Washington University School of Medicine Digital Commons@Becker Open Access Publications 2018 Granulomatous dermatitis as a postherpetic isotopic response in immunocompromised patients: A report of 5 cases William H. McCoy Washington University School of Medicine in St. Louis Elaine Otchere Washington University School of Medicine in St. Louis Amy C. Musiek Washington University School of Medicine in St. Louis Milan J. Anadkat Washington University School of Medicine in St. Louis Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation McCoy, William H.; Otchere, Elaine; Musiek, Amy C.; and Anadkat, Milan J., ,"Granulomatous dermatitis as a postherpetic isotopic response in immunocompromised patients: A report of 5 cases." JAAD Case Reports.4,8. 752-760. (2018). https://digitalcommons.wustl.edu/open_access_pubs/7169 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. CASE SERIES Granulomatous dermatitis as a postherpetic isotopic response in immunocompromised patients: A report of 5 cases William H. McCoy 4th, MD, PhD,a,b,c Elaine Otchere, BS,a Amy C. Musiek, MD,a,b,c and MilanJ.Anadkat,MDa,b,c Saint Louis, Missouri Key words: Chronic lymphocytic leukemia; granuloma annulare; granulomatous dermatitis; immunocom- promised district; immunodeficiency; immunocompromise; immunosuppression; isotopic response; locus minoris resistentiae; postherpetic isotopic response; Wolf’s isotopic response. INTRODUCTION Abbreviations used: Granulomatous dermatitis (GD) describes disor- ders in which mixed inflammatory infiltrates AML: acute myelogenous leukemia CLL: chronic lymphocytic leukemia composed primarily of histiocytes invade the skin. GA: granuloma annulare The pathogenesis of GD is unknown; however, GD GD: granulomatous dermatitis has been noted to occur in areas previously affected HSV: herpes simplex virus 1 MM: multiple myeloma by trauma, sun damage, or infection. When GD PHIR: postherpetic isotopic response presents at the same site of a healed, unrelated skin PHIR-GD: postherpetic isotopic response- disease, it falls within the category of a Wolf’s isotopic granulomatous dermatitis 2 PHN: postherpetic neuralgia response. The regional restriction of a Wolf’s iso- SCT: stem cell transplant topic response is proposed to occur due to an area of SLE: systemic lupus erythematous localized immunocompromise known as an immu- SS: Sjogren syndrome VZV: varicella zoster virus nocompromised district.3 This immunocompromised district is believed to result from various types of cutaneous damage that hinder lymph circulation, like chronic regional lymphedema or prior herpes virus weeks.6,7 The presence of viral DNA in some lesions infection (eg, varicella zoster virus [VZV] and herpes has led to the proposal that VZV glycoproteins (gpI/ 3 simplex virus [HSV]). Postherpetic isotopic response II) may still be expressed at a sufficient level to initiate (PHIR) is the most commonly reported isotopic granuloma formation.8 response, and more cases of PHIR-GD have been Since the first report of granuloma annulare (GA) 3 reported than any other type of isotopic response. It as an isotopic response,9 38% of the 32 cases have can occur within the same dermatomal distribution been reported in the setting of immunocompro- either immediately after primary lesion resolution mise.10 We now add 5 unreported cases and 16 [ 3 (VZV HSV) or many years later. Persistent VZV literature cases (not reviewed in prior meta-analyses) DNA has been detected in PHIR lesions within of immunocompromised PHIR-GD. Our review of 4,5 4 weeks after an acute episode but not after 7 the literature has also added 23 cases of From the Department of Medicine,b Division of Dermatology,c 660 S Euclid, Campus Box 8123, St. Louis, MO 63110. E-mail: Washington University School of Medicine.a [email protected]. Funding sources: None. JAAD Case Reports 2018;4:752-60. Conflicts of interest: Dr Anadkat has received honoraria as a 2352-5126 speaker and/or consultant from Aspire Bariatrics, Amgen, Ó 2018 by the American Academy of Dermatology, Inc. Published AstraZeneca, Biogen, Bristol-Myers Squibb, Eisai, ImClone, and by Elsevier, Inc. This is an open access article under the CC BY- Therakos. He has also served as an investigator for Biogen, NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ Hana Biosciences, Vanda Pharmaceuticals, and Xoma. Elaine 4.0/). Otchere and Drs McCoy and Musiek have no conflicts to https://doi.org/10.1016/j.jdcr.2018.05.024 disclose. Correspondence to: William H. McCoy 4th, MD, PhD, Department of Medicine, Division of Dermatology, Washington University, 752 JAAD CASE REPORTS McCoy et al 753 VOLUME 4, NUMBER 8 Fig 