Treatment of Recalcitrant Acrodermatitis Continua of Hallopeau With Brodalumab

To the Editor: Acrodermatitis continua of Hallopeau (ACH) is a relatively rare chronic disorder with clinical findings of pustules and erythematous plaques on the digits.1 Although it is a variant of pustular psoriasis, it can be resistant to multiple lines of therapy. We describe for the first time a patient with recalcitrant ACH successfully treated with brodalumab, an interleukin-17 receptor A (IL-17RA) blocking antibody.

Ustekinumab for the treatment of acrodermatitis continua of Hallopeau refractory to anti-TNF agents.

Acrodermatitis continua of Hallopeau (ACH) is a variant of pustular psoriasis that is often very difficult to treat. Almost all anti-psoriatic agents have been used in the treatment of ACH. Ustekinumab, a fully human monoclonal antibody of the IgG1 class, is directed to the shared p40 subunit of cytokines IL-12 and IL-23. Herein, we present our experience of ustekinumab use in a 50-year-old man who was resistant to anti-tumor necrosis factor-α agents. Though initial therapy with ustekinumab achieved a sustained response in our patient, after a seven months of interruption, retreatment resulted in a slower and poorer response than the initial regimen. Both responses of our patient reflects: (i) the recalcitrant chronic nature of ACH in some patients, (ii) the value of ustekinumab in ACH treatment, (iii) the fact that, as with other biologics, a loss of response may also occur with ustekinumab when the treatment is interrupted. All these data provides evidence for the fact that the course of ACH is unpredictable and possibly indicate that concerning current biologics used in the treatment of ACH, we have still failed to hit the target we aimed for.

A Souvenir From France: Acrodermatitis Chronica Atrophicans Presenting in the United States.

A 70-year-old man was referred by his rheumatologist to our dermatology clinic for evaluation of dermatitis on his right arm that appeared 3 months earlier. The skin lesion was asymptomatic and the patient denied current systemic symptoms, including fever, chills, and joint pain; however, 10 months prior to this presentation he experienced arthritis in the left knee. At that time, Borrelia serology revealed positive IgG (6.07; <0.8 negative, 0.8 to 0.99 borderline, ≥1 positive) and negative IgM titers. The patient had not received treatment for Lyme disease in the past. He was referred to rheumatology for evaluation of possible Lyme disease but did not follow up until 10 months later. The arthritis has since resolved. He travels frequently to France and recalls multiple tick bites during these trips.

Is Gianotti-Crosti Syndrome Associated with Atopy? A Case-Control Study and a Postulation on the Intrinsic Host Factors in Gianotti-Crosti Syndrome.

OBJECTIVES: To investigate whether Gianotti-Crosti syndrome (GCS) in children is associated with atopy. METHODS: The setting was two outpatient clinic. Diagnoses of asthma and atopic dermatitis (AD) were made according to internationally accepted diagnostic criteria. Allergic rhinitis, atopic urticaria, and allergic conjunctivitis were diagnosed clinically. Participants were children with GCS diagnosed over the previous 5 years. For any child with GCS, we extracted the record of the subsequent age and sex pair-matched child seen for problems unrelated to the skin as controls. RESULTS: We retrieved the records of 37 pairs of study and control subjects; 28 (76%) children with GCS and 9 (24%) controls had AD (risk ratio [RR] = 3.11[95% confidence interval {CI} 1.73, 5.73]), 31 (84%) children with GCS and 19 (51%) controls had at least one atopic condition (RR = 1.63 [95% CI 1.13, 2.18]) and 11 (30%) children with GCS and 2 (5%) controls had at least three atopic conditions (RR = 5.50 [95% CI 1.29, 35.35]). CONCLUSION: GCS is significantly associated with AD and the presence of atopic conditions.

Histopathology and immunophenotype of acrodermatitis chronica atrophicans correlated with ospA and ospC genotypes of Borrelia species.

