Generalized purpuric rash as a clinical presentation of monkeypox infection in a mild immunosuppressed HIV patient: case report.

To the editor:

A multi-country outbreak of monkeypox infection starting in May 2022 has rapidly spread throughout the USA and Western Europe with more than 18.000 cases reported from European countries (1).

Monkeypox is caused by Human monkeypox virus (MPXV), a double-stranded DNA virus of the family Poxviridae. It is a zoonotic virus, that spreads through respiratory droplets, direct contact or fomites. However, in the ongoing outbreak, the vast majority of cases have been reported in the context of sexual practices, affecting men who have sex with men (MSM), with no travel history to endemic areas (2).

We present the case of a 30-year-old male patient, MSM, diagnosed with HIV infection in December 2019. At the time of HIV diagnosis, he refused antiretroviral therapy (ART) and did not return to our practice. He returned in May 2022, when he started co-formulated Lamivudine and Dolutegravir, following collection of blood samples and exudates. When he began ART, he was asymptomatic and had a CD4 + T-cell count of 265 cells/ml (normal value 404- 1612 cells/ml), a CD4 + percentage of 10.20 % (normal value 33- 58 %) and an HIV viral load (VL) of 148.911 copies/mL.

Two weeks later, he started feeling unwell, with fever up to 39ºC, a headache and dizziness. The rapid influenza and SARS-CoV-2 screening tests were negative. Blood tests showed leukocytosis with white blood cell count of 12.790 cells/μL (normal value 3.900 - 10.200 cells/μL), absolute neutrophil count of 8.600 cells/μL (normal value 1.500 - 7.700 cells/μL) and a C-reactive protein level of 64.6 mg/L (normal value < 5). A positive Chlamydia Trachomatis (CT) NAAT was found in the rectal exudate on review of samples obtained at ART initiation.

The clinical picture was examined as an intercurrent viral infection. Thus, symptomatic treatment with paracetamol as well as doxycycline for CT rectal infection were prescribed.

However, the following day, the patient developed a non-pruriginous, generalized, maculopapular rash affecting mainly the trunk, buttocks, and upper and lower extremities. Skin examination revealed multiple well-demarcated purpuric macules with central umbilicated pustules and crusts (Fig. 1, A- D). There were no lesions on the mucous membranes or genital areas. Cervical lymph nodes were palpable.

Fig.1

Erythemato-purpuric rash mainly located on the back and buttocks of the patient (A). Detail of lesions on the left side of the back, showing small central pustules and erosions surrounded by erythemato-purpuric halo (B). Typical pustular lesion on the wrist (C). Papular lesion with central umbilication (D). Vacuolar interface dermatitis at the purpuric area showing empty vacuoles/bubbles along the basal layer (black triangles) with moderate superficial a middle perivascular lymphohistiocytic infiltrate (blue asterisks) and some isolated eosinophils (red arrow). The upper dermis contains prominent telangiectatic vessels -blue arrows- (E,F. Hematoxylin eosin staining -HE).

Although he did not meet refer sexual partners in the last four weeks or travel abroad (only mentioned a close dance in a nightclub), we assumed a suspected case of monkeypox infection. A viral swab was taken from a deroofed pustule in order to demonstrate MPXV DNA by a polymerase chain reaction (PCR) test. Hospital admission was not required. Thereupon, contact isolation at home and symptomatic treatment with paracetamol and a topic antibiotic were suggested. Monkeypox post-exposure prophylaxis was not considered in this case, as the patient did not declare to have been in close contact with a person testing positive for monkeypox infection.

Given that the purpuric exanthema and the temporal sequence could also suggest a drug reaction, we discontinued treatment with doxycycline and a skin punch-biopsy of a back skin lesion was performed.

The PCR test confirmed MPXV on the skin sample. The biopsy of the purpuric halo depicted an interface pattern with presence of basal cell vacuolization (hydropic degeneration) and perivascular lymphocytic infiltrate (superficial and middle dermis) with some isolated eosinophils (Fig.1, E-F). The area corresponding to the central pustule showed signs of folliculitis.

Five days later, the patient was asymptomatic with no new lesions and good recovery from the rash.

We present an atypical case of monkeypox infection in a patient with CDC Stage 2 HIV infection (265 CD4/ml), who had recently initiated ART. The clinical presentation consisted of an exuberant and generalized purpuric rash. There was no involvement of oral or genital areas, unlike the classic description of monkeypox lesions reported in other cases during the ongoing outbreak in Spain (3). A hypothesis of this particular case of non genital involvement could be the “close dance contact” referred by the patient.

Regarding the atypical hemorrhagic rash, we suggest that the fact that the patient’s HIV VL was still unsuppressed in combination with an impaired immune response, could have contributed to a more severe disease presentation. These factors may have led to a higher proliferation of the virus in the tissues following infection and, subsequently, to an increasing overflow of viruses into the blood stream. As MPXV causes a smallpox-like disease in humans, the clinical picture could be interpreted as a mild form of hemorrhagic smallpox-like presentation, similar to the one described in some patients with smallpox and increased viremia 50 years ago. This hemorrhagic variant of smallpox consisted of focal skin eruptions associated with petechial hemorrhages at the base of vesicles, but also into apparently normal skin between focal lesions, as the ones that appeared in our patient (4).

The possibility of immune reconstitution inflammatory syndrome (IRIS) was also assessed, given the recent initiation of ART. However, the patient did not have a CD4 + T-cell count below 200 cells/ml when he started ART, nor an AIDS-defining illness (all opportunistic infections were ruled out), and MPXV was not a pre-existing, but a supervening infection. IRIS was therefore dismissed, although immune restoration was underway. In fact, this newly initiated immune restoration may have generated a diminished response to the new infection, facilitating both transmission with less intense exposure and greater post-infection dissemination with the atypical manifestations.

Lastly, a drug reaction was initially suspected and pathological findings did not completely exclude this option. However, the hazard of a hypersensitivity reaction to doxycycline was highly unlikely, due to the complete recovery of the rash within a few days, without corticoid therapy. This clinical course suggests that the exanthema was more likely caused by the viral infection.

To our best knowledge, this kind of clinical and pathological presentation of monkeypox has not been previously reported.

Available data suggest that patients with advanced, uncontrolled HIV infection may be at increased risk for severe or prolonged monkeypox disease following infection (5).

Our patient had not yet achieved viral suppression at the time of monkeypox infection, which may have favoured a more extensive and atypical involvement, although this condition did not imply the need for hospital admission.

We suggest that monkeypox infection should be closely monitored in immunosuppressed patients and in those initiating ART, as it could trigger a more severe inflammatory response to the virus.

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All authors report no conflicts of interest relevant to this article. No external funding was received for this manuscript.

Author contributions

Simon-Gozalbo A and Gamo-Guerrero M wrote the main manuscript text. Alonso-Garcia S edited the images and reviewed the manuscript. Mauleon-Fernandez and Cuevas-Tascon G reviewed the manuscript.

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No external funding was received for this manuscript.

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All authors report no conflicts of interest relevant to this article.

Ethics Statement

Ethical review and approval was not required for this manuscript in accordance with the local legislation and institutional requirements. Written informed consent for the publication of images was obtained from the patient.