics, and treatment of the patients affected with inverse psoriasis. The results showed that the major clinical manifestations of inverse psoriasis were sharply demarcated erythematous plaques with varying degrees of infiltration and minimal or no scales. Affected areas often involve the groin, axilla, genitals, and umbilicus. The disease responds well to the narrow band UVB therapy. Compared with common psoriasis, inverse psoriasis has similar and unique characteristics in terms of the affected areas, clinical symptoms, and responses to the treatment.

Evaluation of a 1-h exposure time to mechlorethamine in patients undergoing topical treatment.

BACKGROUND: Mechlorethamine is frequently used in the treatment of cutaneous lymphoma, but its application is limited in 30-80% of cases because of cutaneous intolerance. Reducing the concentration to avoid this side-effect has been only modestly successful. OBJECTIVES: To investigate whether a shorter application period could reduce the frequency of intolerance. METHODS: In an open prospective study in 39 patients with cutaneous T-cell lymphoma or parapsoriasis, mechlorethamine was applied according to the usual practices of the participating physicians (number of weekly applications, treatment confined to lesions or performed over the entire body) and then washed off after 1 h in all cases. RESULTS: Cutaneous intolerance was observed in 19 of 39 patients (49%). Six of these patients showed allergic contact dermatitis to mechlorethamine after a mean period of 9.3 weeks, while the other 13 developed irritant contact dermatitis after a longer period. Cutaneous intolerance did not differ significantly according to the number of applications per week or the extent of body area treated. The therapeutic response rate was 69%, and no difference in therapeutic efficacy was noted between daily and intermittent applications. CONCLUSIONS: Comparison with published studies showed no significant difference in the number of cases of cutaneous intolerance after short-term application, although their occurrence was delayed. Therapeutic response was decreased appreciably by short-term application as compared with results in the literature.

PUVA-induced lichen planus pemphigoides.

A 72-year-old woman had suffered from parapsoriasis en plaque (large plaque type) controlled by topically applied psoralen ultraviolet A (PUVA) therapy. The parapsoriasis lesions gradually disappeared, but numerous tiny red papules with pruritus appeared over the forearms and lower legs 120 days after starting PUVA therapy. These papules developed to form violaceous plaques. Histological findings demonstrated the characteristics of lichen planus. Two months later, tense bullae developed on the plaques and on uninvolved skin of the limbs. These were subepidermal, with linear deposits of IgG and C3 along the basement membrane zone (BMZ) in immunofluorescence of peribullous skin, and immunodeposits of type IV collagen along the floor of the bullae. We therefore, diagnosed lichen planus pemphigoides (LPP). Using systemic and topical steroid therapy, the lesions rapidly resolved and there has been no recurrence. This case suggests that the combination of basal cell injuries caused by chronic inflammation and PUVA therapy could expose BMZ components to autoreactive lymphocytes and induce LPP.

[PUVA-induced acro-bullous dermatosis]. / PUVA-induzierte akrobullöse Dermatose.

PUVA-induced acrobullous dermatosis is characterized by the occurrence of blisters on the acral extremities during PUVA therapy. The tense blisters apparently arise as a result of PUVA damage to the epidermodermal cohesion coupled with friction or trauma. They must be distinguished from phototoxic reactions induced either by UVA over-dosage or excessive psoralen uptake. We report on, two cases of acrobullous PUVA-induced dermatosis, discussing clinical features, pathophysiological aspects and differential diagnosis.

Therapeutic options for erythroderma.

In this work we will discuss some of the dilemmas and therapeutic options in the treatment of patients with erythroderma. We will mention treatment modalities for psoriatic erythroderma and review briefly one illustrative case in which a new experimental approach was utilized.

Treatment of a case of mycosis fungoides and one of parapsoriasis en plaque with topical PUVA using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin.