BACKGROUND: Chronic cutaneous borreliosis (acrodermatitis chronica atrophicans, ACA) is a relatively rare manifestation of borreliosis attributed mainly to Borrelia afzelii. Chronic borreliosis has been associated with ospA and ospC genotypes. Literature on molecular investigations of Borrelia in lesions of ACA is scant. METHODS: Histopathological and immmunohistochemical features in 22 biopsies of ACA (16 patients) were examined. Paraffin-embedded biopsies were analyzed with polymerase chain reaction (PCR) assays targeting ospA and ospC genes, sequencing and phylogenetic analysis. RESULTS: Genotyping of ospA identified B. afzelii, serotype 2, in 12 of 16 patients. ospC-PCR was positive in seven patients revealing genotypes Af5 (n = 4), Af2 (n = 2) and Af6 (n = 1). Histopathologically, interstitial granulomatous infiltrates (CD68 positive) were common, combined with thickened collagen bundles and band-like infiltrates of CD4 positive T lymphocytes. Plasma cells were sparse/absent in 9 of 22 specimens even on staining with CD138. On CD34-staining, interstitial fibroblasts were often reduced akin to the situation in morphea. CONCLUSIONS: With assays targeting ospA and ospC genes we confirmed from paraffin-embedded biopsies that B. afzelii, serotype 2, osp C groups Af5, Af2 and Af6 is the main cause of ACA. Specimens commonly showed a combination of band-like T-cell-rich infiltrates with interstitial granulomatous features, a pattern previously under-recognized in ACA. This finding was particularly typical for lesions infected with ospC genotype Af5.

Zinc deficiency and toxicity in pediatric practice.

PURPOSE OF REVIEW: Zinc is a commonly overlooked deficiency in developed countries, occurring in infants, children, and adolescents during critical growth periods. The purpose of this review is to present the evidence of zinc deficiencies and toxicities as well as treatment in pediatrics. RECENT FINDINGS: During the last decade, the significance of zinc deficiency in childhood growth, morbidity, and mortality has been recognized by a number of large-scale supplementation trials in underdeveloped countries. Recognition of the recent nationwide shortage of injectable zinc available for total parenteral nutrition supplementation over the last 2 years focused attention on the possibility of zinc deficiency in the United States. SUMMARY: Although primarily thought of as a problem reserved for underdeveloped countries, zinc deficiency has increasing pediatric prevalence in the USA. Zinc is an essential trace element in the body that is responsible for numerous structural, catalytic, and biochemical functions. Deficiencies can occur because of poor dietary intake, long-term parenteral nutrition without supplementation, and enteral causes such as malabsorption. Zinc deficiency is closely associated with stunting, respiratory infections, diarrhea, and dermatitis. Deficiency is hard to define solely by the serum levels. Clinicians should utilize a combination of serum zinc levels, presenting signs and symptoms, and nutritional intake via oral, enteral, and parenteral routes to accurately assess the deficiency risk and diagnosis.

Human ß-defensin 4 expression in Gianotti-Crosti.

The Gianotti-Crosti syndrome is a relatively common children dermatosis characterized by a monomorphous erythematous papular rash limited to the face and extensor surface of the arms and legs. Although the pathogenesis is still unclear, infections are considered as the most important factor. Human ß-defensins are cationic antimicrobial peptides closely related to bacterial and viral infections of many epithelia. We herein report a case of Gianotti-Crosti syndrome in a 7-year-old Caucasian girl presented with prominent eruption consisting of dome-shaped lichenoid papules on her upper and lower extremities, with spontaneous resolution. Skin biopsy revealed a dense lichenoid lymphohistiocytic infiltrate and showed strong cytoplasmic immunopositivity for human ß-defensin-4 in the stratum corneum, stratum granulosum, and stratum spinosum. Considering that ß-defensins have been described to be induced by infections, we investigated the expression of human ß-defensin-4 by immunohistochemistry in a case of Gianotti-Crosti syndrome, in order to demonstrate that it represents a cutaneous response to skin infections.

Acrodermatitis chronica atrophicans with pseudolymphomatous infiltrates.

