2017 July-December; 5(3-4): 111–114. ISSN: 2282-4103
Published online 2018 March 23. doi: 10.11138/cderm/2017.5.3.111.

Localized sarcoidosis in an old tattoo: Illustrating the principle of locus minoris resistentiae

Alexandra J. Coromilas,corresponding author1 Ruth K. Foreman,2 and Steven T. Chen1,3

1Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA
2Department of Pathology, Massachusetts Hospital, Harvard Medical School, Boston, USA
3Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA

corresponding authorCorresponding author.

Address for correspondence: Alexandra Coromilas, 55 Fruit Street, Gray 7-730, Boston, MA 02114, USA, E-mail: acoromilas@partners.org

Summary

Cutaneous manifestations of sarcoidosis are common but varied in clinical presentation. We present a case of a patient with history of systemic sarcoidosis who presented with firm papules within multiple old tattoos. Pathology of one lesion revealed granulomatous infiltration consistent with sarcoidosis within an old tattoo. The patient was also found to have erythema nodosum, hilar lymphadenopathy, and arthralgias, and was diagnosed with Lofgren syndrome. This case of cutaneous sarcoid manifesting in an old tattoo illustrates the principle of locus minoris resistentiae (LMR). We review the pathophysiology of LMR, including the concept of the immunocompromised cutaneous district and cutaneous mosaicism.

Keywords: sarcoidosis, tattoo, locus minoris resistentiae

Case report

A 33-year-old man with a five-year history of sarcoidosis, diagnosed by pathology of a hilar lymph node, presented with four weeks of arthralgias and new skin lesions. Prior to current presentation, his sarcoidosis was in remission without any active treatment. He was referred to dermatology for further evaluation of his skin lesions. Dermatology consultation revealed firm papules involving multiple tattoos on the patient’s neck, arm, and wrist (Figure 1). All tattoos had been placed over ten years prior to this visit, also antecedent to first diagnosis of sarcoidosis. The patient was also found to have tender nodules with overlying erythema on the lower legs thought to be consistent with erythema nodosum (EN). Given the constellation of EN, arthralgias, and the patient’s known history of sarcoidosis, he was diagnosed with likely Lofgren syndrome, and a chest X-ray obtained confirmed hilar lymphadenopathy. A biopsy of a lesion on the forearm revealed dermal granulomatous dermatitis with peripheral lymphocytes and scattered eosinophils, consistent with cutaneous sarcoidosis within a tattoo (Figure 2). A granulomatous response to tattoo ink could not be ruled out, however thought unlikely given the clinical context of this new skin eruption. He was started on low dose prednisone, which resulted in improvement in his arthralgias, however his skin lesions persisted. He was initiated on topical betamethasone for the skin lesions, and in follow-up was found to have improved cutaneous disease.

Figure 1Figure 1
Multiple papules localized to neck tattoo (a) and arm tattoo (b).
Figure 2Figure 2
At low power (a), there is a dermal granulomatous infiltrate with admixed pigment. Higher power magnification (b) reveals dermal granulomas composed of epithelioid histiocytes and giant cells with a sparse lymphocytic inflammatory infiltrate. At this (more ...)

This case of cutaneous sarcoidosis in an old tattoo illustrates the principle of locus minoris resistentiae (LMR), the phenomenon of skin lesions presenting at sites of reduced integrity. With the onset of Lofgren syndrome in this patient, it was notable that the only cutaneous lesions outside of EN were found in old tattoos, and normal skin remained uninvolved.

Discussion and review of the literature

Locus minoris resistentiae is a phenomenon seen throughout many fields of medicine, though it is particularly prominent in dermatology. LMR has been referred to as the medical “Achilles heel” creating vulnerability to disease. The concept of cutaneous LMR dates back to a review of 13 patients in 1982 (1). These patients developed irritant or asteatotic dermatitis localized to previously injured areas of the skin. The hypothesis was that the damaged skin lost normal structures and underwent changes including less water content, abnormal corneocyte arrangement, altered barrier function, reduced production of sebum, and decreased perfusion, resulting in diminished ability to withstand encountered stresses (1). Since then, other cases that illustrate cutaneous LMR have been reported in the literature, but the underlying pathophysiology has not been fully elucidated.

LMR can be classified into two distinct dermatologic phenomena, isomorphic and isotopic reactions (Table 1). The quintessential isomorphic reaction, Köbner phenomenon, is described extensively in the literature. The recognition of the Köbner phenomenon dates back to 1876 when Heinrich Köbner reported a patient with psoriasis who developed a new psoriatic lesion at the site of a horse bite (2). The mechanism underlying the Köbner phenomenon is felt to be epidermal injury with associated dermal changes, including microlesions of sensory nerve endings, endothelial mast cell infiltration, and dermal foci of microscarring (2). These aggregate changes result in a microenvironment vulnerable to appearance of new skin lesions. It has been estimated that up to forty-nine diseases have the potential to undergo köbnerization (1). The most commonly described isotopic reaction occurs in patients with preceding herpes infection, known as Wolf’s post herpetic isotopic response (3). The subsequent response is typically a granuloma annulare-like reaction. Although the initial cases were related to prior herpetic infection, isotopic response can be triggered by a broad spectrum of clinical and pathologic diagnoses including infectious, inflammatory, and malignant etiologies (4).

Table 1Table 1
Examples of Isomorphic11 and Isotopic2,12 reactions.