A case of plaque stage mycosis fungoides and one of parapsoriasis en plaque were treated with topical PUVA therapy using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin (TMA). Both patients showed complete clearance of eruptions within 16 treatments. The therapeutic effectiveness of TMA was confirmed by the fact that those eruptions exposed to UVA alone, without TMA application, showed slower and less significant improvement. Histologically, dermal infiltrates of mycosis cells and associated epidermotrophism disappeared almost completely in response to TMA PUVA. No side effects or changes in values in laboratory examinations were observed during treatment.

[Phototherapy of parapsoriasis]. / Fototherapie der Parapsoriasis.

The effectiveness of photo(chemo)therapy was tested on 69 patients with different forms of parapsoriasis (parapsoriasis guttata, n = 14; pityriasis lichenoides et varioliformis acuta, n = 6; and parapsoriasis en plaques, n = 49). The forms of parapsoriasis differed in their response to phototherapy and in their relapse rates. Whereas parapsoriasis guttata can be regarded as a definite indication for UVA therapy, much higher UVA doses are required for pityriasis lichenoides et varioliformis and the probability of relapses is higher. It was not possible to interrupt the relapsing course of parapsoriasis en plaqes in the majority of patients. Relapses occurred within 7 months in 63.2% of the cases. A healing effect that lasted for more than one year was achieved only in 18 patients.

[Mucha-Habermann disease. Description of a case in childhood]. / La malattia di Mucha-Habermann. Descrizione di un caso in età pediatrica.

The authors report a case of Mucha-Habermann disease in childhood. Mucha-Habermann disease is not a very well known, though not infrequent, disease. It is characterized by recurrent erythematous-papular-vesicular skin lesions associated with arthralgia or arthritis or large joints. Prognosis is generally favourable although an evolution towards Pityriasis Lichenoides Chronica and/or Mycosis Fungoides is possible. There are not specific laboratory findings for this form. Diagnosis is essentially based on histology showing an immunopathogenetic vasculitis. At the present time there is not a safe therapy for the disease; there are however indications for the use of Erythromycin and we followed these in our therapy with positive results.

Photochemotherapy in cutaneous T cell lymphoma and parapsoriasis en plaques. Long-term follow-up in forty-three patients.

Forty-three patients with clinical plaque- and tumor-stage mycosis fungoides, the erythrodermic/Sézary syndrome variant of mycosis fungoides, and parapsoriasis en plaques were treated with oral psoralens and ultraviolet A (PUVA). Pretreatment skin biopsies, evaluated by light microscopy, revealed seventeen diagnostic, seventeen suggestive, and nine nonspecific specimens. Clinical and histologic parameters were followed for an average of 38.4 months (range, 4-67 months). Twenty-five patients had complete clearing, and fourteen did not respond. Most patients in the complete-response group had either plaque lesions of mycosis fungoides or parapsoriasis en plaques prior to PUVA. Most patients in the no-response group had either tumor lesions or the erythrodermic/Sézary mycosis fungoides at the start of PUVA. In the no-response group the treatment modalities used prior to PUVA were twice the number used in the complete-response group. Patients in the complete-response group had clearing of their lesions after an average PUVA dose of 117 joules/cm2. Relapse occurred in seventeen patients after an average remission time of 6.3 months and responded to additional PUVA. Patients whose skin remained clear after the first course of PUVA continued to have clear skin for up to 58 months, with an average complete remission of 29.5 months by the end of the study period. Histologic evaluation before PUVA and at clearing revealed a definite trend toward a normal microscopic picture, but at least a mild inflammatory infiltrate usually persisted. At the end of the study period, the lesions of ten patients had entirely cleared for an average of 44 months, the lesions of five had cleared during a second course of PUVA, five had stable limited-plaque disease while receiving maintenance PUVA, eleven were undergoing electron beam radiation therapy or chemotherapy for progressive disease, ten had died, and two patients were lost to follow-up. Therefore, in the early stage of mycosis fungoides, PUVA may induce significant disease-free intervals. Prior treatment with a variety of modalities, the patient's age, and/or the duration of disease may affect response to PUVA.