In this study, we describe the clinicopathologic features of pseudolymphomatous infiltrates found within lesions of acrodermatitis chronica atrophicans (ACA). We studied 11 patients (10 females, 1 male, age range 60-88 years). The diagnosis of ACA in all cases was confirmed by clinicopathologic correlation and positive serology for Borrelia. Histopathologic examination revealed prominent, pseudolymphomatous inflammatory cell infiltrates in all cases, with 2 distinct patterns. Eight of 11 cases showed a band-like lymphocytic infiltrate, exocytosis of lymphocytes and a fibrotic papillary dermis, similar to features seen in mycosis fungoides. The other 3 cases showed dense, nodular-diffuse dermal infiltrates with many plasma cells and without germinal centers. The plasma cells expressed both kappa and lambda immunoglobulin light chains with a polyclonal pattern in all 3 cases. In conclusion, ACA may present with pseudolymphomatous infiltrates showing both a T-cell and, less frequently, a B-cell pattern. These lesions need to be distinguished from a cutaneous lymphoma. In the context of the knowledge of Borrelia-associated cutaneous lymphomas, follow-up seems advisable in these cases.

Lyme disease as a cause of acropapular dermatitis of childhood.

Acropapular dermatitis of childhood is a symmetric self-limited papulovesicular exanthem that classically occurs on the cheeks, extensor extremities, and buttocks in young children. The eruption of acropapular dermatitis of childhood represents a reaction to a variety of infections usually of viral origin. We present a child with typical findings of acropapular dermatitis of childhood whose serologic workup revealed an acute Lyme infection.

Chemokine signatures in the skin disorders of Lyme borreliosis in Europe: predominance of CXCL9 and CXCL10 in erythema migrans and acrodermatitis and CXCL13 in lymphocytoma.

The three skin disorders of Lyme borreliosis in Europe include erythema migrans, an acute, self-limited lesion; borrelial lymphocytoma, a subacute lesion; and acrodermatitis chronica atrophicans, a chronic lesion. Using quantitative reverse transcription-PCR, we determined mRNA expression of selected chemokines, cytokines, and leukocyte markers in skin samples from 100 patients with erythema migrans, borrelial lymphocytoma, or acrodermatitis chronica atrophicans and from 25 control subjects. Chemokine patterns in lesional skin in each of the three skin disorders included low but significant mRNA levels of the neutrophil chemoattractant CXCL1 and the dendritic cell chemoattractant CCL20 and intermediate levels of the macrophage chemoattractant CCL2. Erythema migrans and particularly acrodermatitis lesions had high mRNA expression of the T-cell-active chemokines CXCL9 and CXCL10 and low levels of the B-cell-active chemokine CXCL13, whereas lymphocytoma lesions had high levels of CXCL13 and lower levels of CXCL9 and CXCL10. This pattern of chemokine expression was consistent with leukocyte marker mRNA in lesional skin. Moreover, using immunohistologic methods, CD3(+) T cells and CXCL9 were visualized in erythema migrans and acrodermatitis lesions, and CD20(+) B cells and CXCL13 were seen in lymphocytoma lesions. Thus, erythema migrans and acrodermatitis chronica atrophicans have high levels of the T-cell-active chemokines CXCL9 and CXCL10, whereas borrelial lymphocytoma has high levels of the B-cell-active chemokine CXCL13.

[Skin manifestations of Lyme borreliosis]. / Skórne postacie boreliozy z Lyme.

Lyme borreliosis is the most common tick-borne disease which is caused by Borrelia burgdorferi and transmitted in the Poland, as well as Europe, primarily by Ixodes ticks. After inoculation spirochetes spreads in the skin, activate locally immune response mechanisms and cause characteristic skin lesions like erythema migrans, lymphadenosis benigna cutis, erythema migrans multiplex and acrodermatitis chronica atrophicans. The correct clinical diagnosis of skin lesions and antibiotic treatment is most important for regression of symptoms and prevention of late manifestations of Lyme disease.