Despite the multitude of cases illustrating LMR, the shared underlying pathophysiology is not completely understood. In 2009, Ruocco et al. introduced a concept known as immunocompromised cutaneous district (ICD), which refers to a localized region of immune dysregulation resulting in susceptibility to a variety of inflammatory skin disorders (5). The proposed mechanisms include impaired lymphatic drainage, resulting in abnormal lymphocyte trafficking, and damage to sensory nerve fibers, resulting in altered neuropeptide release (2). The secretion of neuropeptides such as substance P, vasoactive intestinal peptide, and somatostatin modulate epidermal and dermal immune cells, resulting in immune dysfunction and inflammatory reaction (6). This concept can be applied to Wolf’s post herpetic isotopic response. Schwartz et al. hypothesize that viral damage to sensory nerves affect neuropeptide release such as vasoactive intestinal peptide that interact with immune cells and modulate the cutaneous immune response. This alteration then predisposes the site of viral infection to future disease (7). In addition to herpetic infection, other examples of inflammatory skin changes resulting in ICD include stasis, radiation, burn, trauma, tattooing, and vaccination. The alteration of the immune system allows for vulnerability of that region to infection, malignancy, or immunologic disorders depending on the balance of cytokines and neurotransmitters infiltrating that specific area (2). According to Ruocco et al., this vulnerability can manifest within weeks, months, or years.

Tattoos represent an ICD predisposed to malignant, infectious, and inflammatory conditions (8). Cell mediated reactions that occur within tattoos are varied in time of onset, morphology, and presence or absence of associated systemic response. Histologically, decomposed pigments from tattoos can be found within lymph nodes proximal to tattoo sites, perhaps explaining the formation of the ICD via disruption in lymphatic drainage. Granulomatous infiltrates associated with tattooing have been reported in the literature since the 1950s. Most granulomatous infiltrates represent foreign-body reaction (8), which is difficult to distinguish from sarcoidosis. Notably, it has been estimated that of patients who are diagnosed with cutaneous sarcoidosis within tattoos, 74% is ultimately also diagnosed with the systemic form of the disease (9). Sarcoid granulomatous cutaneous lesions have also been reported in association with herpes zoster infection, dermal vaccination sites, and scars such as surgical sites. The proposed pathophysiology for development of granulomatous inflammation within an ICD includes both overactive and inhibited immune response, retention of exogenous antigen or foreign body, and altered neural signaling (9).

Although environmental factors are certainly key to the pathophysiology of LMR, one must also consider an underlying genetic predisposition. Al-Rohil et al., in their review of cutaneous mosaicism, provide a hypothesis that mosaicism creates a genetic predisposition to LMR. Cutaneous mosaicism is a biologic phenomenon in which two or more different cell populations exist with distinct genoptypes and phenotypes (10). These discrete skin regions have structural and immunologic properties that are thought to predispose to certain skin diseases, providing a genetic substrate for LMR. This can manifest in previously normal appearing skin that then acquires a disease, as exemplified by inflammatory and sclerosing dermatoses following lines of Blaschko. Cutaneous disorders can also arise in areas of preexisting mosaicism, such as inflammatory dermatoses or acne superimposed on an epidermal nevus or Becker’s nevus (10).

Our case of tattoo sarcoidosis represents an isotopic reaction that illustrates the phenomenon of locus minoris resistentiae. The concepts of immunocompromised cutaneous district and cutaneous mosaicism are helpful in understanding the pathophysiology of LMR. Further research is needed to better define the “common denominator” fundamental to cases of locus minoris resistentiae.

Footnotes

Disclosure

Dr. Coromilas, Dr. Foreman, and Dr. Chen did not receive financial support for this publication.

References
1.
Schiavo AL, Ruocco E, Russo T, Brancaccio G. Locus minoris resistentiae: An old but still valid way of thinking in medicine. Clin Dermatol. 2014 Sep–Oct;32(5):553–556.
2.
Caccavale S, Kannangara AP, Ruocco E. Categorization of and comments on isomorphic and isotopic skin reactions. Clin Dermatol. 2017 Jan–Fev;35(1):105–110.
3.
Ruocco V, Ruocco E, Ghersetich I, Bianchi B, Lotti T. Isotopic response after herpesvirus infection: an update. J Am Acad Dermatol. 2002;46:90–94.
4.
Ruocco V, Ruocco E, Brunetti G, Russo T, Gambardella A, Wolf R. Wolf’s postherpetic isotopic response: Infections, tumors, and immune disorders arising on the site of healed herpetic infection. Clin Dermatol. 2014 Sep–Oct;32(5):561–568.
5.
Ruocco V, Brunetti G, Puca RV, et al. The immunocompromised district: a unifying concept for lymphedematous, herpes-infected and otherwise damaged sites. J Eur Acad Dermatol Venereol. 2009;23:1364–1373.
6.
Misery L. Skin, immunity and the nervous system. Br J Dermatol. 1997;137:843–850.
7.
Piccolo V, Baroni A, Russo T, Schwartz RA. Ruocco’s immunocompromised cutaneous district. Int J Dermatol. 2016 Feb;55(2):135–141.
8.
Huynh TH, Jackson JD, Brodell RT. Tattoo and vaccination sites: Possible nest for opportunistic infections, tumors, and dysimmune reactions. Clin Dermatol. 2014 Sep–Oct;32(5):678–684.
9.
Schiavo AL, Ruocco E, Gambardella A, O’Leary RE, Gee S. Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas. Clin Dermatol. 2014 Sep–Oct;32(5):646–653.
10.
Al-Rohil RN, Leung D, Carlson A. Congenital vulnerability of cutaneous segments arising from skin mosaicism: A genetic basis for locus minoris resistentiae. Clin Dermatol. 2014 Sept–Oct;32(5):577–91.
11.
Weiss G, Shemer A, Trau H. The Koebner phenomenon: review of the literature. J Eur Acad Dermatol Venereol. 2002 May;16(3):241–248.
12.
Mahajan R, De D, Nahar Saikia U. Wolf’s isotopic response: Report of a case and review of the literature. Indian J Dermatol. 2014 May–June;59(3):275–282.