1. Clinical and histologic images. Four of the immunocompromised patients with granulomatous PHIR from this case series are shown with their clinical photographs above and the corresponding H&E pathology immediately below. Inset images show magnified areas of rash/histology. Immunocompromise etiology and microscopic magnifications are listed. No clinical/histologic images were available for the heart transplant subject in our case series. nonimmunocompromised PHIR-GD. Our analysis of appeared in the same dermatome (Fig 1; SLE1SS) 33 immunocompromised and 43 immunocompetent complicated by severe postherpetic neuralgia (PHN) cases highlights PHIR-GD associations with immu- and trigeminal trophic syndrome with ulceration and nocompromise, chronic lymphocytic leukemia superinfection (methicillin-resistant Staphylococcus (CLL), and male sex. aureus, Candida keratitis). Biopsy found no viral cytopathic changes (Fig 1; SLE1SS). HSV/VZV assays METHODS were negative. She received valacyclovir, corticoste- We conducted a retrospective study of 5 immu- roids (topical, intralesional, oral), and calcineurin nocompromised PHIR-GD patients at Barnes Jewish inhibitors (tacrolimus, pimecrolimus) for her PHIR- Hospital in St Louis, Missouri between 2008 and GD. Her PHN required oral gabapentin, pregabalin, 2015. Through a literature search of PubMed, we duloxetine, hydroxyzine, and topical lidocaine. reviewed all previous cases of PHIR-GD. Search Autoimmune treatments were replaced with abata- terms included Wolf’s isotopic response, postherpetic cept 6 months after PHIR-GD onset. Over 19.5 isotopic response, granulomatous dermatitis, granu- months, her cutaneous disease and PHN significantly loma annulare, and perturbations of these terms. improved, but her PHN never resolved completely. References from the identified literature were used to expand our search. Case 2 A 56-year-old white man with a history of acute RESULTS myelogenous leukemia (AML) treated with chemo- Case 1 therapy and unrelated donor stem cell transplant A 53-year-old white woman with systemic lupus (SCT) later complicated by chronic graft-versus-host erythematosus (SLE), Sjogren€ syndrome (SS), and disease presented for suture removal after Mohs IgM deficiency on methotrexate, Plaquenil, predni- micrographic surgery for squamous cell carcinoma sone, and sulfasalazine presented with right V1 of the left side of the forehead. He was found to have dermatome VZV reactivation. Treatment included VZV reactivation of the left V1 dermatome. He valacyclovir, tobramycin ophthalmic ointment, and received intravenous acyclovir, oral valacyclovir, gabapentin. Less than a month after the lesions and gabapentin for PHN. Less than a month later, resolved, an erythematous, alopecic plaque an erythematous, sclerotic plaque developed in the 754 McCoy et al JAAD CASE REPORTS SEPTEMBER 2018 same dermatome consistent with GD on biopsy (Fig annular pattern developed in a left-sided C5-8 dis- 1; AML1SCT). He was treated topically (desonide, tribution consistent with PHIR-GD (Fig 1; CLL). pimecrolimus) and orally (valacyclovir, prednisone, Biopsy found superficial and deep perivascular minocycline, dicloxacillin). PHIR-GD skin lesions loose granulomas and lymphocytes (Fig 1; CLL). and PHN persisted despite treatment at 1-year Gram, Grocott methenamine silver stain, and Fite follow-up. stains were negative. Clobetasol cream improved her PHIR-GD by her follow-up at 4 months. Case 3 A 57-year-old African-American woman with a Summary of reported cases history of multiple myeloma (MM) treated with These 5 cases were integrated into a review of all chemotherapy followed by autologous SCT pre- published immunocompromised PHIR-GD clinical sented with right upper extremity (dermatomes C5- and histologic data (Supplemental Figs 1 and 2). For C6) VZVreactivation. She was treated with high-dose comparison, PHIR granulomatous vasculitis and acyclovir. Two weeks later, flat-topped, violaceous, folliculitis cases were summarized separately polygonal papules appeared among resolving VZV (Supplemental Figs 3 and 4). The average age of lesions (Fig 1;MM1SCT). Biopsy found poorly PHIR-GD presentation was similar in immunocom- formed epithelioid granulomas in the superficial promised patients (65 6 11 years) and immunocom- dermis with extension to the dermoepidermal junc- petent patients (59 6 18 years). Although most tion and no lichenoid infiltrate or viral cytopathic PHIR-GD cases were initiated by VZV ([96%), HSV change (Fig 1;MM1SCT). Grocott methenamine was identified in 9% of immunocompromised PHIR- silver stain, and acid-fast bacilli stains were negative. GD cases.